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Early onset or syndromic epilepsy v1.90 CACNA1B Louise Daugherty Added comment: Comment on publications: added publication to support gene-disease association
Early onset or syndromic epilepsy v1.90 CACNA1B Louise Daugherty Publications for gene: CACNA1B were set to
Early onset or syndromic epilepsy v1.89 PIGC Rebecca Foulger changed review comment from: PMID:27694521: Edvardson et al. 2017 studied 2 unrelated families (two siblings from a consanguineous Moslem-Arab parents, and a son of unrelated Sephardic-Jewish parents) who suffered from global DD, ID and seizures. PIGC variants were found: homozygous p.L189W in one family, and compound het variant (L212P/R21X) in another.; to: PMID:27694521: Edvardson et al. 2017 studied 2 unrelated families (two siblings from consanguineous Moslem-Arab parents, and a son of unrelated Sephardic-Jewish parents) who suffered from global DD, ID and seizures. PIGC variants were found: homozygous p.L189W in one family, and compound het variant (L212P/R21X) in another.
Early onset or syndromic epilepsy v1.89 PIGC Rebecca Foulger changed review comment from: PMID:27694521: Edvardson et al. 201x studied 2 unrelated families (two siblings from a consanguineous Moslem-Arab parents, and a son of unrelated Sephardic-Jewish parents) who suffered from global DD, ID and seizures. PIGC variants were found: homozygous p.L189W in one family, and compound het variant (L212P/R21X) in another.; to: PMID:27694521: Edvardson et al. 2017 studied 2 unrelated families (two siblings from a consanguineous Moslem-Arab parents, and a son of unrelated Sephardic-Jewish parents) who suffered from global DD, ID and seizures. PIGC variants were found: homozygous p.L189W in one family, and compound het variant (L212P/R21X) in another.
Early onset or syndromic epilepsy v1.89 PIGC Rebecca Foulger commented on gene: PIGC
Early onset or syndromic epilepsy v1.89 KIAA1109 Rebecca Foulger changed review comment from: Comment on list classification: Re-assessed gene:disease evidence based on 2019 paper (PMID:30906834). Kept rating as Amber awaiting further information: seizures present in 2 Lithuanian siblings (PMID:29290337) plus two African-American siblings (PMID:30906834). Plus Drosophila model. There is limited patient information because severe LOF alleles are incompatible with life.; to: Comment on list classification: Re-assessed gene:disease evidence based on 2019 paper (PMID:30906834). Kept rating as Amber awaiting further information: seizures present in 2 Lithuanian siblings (PMID:29290337) plus two African-American siblings (PMID:30906834). Plus Drosophila model (PMID:19640479). There is limited patient information because severe LOF alleles are incompatible with life.
Early onset or syndromic epilepsy v1.89 KIAA1109 Rebecca Foulger Classified gene: KIAA1109 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v1.89 KIAA1109 Rebecca Foulger Added comment: Comment on list classification: Re-assessed gene:disease evidence based on 2019 paper (PMID:30906834). Kept rating as Amber awaiting further information: seizures present in 2 Lithuanian siblings (PMID:29290337) plus two African-American siblings (PMID:30906834). Plus Drosophila model. There is limited patient information because severe LOF alleles are incompatible with life.
Early onset or syndromic epilepsy v1.89 KIAA1109 Rebecca Foulger Gene: kiaa1109 has been classified as Amber List (Moderate Evidence).
Undiagnosed metabolic disorders v1.116 HYAL1 Sarah Leigh Added comment: Comment on phenotypes: MPS IX, Natowicz (MPS IV, Morquio disease)
Undiagnosed metabolic disorders v1.116 HYAL1 Sarah Leigh Phenotypes for gene: HYAL1 were changed from MPS IX, Natowicz (MPS IV, Morquio disease); ?Mucopolysaccharidosis type IX, 601492 to ?Mucopolysaccharidosis type IX, 601492
Undiagnosed metabolic disorders v1.115 HYAL1 Sarah Leigh Publications for gene: HYAL1 were set to 27604308
Fetal anomalies v0.295 KIAA1109 Rebecca Foulger Publications for gene: KIAA1109 were set to 30485398; 29290337
Fetal anomalies v0.294 KIAA1109 Rebecca Foulger Added comment: Comment on mode of pathogenicity: The Mode of pathogenicity recorded in Gene2Phenotype for the disorder 'Brain atrophy, Dandy Walker and Contractures' is: All missense/in frame. However, as summarised in PMID:29290337 (Gueneau et al., 2018),
case subjects compatible with life carry missense variants but many of the more severely affected cases harbor homozygous or compound het truncating alleles. Therefore changed the Mode of pathogenicity back to default so LOF variants are captured.
Fetal anomalies v0.294 KIAA1109 Rebecca Foulger Mode of pathogenicity for gene: KIAA1109 was changed from Other to None
Fetal anomalies v0.293 KIAA1109 Rebecca Foulger Classified gene: KIAA1109 as Green List (high evidence)
Fetal anomalies v0.293 KIAA1109 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green after agreement from Anna de Burca (Genomics England clinical team). KIAA1109 is Green on the 'Hydrocephalus' and 'Arthrogryposis' panels. Sufficient cases in OMIM to support association with Alkuraya-Kucinskas syndrome (MIM:617822) which includes arthrogryposis and brain abnormalities: severe cases are incompatible with life. Multiple ultrasounds abnormalities reported in PMIDs 30485398 and 29290337.
Fetal anomalies v0.293 KIAA1109 Rebecca Foulger Gene: kiaa1109 has been classified as Green List (High Evidence).
Fetal anomalies v0.292 KIAA1109 Rebecca Foulger Publications for gene: KIAA1109 were set to 30485398
Fetal anomalies v0.291 KIAA1109 Rebecca Foulger Phenotypes for gene: KIAA1109 were changed from Brain atrophy, Dandy Walker and Contractures to Brain atrophy, Dandy Walker and Contractures; Alkuraya-Kucinskas syndrome, 617822
Fetal anomalies v0.290 KIAA1109 Rebecca Foulger commented on gene: KIAA1109: PMID:30485398: Filatova et al. 2019 report a Russian family with fetal anomalies detected upon ultrasound scans of three pregnancies. The first pregnancy resulted in a miscarriage. The second and third pregnancies were terminated because of ultrasound fetal abnormalities. In the third pregnancy, anomalies included bilateral ventriculomegaly, arthrogryposis (radial clubhand, bilateral clubfoot, flexed deformity of hip, knee and ankle joints), bilateral pyelectasis, increased thickness of the nuchal‐fold, hypoplastic and low set ears- Sanger sequencing revealed that the polymalformative fetus had compound heterozygous KIAA1109 variants. One of the dichorionic twins in the 4th pregnancy had similar phenotype and biallelic KIAA1109 variants (the healthy twin had only one variant c.1932‐3A>G).
Fetal anomalies v0.290 KIAA1109 Rebecca Foulger Mode of pathogenicity for gene: KIAA1109 was changed from to Other
Undiagnosed metabolic disorders v1.114 ARSG Sarah Leigh changed review comment from: Candidate gene for neuronal ceroid lipofuscinosis as reported in dogs and mice models (PubMed: 20679209, 22689975, 25452429, 26975023) and in a ; to: Candidate gene for neuronal ceroid lipofuscinosis as reported in dogs and mice models (PubMed: 20679209, 22689975, 25452429, 26975023) and in 5 affected members of 3 consanguineous Yemenite Jewish families (PMID 29300381).
Fetal anomalies v0.289 KIAA1109 Rebecca Foulger Publications for gene: KIAA1109 were set to
Early onset or syndromic epilepsy v1.88 KIAA1109 Rebecca Foulger Phenotypes for gene: KIAA1109 were changed from Alkuraya-Kucinskas syndrome 617822 to Alkuraya-Kucinskas syndrome 617822; seizures
Undiagnosed metabolic disorders v1.114 ARSG Sarah Leigh Mode of inheritance for gene: ARSG was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Undiagnosed metabolic disorders v1.113 ARSG Sarah Leigh Publications for gene: ARSG were set to 20679209; 25452429; 26975023; 29300381
Undiagnosed metabolic disorders v1.112 ARSG Sarah Leigh changed review comment from: Candidate gene for neuronal ceroid lipofuscinosis as reported in dogs and mice; to: Candidate gene for neuronal ceroid lipofuscinosis as reported in dogs and mice models (PubMed: 20679209, 22689975, 25452429, 26975023) and in a
Early onset or syndromic epilepsy v1.87 KIAA1109 Rebecca Foulger Publications for gene: KIAA1109 were set to 29290337; 19640479
Early onset or syndromic epilepsy v1.86 KIAA1109 Rebecca Foulger commented on gene: KIAA1109
Undiagnosed metabolic disorders v1.112 ARSG Sarah Leigh Added comment: Comment on phenotypes: Including neuronal ceroid lipofuscinosis
Undiagnosed metabolic disorders v1.112 ARSG Sarah Leigh Phenotypes for gene: ARSG were changed from neuronal ceroid lipofuscinosis to Usher syndrome, type IV 618144
Lysosomal storage disorder v0.6 ARSG Sarah Leigh Added comment: Comment on phenotypes: Including of neuronal ceroid lipofuscinosis
Lysosomal storage disorder v0.6 ARSG Sarah Leigh Phenotypes for gene: ARSG were changed from to Usher syndrome, type IV 618144
Lysosomal storage disorder v0.5 ARSG Sarah Leigh Publications for gene: ARSG were set to
Early onset or syndromic epilepsy v1.86 EFHC1 Rebecca Foulger Publications for gene: EFHC1 were set to 17159113; 18505993; 15258581; 19147686; 28370826
Early onset or syndromic epilepsy v1.85 EFHC1 Rebecca Foulger commented on gene: EFHC1: PMID:29750216: Thounaojam et al., 2017 studied 63 Indian patients from 63 independent families with Juvenile myoclonic epilepsy (JME) and found 4 heterozygous coding variants (R221C, R260Q, R294H and R244STOP) and 1 homozygous and one heterozygous coding variant (R159W, which is considered a polymorphism). Lack of family samples meant the mode of inheritance couldn't be followed up.
Early onset or syndromic epilepsy v1.85 EFHC1 Rebecca Foulger commented on gene: EFHC1: PMID:31056551: Heyne et al., 2019 performed a large-scale analysis of previously-sequenced variants in individuals with a 'neurodevelopmental disorder with epilepsy. They show that EFHC1 showed equal frequencies of ultra-rare variants in cases and controls supporting the existing evidence that EFHC1 may not be truly associated with epilepsy.
Early onset or syndromic epilepsy v1.85 EFHC1 Rebecca Foulger changed review comment from: PMID:28370826. Raju et al., 2017 examine 480 Juvenile myoclonic epilepsy patients from India, and identified 13 variants (11 of which were novel, 10 of which are predicted to be pathogenic) in 28 JME patients. They were absent or uncommon among controls. Patients with family histories of progressive myoclonic epilepsy (PME) were not included in the study. The authors submitted their variants to LOVD, including 14 polymorphisms that were common in controls and databases (https://databases.lovd.nl/shared/variants/EFHC1/unique).; to: PMID:28370826. Raju et al., 2017 examine 480 Juvenile myoclonic epilepsy patients from India, and identified 13 variants (11 of which were novel, 10 of which are predicted to be pathogenic) in 28 JME patients. They were absent or uncommon among controls. All variants were missense. Patients with family histories of progressive myoclonic epilepsy (PME) were not included in the study. The authors submitted their variants to LOVD, including 14 polymorphisms that were common in controls and databases (https://databases.lovd.nl/shared/variants/EFHC1/unique).
Early onset or syndromic epilepsy v1.85 EFHC1 Rebecca Foulger commented on gene: EFHC1
Familial hypercholesterolaemia v1.22 APOE Sarah Leigh Publications for gene: APOE were set to PMID: 23433584; 22949395; 26802169
Early onset or syndromic epilepsy v1.85 EFHC1 Rebecca Foulger Publications for gene: EFHC1 were set to 17159113; 18505993; 15258581; 19147686
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.123 RUNX2 Eleanor Williams changed review comment from: Loss of functional mutations associated with CLEIDOCRANIAL DYSPLASIA in Gene2Phenotype (confirmed).
In OMIM loss of function mutations are associated with several phenotypes including Cleidocranial dysplasia.
A heterozygous duplication of some exons of RUNX2 is associated with Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly . However, craniosynostosis is not listed as a feature of this disorder (PMID:  23290074, 25311905, 29891876

CNV EVIDENCE:

PMID: 20683987 - Mefford et al 2010 - Evaluated 186 individuals with single-suture craniosynostosis for submicroscopic deletions and duplications using whole-genome array CGH. They identified a heterozygous inverted 1.1 Mb duplication including the entire sequence of RUNX2, MIR586, and some of CLIC5 and SUPT3H in two affected cousins (1007 and 1019) with metopic synostosis and hypodontia. The duplication was inherited from the mother of one individual and it is presumed the father of the second individual (DNA not available, mother does not have the duplication). Both carrier parents have hypodontia by report, but neither is known to have had synostosis suggesting incomplete penetrance for that phenotype. The grandfather of 1007 and 1019 is described as having an abnormal head shape with a narrow forehead and several missing teeth; DNA was not available from this individual. They state that this CNV was not found in 2,493 control individuals [Itsara et al., 2009]. They compared RUNX2 expression levels in osteoblasts from these two individuals to expression levels in osteoblasts from unaffected individuals (n = 6) and individuals with synostosis but without duplication of RUNX2 (n = 22). The average expression of RUNX2 in the samples from the two individuals was higher than all affected and unaffected cell lines but it was not a statistically significant difference so should be interpreted with caution.

PMID: 23307468 - Varvagiannis et al 2013 - a girl with a de novo trisomy 6p12.3-p21.1 who showed craniosynostosis, manifested by the premature fusion of the right coronal and sagittal sutures, and also facial anomalies, psychomotor delay, and recurrent respiratory tract infections. MLPA analysis suggested a duplication of the entire RUNX2 gene. MLPA analysis indicated that the duplication was not present in parental blood samples. SNP array analysis identified the duplication was 6.9 Mb in size and mapped to 6p12.3–p21.1 (chr6: 40,797,975–47,701,961 NCBI Build 35; May 2004), thus encompassing 163 ENSEMBL genes. The finding of abnormal fontanelles and/or abnormal sutures, either manifested as craniosynostosis or not, has been documented in 5 cases in patients with pure partial trisomy 6p. No analysis of RUNX2 expression was performed.

PMID: 23348268 - Greives et al 2013 - present a case study of a boy with an atypical skull deformity with pan-craniosynostosis whose microarray analysis revealed 4 copies of a 1.24-Mb region from 6p12.3 to 6p21.1 containing the RUNX2 gene. He presented as an infant with airway obstruction from choanal atresia. He was diagnosed with a closed anterior fontanelle, ventricular septal defect, restricted range of motion in his elbows, mild conductive hearing loss, and developmental delays. They note that his multisutural craniosynostosis is the most extensive associated with RUNX2. No segregation analysis given.

PMID:25899668 - Molin et al 2015 - report on a family with an affected mother and three affected children. The four patients carried a 285 kb duplication identified by array comparative genomic hybridization. The duplication includes the entire sequence of RUNX2 and the 5' half of SUPT3H. We confirmed the duplication by real-time quantitative PCR in the four patients. Two children presented with the association of metopic craniosynostosis and oligo/hypodontia previously described, confirming the phenotype caused by RUNX2 duplication. The mother and one child had isolated hypodontia without craniosynostosis. The clinical presentation shown by syndromic patients IV‐1 and IV‐3 appears radically different from MDMHB, but shares a few similarities with previously duplication patients, including as hypodontia and craniosynostosis. Isolated hypodontia observed in Patients III‐2 and IV‐2 highlights a wider clinical spectrum associated with RUNX2 duplication, in addition to isolated and syndromic craniosynostosis and MDMHB.

Decipher - there are 6 patients with RUNX2 duplications over 1 kb in size. None mention craniosynostosis as a feature, although abnormality of the face/triangular face is listed for the patient with the 3.59 Mb duplication. https://decipher.sanger.ac.uk/gene/RUNX2#variants/RUNX2/patient-overlap/cnvs

Mouse models:

PMIDs: 11581292 (Liu et al 2001) and 12167715 (Geoffroy et al 2002) - both surprisingly report transgenic mice overexpressing Cbfa1 (runx2) developed severe osteopenia.

PMID: 21807129 - Maeno et al 2011 - report that in mice early onset of Runx2 expression in the cranial mesenchyme induced mineralization on E13.0, when no mineralization was observed in wild-type mice, and resulted in craniosynostosis.

PMID: 23300083 McGee-Lawrence et al 2013 - Runx2-deficient mice die at birth because of a lack of skeletal ossification. Axin2-deficient mice develop craniosynostosis because of high β-catenin activity. Runx2 represses transcription of Axin2 mRNA. They state that their data are consistent with the idea that Runx2 plays a central role in the etiologies of several different forms of craniosynostosis.

Control populations:
A search for the smallest CNV in a patient with craniosynostosis from Molin et al 2015 in the Database of Genomic Variants using GRCh38 coordinates shows no invidiuals from control populations with CNVs that cover RUNX2 http://dgv.tcag.ca/gb2/gbrowse/dgv2_hg38/?name=chr6%3A45265488-45551053;search=Search.

Summary:

Loss of function variants, partial duplication of the the RUNX2 gene and full duplication of the RUNX2 gene appear to result in different phenotypes. With regards to full duplication, there are 4 cases reported in separate publications of duplications fully covering the RUNX2 gene and patients with a craniosynostosis phenotype. The smallest duplication is 285 kb and includes RUNX2 and the 5' half of SUPT3H. However, there appears to be incomplete penetrance with some carriers having a less severe phenotype. Mefford et al state the CNV they report was not found in 2,493 control individuals and CNVs covering RUNX2 were not found in the Database of Genomics Variants. Mouse models give conflicting evidence. Mouse models of runx2 over-expression surprisingly found they developed severe osteopenia. However, early onset of Runx2 expression resulted in craniosynostosis, and Runx2 was found to repress Axin2, low levels of which can result in craniosynostosis. ; to: Loss of functional mutations associated with CLEIDOCRANIAL DYSPLASIA in Gene2Phenotype (confirmed).
In OMIM loss of function mutations are associated with several phenotypes including Cleidocranial dysplasia.
A heterozygous duplication of some exons of RUNX2 is associated with Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly . However, craniosynostosis is not listed as a feature of this disorder (PMID:  23290074, 25311905, 29891876)

CNV EVIDENCE:

PMID: 20683987 - Mefford et al 2010 - Evaluated 186 individuals with single-suture craniosynostosis for submicroscopic deletions and duplications using whole-genome array CGH. They identified a heterozygous inverted 1.1 Mb duplication including the entire sequence of RUNX2, MIR586, and some of CLIC5 and SUPT3H in two affected cousins (1007 and 1019) with metopic synostosis and hypodontia. The duplication was inherited from the mother of one individual and it is presumed the father of the second individual (DNA not available, mother does not have the duplication). Both carrier parents have hypodontia by report, but neither is known to have had synostosis suggesting incomplete penetrance for that phenotype. The grandfather of 1007 and 1019 is described as having an abnormal head shape with a narrow forehead and several missing teeth; DNA was not available from this individual. They state that this CNV was not found in 2,493 control individuals [Itsara et al., 2009]. They compared RUNX2 expression levels in osteoblasts from these two individuals to expression levels in osteoblasts from unaffected individuals (n = 6) and individuals with synostosis but without duplication of RUNX2 (n = 22). The average expression of RUNX2 in the samples from the two individuals was higher than all affected and unaffected cell lines but it was not a statistically significant difference so should be interpreted with caution.

PMID: 23307468 - Varvagiannis et al 2013 - a girl with a de novo trisomy 6p12.3-p21.1 who showed craniosynostosis, manifested by the premature fusion of the right coronal and sagittal sutures, and also facial anomalies, psychomotor delay, and recurrent respiratory tract infections. MLPA analysis suggested a duplication of the entire RUNX2 gene. MLPA analysis indicated that the duplication was not present in parental blood samples. SNP array analysis identified the duplication was 6.9 Mb in size and mapped to 6p12.3–p21.1 (chr6: 40,797,975–47,701,961 NCBI Build 35; May 2004), thus encompassing 163 ENSEMBL genes. The finding of abnormal fontanelles and/or abnormal sutures, either manifested as craniosynostosis or not, has been documented in 5 cases in patients with pure partial trisomy 6p. No analysis of RUNX2 expression was performed.

PMID: 23348268 - Greives et al 2013 - present a case study of a boy with an atypical skull deformity with pan-craniosynostosis whose microarray analysis revealed 4 copies of a 1.24-Mb region from 6p12.3 to 6p21.1 containing the RUNX2 gene. He presented as an infant with airway obstruction from choanal atresia. He was diagnosed with a closed anterior fontanelle, ventricular septal defect, restricted range of motion in his elbows, mild conductive hearing loss, and developmental delays. They note that his multisutural craniosynostosis is the most extensive associated with RUNX2. No segregation analysis given.

PMID:25899668 - Molin et al 2015 - report on a family with an affected mother and three affected children. The four patients carried a 285 kb duplication identified by array comparative genomic hybridization. The duplication includes the entire sequence of RUNX2 and the 5' half of SUPT3H. We confirmed the duplication by real-time quantitative PCR in the four patients. Two children presented with the association of metopic craniosynostosis and oligo/hypodontia previously described, confirming the phenotype caused by RUNX2 duplication. The mother and one child had isolated hypodontia without craniosynostosis. The clinical presentation shown by syndromic patients IV‐1 and IV‐3 appears radically different from MDMHB, but shares a few similarities with previously duplication patients, including as hypodontia and craniosynostosis. Isolated hypodontia observed in Patients III‐2 and IV‐2 highlights a wider clinical spectrum associated with RUNX2 duplication, in addition to isolated and syndromic craniosynostosis and MDMHB.

Decipher - there are 6 patients with RUNX2 duplications over 1 kb in size. None mention craniosynostosis as a feature, although abnormality of the face/triangular face is listed for the patient with the 3.59 Mb duplication. https://decipher.sanger.ac.uk/gene/RUNX2#variants/RUNX2/patient-overlap/cnvs

Mouse models:

PMIDs: 11581292 (Liu et al 2001) and 12167715 (Geoffroy et al 2002) - both surprisingly report transgenic mice overexpressing Cbfa1 (runx2) developed severe osteopenia.

PMID: 21807129 - Maeno et al 2011 - report that in mice early onset of Runx2 expression in the cranial mesenchyme induced mineralization on E13.0, when no mineralization was observed in wild-type mice, and resulted in craniosynostosis.

PMID: 23300083 McGee-Lawrence et al 2013 - Runx2-deficient mice die at birth because of a lack of skeletal ossification. Axin2-deficient mice develop craniosynostosis because of high β-catenin activity. Runx2 represses transcription of Axin2 mRNA. They state that their data are consistent with the idea that Runx2 plays a central role in the etiologies of several different forms of craniosynostosis.

Control populations:
A search for the smallest CNV in a patient with craniosynostosis from Molin et al 2015 in the Database of Genomic Variants using GRCh38 coordinates shows no invidiuals from control populations with CNVs that cover RUNX2 http://dgv.tcag.ca/gb2/gbrowse/dgv2_hg38/?name=chr6%3A45265488-45551053;search=Search.

Summary:

Loss of function variants, partial duplication of the the RUNX2 gene and full duplication of the RUNX2 gene appear to result in different phenotypes. With regards to full duplication, there are 4 cases reported in separate publications of duplications fully covering the RUNX2 gene and patients with a craniosynostosis phenotype. The smallest duplication is 285 kb and includes RUNX2 and the 5' half of SUPT3H. However, there appears to be incomplete penetrance with some carriers having a less severe phenotype. Mefford et al state the CNV they report was not found in 2,493 control individuals and CNVs covering RUNX2 were not found in the Database of Genomics Variants. Mouse models give conflicting evidence. Mouse models of runx2 over-expression surprisingly found they developed severe osteopenia. However, early onset of Runx2 expression resulted in craniosynostosis, and Runx2 was found to repress Axin2, low levels of which can result in craniosynostosis.
Inherited white matter disorders v1.69 ISCA2 Ivone Leong Classified gene: ISCA2 as Green List (high evidence)
Inherited white matter disorders v1.69 ISCA2 Ivone Leong Added comment: Comment on list classification: Promoted from red to green, based on evidence provided by expert reviewer and also advice from the Genomics England Clinical team.
Inherited white matter disorders v1.69 ISCA2 Ivone Leong Gene: isca2 has been classified as Green List (High Evidence).
Inherited white matter disorders v1.68 ISCA2 Ivone Leong Phenotypes for gene: ISCA2 were changed from to Multiple mitochondrial dysfunctions syndrome 4, 616370
Inherited white matter disorders v1.67 ISCA2 Ivone Leong Publications for gene: ISCA2 were set to 27564080; 25558065; 25539947; 22323289
Intellectual disability v2.927 ISCA2 Ivone Leong Classified gene: ISCA2 as Amber List (moderate evidence)
Intellectual disability v2.927 ISCA2 Ivone Leong Added comment: Comment on list classification: After consulting with the Genomics England Clinical team it was decided to only promote this gene to amber as the clinical picture is more of a mitochondrial phenotype and is likely to be investigated that way.
Intellectual disability v2.927 ISCA2 Ivone Leong Gene: isca2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v2.926 CWC27 Ivone Leong Classified gene: CWC27 as Green List (high evidence)
Intellectual disability v2.926 CWC27 Ivone Leong Added comment: Comment on list classification: Promoted from red to green. CWC27 is associated with a phenotype in OMIM and Gene2Phenotype. PMID: 28285769 reported on 7 unrelated families (10 affected individuals) with variants in this gene. 8/10 had neurological problems, which include ID, delayed walking, delayed speech or psychomotor retardation. Two cases (same family) are specified as moderate ID and they have indicated severe psychomotor retardation in others. After consulting the Genomics England Clinical Team, it was decided that there is enough evidence to promote this to green status.
Intellectual disability v2.926 CWC27 Ivone Leong Gene: cwc27 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v1.84 CUL4B Rebecca Foulger Classified gene: CUL4B as Amber List (moderate evidence)
Early onset or syndromic epilepsy v1.84 CUL4B Rebecca Foulger Added comment: Comment on list classification: Added CUL4B to the panel and rated Amber awaiting further clinical review. Seizures are noted in the literature in >30% of patients- although there are sufficient unrelated cases, the seizure phenotype is not consistent. Plus some of the cases recorded as seizures refer to febrile seizures, which are out of scope of this panel (e.g. PMID:17236139), and detailed information on seizures is not provided in most papers.
Early onset or syndromic epilepsy v1.84 CUL4B Rebecca Foulger Gene: cul4b has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v1.83 CUL4B Rebecca Foulger commented on gene: CUL4B: PMID:20014135: Isifor et al., 2010 report a de novo deletion of CUL4B in a boy with syndromic ID. Seizures were not reported.
Early onset or syndromic epilepsy v1.83 CUL4B Rebecca Foulger commented on gene: CUL4B: PMID:20002452: Badura-Stronka et al., 2010 report a CUL4B nonsense variant in 3 brothers with X-linked ID.
2 brothers had a single seizure, in the setting of infection. Therefore not appropriate in the context of this epilepsy panel.
Early onset or syndromic epilepsy v1.83 CUL4B Rebecca Foulger changed review comment from: PMID:17273978: Zou et al., 2007 analyse a previously reported (PMID:8135271) family (5 individuals) with X-linked ID and implicate p.R388X nonsense variant in CUL4B as the cause. 4/5 patients had seizures according to the summaries in PMID:20014135 and PMID:22182342; to: PMID:17273978: Zou et al., 2007 analyse a previously reported (PMID:8135271) family (5 individuals) with X-linked ID and implicate p.R388X nonsense variant in CUL4B as the cause. 4/5 patients had seizures according to the summaries in PMID:20014135 and PMID:22182342.
Early onset or syndromic epilepsy v1.83 CUL4B Rebecca Foulger commented on gene: CUL4B: PMID:17273978: Zou et al., 2007 analyse a previously reported (PMID:8135271) family (5 individuals) with X-linked ID and implicate p.R388X nonsense variant in CUL4B as the cause. 4/5 patients had seizures according to the summaries in PMID:20014135 and PMID:22182342
Early onset or syndromic epilepsy v1.83 CUL4B Rebecca Foulger commented on gene: CUL4B: PMID:22182342: Ravn et al., 2012 report a monozygotic Danish twin pair with a CUL4B deletion. Seizures is reported in both patients but no further details on the seizures are given. Ravn et al also summarise previous studies and note seizues in 14/22 patients. However this includes the febrile seizures noted in PMID:17236139 (Tarpet et al 2007).
Early onset or syndromic epilepsy v1.83 CUL4B Rebecca Foulger commented on gene: CUL4B: PMID:17236139: Tarpet et al., 2007 report CUL4B variants in 8/250 families with X-linked mental retardation. Segregation analysis is performed for all 8 families. Seizures (before age 2) reported in 8/11 affected males (Table 2). However the seizures are reported to be usually single febrile fits. The authors also note that further evidence is required to confirm that the missense variants are disease causing (e.g. in Family 432 it is possible that C638C>T (T213I) is a rare variant because ethically-matched controls were unavailable).
Early onset or syndromic epilepsy v1.83 CUL4B Rebecca Foulger commented on gene: CUL4B: PMID:25385192: Vulto-van Silfhout et al, 2015 identified CUL4B variants in 8/407 families with X-linked mental retardation. Plus CUL4B variants in an additional 3 patients (2 families) with malformations of cortical development. Ten different variants were identified in the 10 families (5 truncating, 2 splice, 1 in-frame deletion, 1 in-frame duplication, 1 missense). Across the 10 families with CUL4B variants, 7/22 (32%) of the individuals had seizures, though the phenotype was not always consistent between family members: In both family 1 (N151) and family 5 (D173), 1 of 3 individuals had seizures. The authors note that previously 17/30 (57%) of individuals with CUL4B variants were reported to have seizures.
Early onset or syndromic epilepsy v1.83 CUL4B Rebecca Foulger commented on gene: CUL4B: Seizures listed amongst the phenotypes of MENTAL RETARDATION SYNDROMIC X-LINKED CABEZAS TYPE in Gene2Phenotype. Seizures (onset <2 years) listed amongst the phenotypes in OMIM for Mental retardation, X-linked, syndromic 15 (Cabezas type), MIM:300354.
Early onset or syndromic epilepsy v1.83 CUL4B Rebecca Foulger Publications for gene: CUL4B were set to 25385192; 17236139
Early onset or syndromic epilepsy v1.82 CUL4B Rebecca Foulger gene: CUL4B was added
gene: CUL4B was added to Genetic epilepsy syndromes. Sources: NHS GMS,Literature
Mode of inheritance for gene: CUL4B was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: CUL4B were set to 25385192; 17236139
Phenotypes for gene: CUL4B were set to Mental retardation, X-linked, syndromic 15 (Cabezas type), 300354; seizures
Added comment: Added to Genetic epilepsy syndromes panel based on gene list submitted by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group.
Sources: NHS GMS, Literature
DDG2P v1.75 PCDH19 Rebecca Foulger Added comment: Comment on mode of inheritance: Note that the allelic requirement for PCDH19 in Gene2Phenotype is x-linked over-dominance. Note from Anna de Burca (Genomics England clinical team): PCDH19 only causes epilepsy in heterozygous females, and hemizygous males are unaffected. For the purposes of the pipeline, use 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease' to ensure that females with a variant are not missed.
DDG2P v1.75 PCDH19 Rebecca Foulger Mode of inheritance for gene: PCDH19 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)
Intellectual disability v2.925 TRAPPC12 Louise Daugherty changed review comment from: Comment on list classification: Appropriate phenotype, sufficient cases due to on unpublished report all support gene-disease association and relevance to this panel to rate gene to Green.; to: Comment on list classification: Appropriate phenotype, sufficient cases due to an unpublished report that supports gene-disease association and relevance to this panel to rate gene from Red to Green.
Intellectual disability v2.925 SMARCD1 Ivone Leong Publications for gene: SMARCD1 were set to 26350204
Intellectual disability v2.924 TRAPPC12 Louise Daugherty Classified gene: TRAPPC12 as Green List (high evidence)
Intellectual disability v2.924 TRAPPC12 Louise Daugherty Added comment: Comment on list classification: Appropriate phenotype, sufficient cases due to on unpublished report all support gene-disease association and relevance to this panel to rate gene to Green.
Intellectual disability v2.924 TRAPPC12 Louise Daugherty Gene: trappc12 has been classified as Green List (High Evidence).
Intellectual disability v2.923 TRAPPC12 Louise Daugherty Phenotypes for gene: TRAPPC12 were changed from Encephalopathy, progressive, early-onset, with brain atrophy and spasticity, 617669 to Encephalopathy, progressive, early-onset, with brain atrophy and spasticity, 617669; Developmental delay
Intellectual disability v2.922 TRAPPC12 Louise Daugherty Publications for gene: TRAPPC12 were set to 28777934
Intellectual disability v2.922 TRAPPC12 Louise Daugherty Phenotypes for gene: TRAPPC12 were changed from to Encephalopathy, progressive, early-onset, with brain atrophy and spasticity, 617669
Intellectual disability v2.921 TRAPPC12 Louise Daugherty Publications for gene: TRAPPC12 were set to
Intellectual disability v2.921 TRAPPC12 Louise Daugherty Mode of inheritance for gene: TRAPPC12 was changed from to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v2.920 TRAPPC12 Louise Daugherty reviewed gene: TRAPPC12: Rating: GREEN; Mode of pathogenicity: None; Publications: 28777934; Phenotypes: Encephalopathy, progressive, early-onset, with brain atrophy and spasticity, 617669; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v2.920 PPP3CA Ivone Leong Classified gene: PPP3CA as Green List (high evidence)
Intellectual disability v2.920 PPP3CA Ivone Leong Added comment: Comment on list classification: Promoted from red to green. PPP3CA is associated with Epileptic encephalopathy, infantile or early childhood, 1 in OMIM and is probably associated with Severe Neurodevelopmental Disease with Seizures
Page navigation in Gene2Phenotype. PMID: 28942967 reported on 6 unrelated individuals from different ethnic backgrounds who have different PPP3CA variants (missense and nonsense) who have severe ID. Therefore, there is enough evidence to promote this gene to green status.
Intellectual disability v2.920 PPP3CA Ivone Leong Gene: ppp3ca has been classified as Green List (High Evidence).
DDG2P v1.74 MN1 Rebecca Foulger commented on gene: MN1
DDG2P v1.74 EIF3F Rebecca Foulger commented on gene: EIF3F
DDG2P v1.74 BRD4 Rebecca Foulger commented on gene: BRD4
DDG2P v1.74 PCDH19 Rebecca Foulger Added comment: Comment on mode of inheritance: Changed Mode of Inheritance from 'x-linked over dominance' to a PanelApp standardised MOI term.
DDG2P v1.74 PCDH19 Rebecca Foulger Mode of inheritance for gene: PCDH19 was changed from x-linked over-dominance to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability v2.919 PPP3CA Ivone Leong Phenotypes for gene: PPP3CA were changed from Epileptic encephalopathy, infantile or early childhood, 1 to Epileptic encephalopathy, infantile or early childhood, 1, 617711
DDG2P v1.73 MN1 Rebecca Foulger gene: MN1 was added
gene: MN1 was added to DDG2P. Sources: DD-Gene2Phenotype,Expert Review Amber
Mode of inheritance for gene: MN1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MN1 were set to 21242494
Phenotypes for gene: MN1 were set to MN1 C-terminal truncation syndrome
DDG2P v1.73 EIF3F Rebecca Foulger gene: EIF3F was added
gene: EIF3F was added to DDG2P. Sources: DD-Gene2Phenotype,Expert Review Amber
Mode of inheritance for gene: EIF3F was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EIF3F were set to 30409806
Phenotypes for gene: EIF3F were set to EIF3F related developmental disorder
DDG2P v1.73 BRD4 Rebecca Foulger gene: BRD4 was added
gene: BRD4 was added to DDG2P. Sources: DD-Gene2Phenotype,Expert Review Amber
Mode of inheritance for gene: BRD4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: BRD4 were set to 29379197; 30302754
Phenotypes for gene: BRD4 were set to CORNELIA DE LANGE-LIKE SYNDROME
DDG2P v1.72 RAD51 Rebecca Foulger Classified gene: RAD51 as Red List (low evidence)
DDG2P v1.72 RAD51 Rebecca Foulger Added comment: Comment on list classification: Changed rating from Amber to Red to reflect a change in DD-G2P Disease confidence from probable to possible in June 2019. Disease remains as: MIRROR MOVEMENTS 2. Mode of inheritance remains as: monoallelic. Mode of pathogenicity remains as: loss of function.
DDG2P v1.72 RAD51 Rebecca Foulger Gene: rad51 has been classified as Red List (Low Evidence).
DDG2P v1.71 CHD3 Rebecca Foulger Phenotypes for gene: CHD3 were changed from Apraxia of speech to Macrocephaly and impaired speech and language
DDG2P v1.70 CHD3 Rebecca Foulger Added comment: Comment on publications: Added PMID:30397230 based on June 2019 DD-G2P update for CHD3. Removed PMID:29463886 as it is no longer listed as a reference in DD-G2P for CHD3.
DDG2P v1.70 CHD3 Rebecca Foulger Publications for gene: CHD3 were set to 29463886
DDG2P v1.69 CHD3 Rebecca Foulger Added comment: Comment on phenotypes: Replaced phenotype 'Apraxia of speech' with 'Macrocephaly and impaired speech and language' to reflect June 2019 DD-G2P update for CHD3. Disease confidence rating remains as: probable. Mode of inheritance remains as: monoallelic. Mode of pathogenicity remains as: all missense/in frame.
DDG2P v1.69 CHD3 Rebecca Foulger Phenotypes for gene: CHD3 were changed from Apraxia of speech to Apraxia of speech
Proteinuric renal disease v1.215 NUP133 Eleanor Williams Classified gene: NUP133 as Green List (high evidence)
Proteinuric renal disease v1.215 NUP133 Eleanor Williams Added comment: Comment on list classification: Following discussion with some members of the GMS Renal Specialist Test group on 2019-03-22 it was agreed that proteinuria is a relevant feature of Galloway-Mowat syndrome. Sufficient cases to rate green.
Proteinuric renal disease v1.215 NUP133 Eleanor Williams Gene: nup133 has been classified as Green List (High Evidence).
Proteinuric renal disease v1.214 WDR73 Eleanor Williams Mode of inheritance for gene: WDR73 was changed from to BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v1.213 WDR73 Eleanor Williams Classified gene: WDR73 as Green List (high evidence)
Proteinuric renal disease v1.213 WDR73 Eleanor Williams Added comment: Comment on list classification: Sufficient cases and GMS renal specialist test group decided Galloway-Mowat syndrome is appropriate for this panel
Proteinuric renal disease v1.213 WDR73 Eleanor Williams Gene: wdr73 has been classified as Green List (High Evidence).
IUGR and IGF abnormalities v1.26 AMMECR1 Julia Baptista changed review comment from: Basel-Vanagaite et al reported a boy with short stature (−3SD), low weight(−4SD), normal OFC (+1SD) and dysmorphic features (PMID: 28089922).

Maternal half-brothers reported by Andreoletti et al. (2017) also had short stature (below the 0.4th centile) and midface hypoplasia.

Short stature was also reported by Moyses-Oliveira et al in patients with loss-of-function AMMECR1 alleles due to nonsense variants, gene deletion and a translocation.; to: Basel-Vanagaite et al reported a boy with short stature (−3SD), low weight(−4SD), normal OFC (+1SD) and dysmorphic features (PMID: 28089922).

Maternal half-brothers reported by Andreoletti et al. (2017) also had short stature (below the 0.4th centile) and midface hypoplasia.

Short stature was also reported by Moyses-Oliveira et al in patients with loss-of-function AMMECR1 alleles due to nonsense variants, gene deletion and a translocation. (PMID: 29193635)
IUGR and IGF abnormalities v1.26 AMMECR1 Julia Baptista edited their review of gene: AMMECR1: Added comment: Basel-Vanagaite et al reported a boy with short stature (−3SD), low weight(−4SD), normal OFC (+1SD) and dysmorphic features (PMID: 28089922).

Maternal half-brothers reported by Andreoletti et al. (2017) also had short stature (below the 0.4th centile) and midface hypoplasia.

Short stature was also reported by Moyses-Oliveira et al in patients with loss-of-function AMMECR1 alleles due to nonsense variants, gene deletion and a translocation.; Changed publications: PMID: 29193635, 28089922, 27811305; Changed phenotypes: Short stature, midface hypoplasia, hearing impairment, elliptocytosis, nephrocalcinosis
IUGR and IGF abnormalities v1.26 AMMECR1 Julia Baptista gene: AMMECR1 was added
gene: AMMECR1 was added to IUGR and IGF abnormalities. Sources: Literature
Mode of inheritance for gene: AMMECR1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: AMMECR1 were set to Short stature; Midface hypoplasia, hearing impairment, elliptocytosis, and nephrocalcinosis
Review for gene: AMMECR1 was set to GREEN
Added comment: Sources: Literature
Intellectual disability v2.918 PPP1R15B Ivone Leong Classified gene: PPP1R15B as Green List (high evidence)
Intellectual disability v2.918 PPP1R15B Ivone Leong Added comment: Comment on list classification: Promoted from red to green. PPP1R15B is associated with a phenotype in OMIM and possibly associated with a phenotype in Gene2Phenotype. PMID: 26159176, 26307080 reported on 2 unrelated patients (Canadian, Algerian) who have the same missense variant in the PPP1R15B gene. Both patients have ID. PMID:27640355 reported on another case where the patient was compound heterozygous for 2 different variants (1 frameshift and 1 nonsense). The patient also had ID. Therefore, there is enough evidence to promote this gene to green status.
Intellectual disability v2.918 PPP1R15B Ivone Leong Gene: ppp1r15b has been classified as Green List (High Evidence).
Intellectual disability v2.917 PPP1R15B Ivone Leong Phenotypes for gene: PPP1R15B were changed from Microcephaly, short stature, and impaired glucose metabolism 2 to Microcephaly, short stature, and impaired glucose metabolism 2, 616817
Intellectual disability v2.916 PPP1R15B Ivone Leong Publications for gene: PPP1R15B were set to 26159176, 26307080, 27640355
Intellectual disability v2.915 PIGW Ivone Leong Classified gene: PIGW as Green List (high evidence)
Intellectual disability v2.915 PIGW Ivone Leong Added comment: Comment on list classification: Promoted from red to green, based the expert reviews and the evidence that was provided.
Intellectual disability v2.915 PIGW Ivone Leong Gene: pigw has been classified as Green List (High Evidence).
Intellectual disability v2.914 PIGW Ivone Leong Phenotypes for gene: PIGW were changed from Glycosylphosphatidylinositol biosynthesis defect 11 to Glycosylphosphatidylinositol biosynthesis defect 11, 616025
Intellectual disability v2.913 PIGW Ivone Leong Publications for gene: PIGW were set to 24367057, 27626616, 27626616
Intellectual disability v2.912 NDUFAF5 Ivone Leong Phenotypes for gene: NDUFAF5 were changed from Mitochondrial complex 1 deficiency to Mitochondrial complex 1 deficiency, 618238
Intellectual disability v2.911 MTFMT Ivone Leong Phenotypes for gene: MTFMT were changed from Combined oxidative phosphorylation deficiency 15 to Combined oxidative phosphorylation deficiency 15, 614947
Intellectual disability v2.910 NDUFAF5 Ivone Leong Publications for gene: NDUFAF5 were set to 19542079, 21607760, 18940309
Intellectual disability v2.909 MTFMT Ivone Leong Classified gene: MTFMT as Green List (high evidence)
Intellectual disability v2.909 MTFMT Ivone Leong Added comment: Comment on list classification: Promoted from red to green. MTFMT is associated with a phenotype in OMIM but not in Gene2Phenotype. There are >3 unrelated cases of patients who have different variants in this gene who have ID or developmental delay. Therefore, there is enough evidence to promote this gene to green status.
Intellectual disability v2.909 MTFMT Ivone Leong Gene: mtfmt has been classified as Green List (High Evidence).
Intellectual disability v2.908 MTFMT Ivone Leong Publications for gene: MTFMT were set to 24461907; 23499752
Intellectual disability v2.907 MTFMT Ivone Leong Publications for gene: MTFMT were set to 24461907; 23499752; 24461907
Intellectual disability v2.906 MTFMT Ivone Leong Publications for gene: MTFMT were set to 24461907, 23499752, 24461907
Intellectual disability v2.905 KMT5B Ivone Leong Publications for gene: KMT5B were set to 29276005, 28191889, 25363768
Early onset or syndromic epilepsy v1.81 CSNK2A1 Rebecca Foulger Classified gene: CSNK2A1 as Red List (low evidence)
Early onset or syndromic epilepsy v1.81 CSNK2A1 Rebecca Foulger Added comment: Comment on list classification: Rated CSNK2A1 as Red based on 1 paper (PMID:30655572) with 2 unrelated Japanese patients and de novo variants. Functional studies were not performed, and the seizures (and other features) were variable between the patients.
Early onset or syndromic epilepsy v1.81 CSNK2A1 Rebecca Foulger Gene: csnk2a1 has been classified as Red List (Low Evidence).
Early onset or syndromic epilepsy v1.80 CSNK2A1 Rebecca Foulger gene: CSNK2A1 was added
gene: CSNK2A1 was added to Genetic epilepsy syndromes. Sources: Literature
Mode of inheritance for gene: CSNK2A1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CSNK2A1 were set to 30655572
Phenotypes for gene: CSNK2A1 were set to seizures; Okur-Chung neurodevelopmental syndrome, 617062; CSNK2A1 syndrome
Review for gene: CSNK2A1 was set to AMBER
Added comment: Added CSNK2A1 to the epilepsy panel based on PMID:30655572. Nakashima et al, 2019 describe 4 patients with DD and seizures. Two of the patients (both Japanese) had de novo variants in CSNK2A1: c.593A>G, p.Lys198Arg in Patient 1, c.571C>T, p.Arg191* in Patient 2. Although both shared global DD and seizures, patient 1 showed later onset (4 yrs old) seizures which were less frequent. Additional features in Patient 1 include facial dysmorphisms, short stature and muscle weakness. Patient 2 had a more severe phenotype with seizures starting in the early infantile stage (5 months) with acute encephalopathy and death age 1 yr, 7 months. Note that Patient 1 had 3 candidate de novo deleterious variants (ATAD2B, TOPORS, CSNK2A1): ACMG variant guidelines were used to evaluate the pathogenicity of the variants. ATAD2B and TOPORS variants were likely pathogenic, and CSNK2A1 variant was pathogenic. In Patient 2, no further likely de novo variants were found.
Sources: Literature
Early onset or syndromic epilepsy v1.79 CSNK2B Rebecca Foulger Classified gene: CSNK2B as Green List (high evidence)
Early onset or syndromic epilepsy v1.79 CSNK2B Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green based on recent 2019 paper, PMID:30655572, which reports two further unrelated cases (Japanese and Malaysian) of de novo CSNK2B variants in patients with epilepsy. Although CSNK2B is still not associated with a disorder in OMIM or Gene2Phenotype, this takes the count from two to four cases (from 3 different papers) and is therefore sufficient for a Green rating on this panel.
Early onset or syndromic epilepsy v1.79 CSNK2B Rebecca Foulger Gene: csnk2b has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v1.78 CSNK2B Rebecca Foulger commented on gene: CSNK2B: PMID:30655572: Nakashima et al, 2019 describe 4 patients with ID, DD and seizures. Two of the patients had variants in CSNK2B: c.533_534insGT, p.(Pro179Tyrfs*49) in Malaysian Patient 3, and c.494A>G, p.(His165Arg) in Japanese Patient 4. Both had seizures within 2 months of age. Both variants occurred de novo. In each patient, only 1 likely candidate variant was proposed. Functional assays suggested that Pro179Tyrfs*49 mutant protein was produced but showed disrupted interaction with CSNK2A1.
Intellectual disability v2.904 CSNK2B Rebecca Foulger Deleted their comment
Intellectual disability v2.904 KLHL7 Ivone Leong Classified gene: KLHL7 as Green List (high evidence)
Intellectual disability v2.904 KLHL7 Ivone Leong Added comment: Comment on list classification: Promoted from red to green. KLHL7 is associated with Cold-induced sweating syndrome 3 (OMIM: 617055) in OMIM and Gene2Phenotype, but not BOS-like phenotype. There are 7 unrelated cases (PMID: 29074562, 30300710) from 5 unrelated families with affected individuals with BOS-like phenotype, global developmental delay and IUGR, who have different variants (nonsense, splicing and small deletions) in the KLHL7 gene.
There is also several cases (PMID: 30142437, being one reported case) of patients with variants in KLHL7 who have phenotypes that overlap Cold-induced sweating syndrome 3 and BOS-like phenotype. This patient also had global developmental delay and a variant different from those reported in PMID: 29074562, 30300710.

Therefore, there is enough evidence to promote this gene to green status.
Intellectual disability v2.904 KLHL7 Ivone Leong Gene: klhl7 has been classified as Green List (High Evidence).
Intellectual disability v2.903 CSNK2B Rebecca Foulger commented on gene: CSNK2B: PMID:30655572: Nakashima et al, 2019 describe 4 patients with ID, DD and seizures. Two of the patients had variants in CSNK2B: c.533_534insGT, p.(Pro179Tyrfs*49) in Malaysian Patient 3, and c.494A>G, p.(His165Arg) in Japanese Patient 4. Both had seizures within 2 months of age. Both variants occurred de novo. In each patient, only 1 likely candidate variant was proposed. Functional assays suggested that Pro179Tyrfs*49 mutant protein was produced but showed disrupted interaction with CSNK2A1.
Intellectual disability v2.903 CSNK2B Rebecca Foulger Publications for gene: CSNK2B were set to 28585349; 28762608
Intellectual disability v2.902 KLHL7 Ivone Leong Publications for gene: KLHL7 were set to 29074562
Early onset or syndromic epilepsy v1.78 CSNK2B Rebecca Foulger Publications for gene: CSNK2B were set to 28762608; 28585349; 27094248
Primary lymphoedema v1.81 SPRED1 Sarah Leigh Publications for gene: SPRED1 were set to
Primary lymphoedema v1.80 SPRED1 Sarah Leigh Classified gene: SPRED1 as Green List (high evidence)
Primary lymphoedema v1.80 SPRED1 Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.80 SPRED1 Sarah Leigh Gene: spred1 has been classified as Green List (High Evidence).
Primary lymphoedema v1.79 SOS2 Sarah Leigh Publications for gene: SOS2 were set to
Primary lymphoedema v1.78 SOS2 Sarah Leigh Classified gene: SOS2 as Green List (high evidence)
Primary lymphoedema v1.78 SOS2 Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.78 SOS2 Sarah Leigh Gene: sos2 has been classified as Green List (High Evidence).
Primary lymphoedema v1.77 SOS1 Sarah Leigh Publications for gene: SOS1 were set to
Primary lymphoedema v1.76 SOS1 Sarah Leigh Classified gene: SOS1 as Green List (high evidence)
Primary lymphoedema v1.76 SOS1 Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.76 SOS1 Sarah Leigh Gene: sos1 has been classified as Green List (High Evidence).
Primary lymphoedema v1.75 SHOC2 Sarah Leigh Publications for gene: SHOC2 were set to
Primary lymphoedema v1.74 SHOC2 Sarah Leigh Classified gene: SHOC2 as Green List (high evidence)
Primary lymphoedema v1.74 SHOC2 Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.74 SHOC2 Sarah Leigh Gene: shoc2 has been classified as Green List (High Evidence).
Primary lymphoedema v1.73 RIT1 Sarah Leigh Publications for gene: RIT1 were set to
Primary lymphoedema v1.72 RIT1 Sarah Leigh Classified gene: RIT1 as Green List (high evidence)
Primary lymphoedema v1.72 RIT1 Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.72 RIT1 Sarah Leigh Gene: rit1 has been classified as Green List (High Evidence).
Primary lymphoedema v1.71 RAF1 Sarah Leigh Publications for gene: RAF1 were set to
Primary lymphoedema v1.70 RAF1 Sarah Leigh Classified gene: RAF1 as Green List (high evidence)
Primary lymphoedema v1.70 RAF1 Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.70 RAF1 Sarah Leigh Gene: raf1 has been classified as Green List (High Evidence).
Primary lymphoedema v1.69 PTPN11 Sarah Leigh Publications for gene: PTPN11 were set to
Primary lymphoedema v1.68 PTPN11 Sarah Leigh Classified gene: PTPN11 as Green List (high evidence)
Primary lymphoedema v1.68 PTPN11 Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.68 PTPN11 Sarah Leigh Gene: ptpn11 has been classified as Green List (High Evidence).
Primary lymphoedema v1.67 PPP1CB Sarah Leigh Publications for gene: PPP1CB were set to
Primary lymphoedema v1.66 PPP1CB Sarah Leigh Classified gene: PPP1CB as Green List (high evidence)
Primary lymphoedema v1.66 PPP1CB Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.66 PPP1CB Sarah Leigh Gene: ppp1cb has been classified as Green List (High Evidence).
Primary lymphoedema v1.65 NRAS Sarah Leigh Publications for gene: NRAS were set to
Primary lymphoedema v1.64 NRAS Sarah Leigh Classified gene: NRAS as Green List (high evidence)
Primary lymphoedema v1.64 NRAS Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.64 NRAS Sarah Leigh Gene: nras has been classified as Green List (High Evidence).
Primary lymphoedema v1.63 NF1 Sarah Leigh Classified gene: NF1 as Green List (high evidence)
Primary lymphoedema v1.63 NF1 Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.63 NF1 Sarah Leigh Gene: nf1 has been classified as Green List (High Evidence).
Primary lymphoedema v1.62 NF1 Sarah Leigh Publications for gene: NF1 were set to
Primary lymphoedema v1.61 NF1 Sarah Leigh Classified gene: NF1 as Green List (high evidence)
Primary lymphoedema v1.61 NF1 Sarah Leigh Gene: nf1 has been classified as Green List (High Evidence).
Primary lymphoedema v1.60 MAP2K2 Sarah Leigh Publications for gene: MAP2K2 were set to
Primary lymphoedema v1.59 MAP2K2 Sarah Leigh Classified gene: MAP2K2 as Green List (high evidence)
Primary lymphoedema v1.59 MAP2K2 Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.59 MAP2K2 Sarah Leigh Gene: map2k2 has been classified as Green List (High Evidence).
Primary lymphoedema v1.58 MAP2K1 Sarah Leigh Publications for gene: MAP2K1 were set to
Primary lymphoedema v1.57 MAP2K1 Sarah Leigh Classified gene: MAP2K1 as Green List (high evidence)
Primary lymphoedema v1.57 MAP2K1 Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.57 MAP2K1 Sarah Leigh Gene: map2k1 has been classified as Green List (High Evidence).
Primary lymphoedema v1.56 LZTR1 Sarah Leigh Publications for gene: LZTR1 were set to
Primary lymphoedema v1.55 LZTR1 Sarah Leigh Classified gene: LZTR1 as Green List (high evidence)
Primary lymphoedema v1.55 LZTR1 Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.55 LZTR1 Sarah Leigh Gene: lztr1 has been classified as Green List (High Evidence).
Primary lymphoedema v1.54 KRAS Sarah Leigh Publications for gene: KRAS were set to
Primary lymphoedema v1.53 KRAS Sarah Leigh Classified gene: KRAS as Green List (high evidence)
Primary lymphoedema v1.53 KRAS Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.53 KRAS Sarah Leigh Gene: kras has been classified as Green List (High Evidence).
Primary lymphoedema v1.52 HRAS Sarah Leigh Publications for gene: HRAS were set to
Primary lymphoedema v1.51 HRAS Sarah Leigh Classified gene: HRAS as Green List (high evidence)
Primary lymphoedema v1.51 HRAS Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.51 HRAS Sarah Leigh Gene: hras has been classified as Green List (High Evidence).
Primary lymphoedema v1.50 CBL Sarah Leigh Classified gene: CBL as Green List (high evidence)
Primary lymphoedema v1.50 CBL Sarah Leigh Gene: cbl has been classified as Green List (High Evidence).
Primary lymphoedema v1.49 CBL Sarah Leigh Publications for gene: CBL were set to
Primary lymphoedema v1.48 CBL Sarah Leigh Classified gene: CBL as Red List (low evidence)
Primary lymphoedema v1.48 CBL Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.48 CBL Sarah Leigh Gene: cbl has been classified as Red List (Low Evidence).
Primary lymphoedema v1.47 BRAF Sarah Leigh Classified gene: BRAF as Green List (high evidence)
Primary lymphoedema v1.47 BRAF Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.47 BRAF Sarah Leigh Gene: braf has been classified as Green List (High Evidence).
Primary lymphoedema v1.46 BRAF Sarah Leigh Publications for gene: BRAF were set to
Primary lymphoedema v1.45 SPRED1 Sahar Mansour reviewed gene: SPRED1: Rating: GREEN; Mode of pathogenicity: ; Publications: 17704776, 19366998, 19443465, 21649642, 21548021; Phenotypes: Legius syndrome 611431; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.45 SOS2 Sahar Mansour reviewed gene: SOS2: Rating: GREEN; Mode of pathogenicity: ; Publications: 25795793, 26173643; Phenotypes: Noonan syndrome 9 616559; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.45 SOS1 Sahar Mansour reviewed gene: SOS1: Rating: GREEN; Mode of pathogenicity: ; Publications: 19438935, 17143285, 17143282, 17586837; Phenotypes: Noonan syndrome 4 610733; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.45 SHOC2 Sahar Mansour reviewed gene: SHOC2: Rating: GREEN; Mode of pathogenicity: ; Publications: 19684605, 22528146, 23918763; Phenotypes: Noonan-like syndrome with loose anagen hair 607721; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.45 RIT1 Sahar Mansour reviewed gene: RIT1: Rating: GREEN; Mode of pathogenicity: ; Publications: 23791108, 25124994, 24939608; Phenotypes: Noonan syndrome 8 615355; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.45 RAF1 Sahar Mansour reviewed gene: RAF1: Rating: GREEN; Mode of pathogenicity: ; Publications: 17603483, 17603482; Phenotypes: LEOPARD syndrome 2 611554, Noonan syndrome 5 611553; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.45 PTPN11 Sahar Mansour reviewed gene: PTPN11: Rating: GREEN; Mode of pathogenicity: ; Publications: 17603483, 11704759, 12529711, 12634870, 15384080, 15240615, 16263833, 17497712, 18678287; Phenotypes: LEOPARD syndrome 1 151100, Noonan syndrome 1 163950; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.45 PPP1CB Sahar Mansour reviewed gene: PPP1CB: Rating: GREEN; Mode of pathogenicity: ; Publications: 27264673, 28211982, 27681385; Phenotypes: Noonan syndrome-like disorder with loose anagen hair 2 617506; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.45 NRAS Sahar Mansour reviewed gene: NRAS: Rating: GREEN; Mode of pathogenicity: ; Publications: 19966803, 19775298; Phenotypes: Noonan syndrome 6 613224; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.45 NF1 Sahar Mansour reviewed gene: NF1: Rating: GREEN; Mode of pathogenicity: ; Publications: 16380919, 19845691, 12707950; Phenotypes: Neurofibromatosis-Noonan syndrome 601321, Neurofibromatosis, type 1 162200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.45 MAP2K2 Sahar Mansour reviewed gene: MAP2K2: Rating: GREEN; Mode of pathogenicity: ; Publications: 21396583, 23379592; Phenotypes: Cardiofaciocutaneous syndrome 4 615280; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.45 MAP2K1 Sahar Mansour reviewed gene: MAP2K1: Rating: GREEN; Mode of pathogenicity: ; Publications: 21396583, 23321623; Phenotypes: Cardiofaciocutaneous syndrome 3 615279; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.45 LZTR1 Sahar Mansour reviewed gene: LZTR1: Rating: GREEN; Mode of pathogenicity: ; Publications: 25795793, 29469822; Phenotypes: Noonan syndrome 10 616564 , Schwannomatosis-2, susceptibility to 615670; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Primary lymphoedema v1.45 KRAS Sahar Mansour reviewed gene: KRAS: Rating: GREEN; Mode of pathogenicity: ; Publications: 21396583; Phenotypes: Noonan syndrome 3 609942, Cardiofaciocutaneous syndrome 2 615278; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.45 HRAS Sahar Mansour reviewed gene: HRAS: Rating: GREEN; Mode of pathogenicity: ; Publications: 16170316, 16969868, 16443854, 21396583; Phenotypes: Costello syndrome 218040; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.45 CBL Sahar Mansour reviewed gene: CBL: Rating: GREEN; Mode of pathogenicity: ; Publications: 20619386, 20543203, 19571318; Phenotypes: Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia 613563 ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.45 BRAF Sahar Mansour reviewed gene: BRAF: Rating: GREEN; Mode of pathogenicity: ; Publications: 19206169, 21396583; Phenotypes: LEOPARD syndrome 3 613707, Cardiofaciocutaneous syndrome 115150, Noonan syndrome 7 613706; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.44 SPRED1 Sarah Leigh gene: SPRED1 was added
gene: SPRED1 was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: SPRED1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: SPRED1 were set to Legius syndrome 611431
Primary lymphoedema v1.44 SOS2 Sarah Leigh gene: SOS2 was added
gene: SOS2 was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: SOS2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: SOS2 were set to Noonan syndrome 9 616559
Mode of pathogenicity for gene: SOS2 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments
Primary lymphoedema v1.44 SOS1 Sarah Leigh gene: SOS1 was added
gene: SOS1 was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: SOS1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: SOS1 were set to Noonan syndrome 4 610733
Mode of pathogenicity for gene: SOS1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments
Primary lymphoedema v1.44 SHOC2 Sarah Leigh gene: SHOC2 was added
gene: SHOC2 was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: SHOC2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: SHOC2 were set to Noonan-like syndrome with loose anagen hair 607721
Primary lymphoedema v1.44 RIT1 Sarah Leigh gene: RIT1 was added
gene: RIT1 was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: RIT1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: RIT1 were set to Noonan syndrome 8 615355
Mode of pathogenicity for gene: RIT1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments
Primary lymphoedema v1.44 RAF1 Sarah Leigh gene: RAF1 was added
gene: RAF1 was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: RAF1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: RAF1 were set to Noonan syndrome 5 611553; LEOPARD syndrome 2 611554
Mode of pathogenicity for gene: RAF1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments
Primary lymphoedema v1.44 PTPN11 Sarah Leigh gene: PTPN11 was added
gene: PTPN11 was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: PTPN11 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: PTPN11 were set to Noonan syndrome 1 163950; LEOPARD syndrome 1 151100
Mode of pathogenicity for gene: PTPN11 was set to Other - please provide details in the comments
Primary lymphoedema v1.44 PPP1CB Sarah Leigh gene: PPP1CB was added
gene: PPP1CB was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: PPP1CB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: PPP1CB were set to Noonan syndrome-like disorder with loose anagen hair 2 617506
Primary lymphoedema v1.44 NRAS Sarah Leigh gene: NRAS was added
gene: NRAS was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: NRAS was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: NRAS were set to Noonan syndrome 6 613224
Mode of pathogenicity for gene: NRAS was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments
Primary lymphoedema v1.44 NF1 Sarah Leigh gene: NF1 was added
gene: NF1 was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: NF1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: NF1 were set to Neurofibromatosis-Noonan syndrome 601321; Neurofibromatosis, type 1 162200
Primary lymphoedema v1.44 MAP2K2 Sarah Leigh gene: MAP2K2 was added
gene: MAP2K2 was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: MAP2K2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: MAP2K2 were set to Cardiofaciocutaneous syndrome 4 615280
Mode of pathogenicity for gene: MAP2K2 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments
Primary lymphoedema v1.44 MAP2K1 Sarah Leigh gene: MAP2K1 was added
gene: MAP2K1 was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: MAP2K1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: MAP2K1 were set to Cardiofaciocutaneous syndrome 3 615279
Mode of pathogenicity for gene: MAP2K1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments
Primary lymphoedema v1.44 LZTR1 Sarah Leigh gene: LZTR1 was added
gene: LZTR1 was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: LZTR1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: LZTR1 were set to Schwannomatosis-2, susceptibility to 615670; Noonan syndrome 10 616564
Primary lymphoedema v1.44 KRAS Sarah Leigh gene: KRAS was added
gene: KRAS was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: KRAS was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: KRAS were set to Noonan syndrome 3 609942; Cardiofaciocutaneous syndrome 2 615278
Mode of pathogenicity for gene: KRAS was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments
Primary lymphoedema v1.44 HRAS Sarah Leigh gene: HRAS was added
gene: HRAS was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: HRAS was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: HRAS were set to Costello syndrome 218040
Mode of pathogenicity for gene: HRAS was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments
Primary lymphoedema v1.44 CBL Sarah Leigh gene: CBL was added
gene: CBL was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: CBL was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: CBL were set to Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia 613563
Mode of pathogenicity for gene: CBL was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments
Primary lymphoedema v1.44 BRAF Sarah Leigh gene: BRAF was added
gene: BRAF was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: BRAF was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: BRAF were set to LEOPARD syndrome 3 613707; Noonan syndrome 7 613706; Cardiofaciocutaneous syndrome 115150
Mode of pathogenicity for gene: BRAF was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments
Intellectual disability v2.901 TCF20 Eleanor Williams Added comment: Comment on phenotypes: Updated as phenotype added to OMIM in May 2019
Intellectual disability v2.901 TCF20 Eleanor Williams Phenotypes for gene: TCF20 were changed from TCF20 syndrome; Intellectual disability; developmental delay to TCF20 syndrome; Intellectual disability; developmental delay; Developmental delay with variable intellectual impairment and behavioral abnormalities 618430
Fetal anomalies v0.288 TCF20 Eleanor Williams Added comment: Comment on phenotypes: updated as phenotype added to OMIM in May 2019
Fetal anomalies v0.288 TCF20 Eleanor Williams Phenotypes for gene: TCF20 were changed from TCF20 syndrome to TCF20 syndrome; Developmental delay with variable intellectual impairment and behavioral abnormalities 618430
Possible mitochondrial disorder, nuclear genes v0.204 SLC25A42 Eleanor Williams Added comment: Comment on phenotypes: Updated as phenotype added to OMIM in May 2019.
Possible mitochondrial disorder, nuclear genes v0.204 SLC25A42 Eleanor Williams Phenotypes for gene: SLC25A42 were changed from No OMIM phenotype to Metabolic crises, recurrent, with variable encephalomyopathic features and neurologic regression, 618416
Neurodegenerative disorders, adult onset v1.49 ATXN7 Louise Daugherty changed review comment from: This gene was uploaded from the curation template sent out to the GLHs for GMS Neurology specialist test group as it is a RED gene on the Neurodegenerative disorders - adult onset panel. The GREEN review from James Polke (Neurogenetics Laboratory, Institute of Neurology, London) is likely to relate to the STR ATXN7_CAG and not the gene entity, as there are no SNVsfor this gene being associated to the disorder, this gene is rated RED.; to: This gene was uploaded from the curation template sent out to the GLHs for GMS Neurology specialist test group as it is a RED gene on the Hereditary ataxia panel. The GREEN review from James Polke (Neurogenetics Laboratory, Institute of Neurology, London) is likely to relate to the STR ATXN7_CAG and not the gene entity, but this needs to be checked during the Neurology test Group call July 2019
Possible mitochondrial disorder, nuclear genes v0.203 PARS2 Eleanor Williams Added comment: Comment on phenotypes: Phenotype added to OMIM in May 2019
Possible mitochondrial disorder, nuclear genes v0.203 PARS2 Eleanor Williams Phenotypes for gene: PARS2 were changed from Infantile-onset encephalopathy; Alpers syndrome; Infantile-onset neurodegenerative disorder to Infantile-onset encephalopathy; Alpers syndrome; Infantile-onset neurodegenerative disorder; Epileptic encephalopathy, early infantile, 75, 61843
Mitochondrial disorders v1.401 PARS2 Eleanor Williams Added comment: Comment on phenotypes: Phenotype added to OMIM in May 2019
Mitochondrial disorders v1.401 PARS2 Eleanor Williams Phenotypes for gene: PARS2 were changed from Multiple respiratory chain complex deficiencies (disorders of protein synthesis); No OMIM phenotype; Alpers syndrome. to Multiple respiratory chain complex deficiencies (disorders of protein synthesis); No OMIM phenotype; Alpers syndrome; Epileptic encephalopathy, early infantile, 75, 618437
Hereditary ataxia, adult onset v1.174 MAPK8IP3 Eleanor Williams commented on gene: MAPK8IP3
Hereditary ataxia, adult onset v1.174 MAPK8IP3 Eleanor Williams Phenotypes for gene: MAPK8IP3 were changed from Intellectual Disability with variable brain anomalies to Intellectual Disability with variable brain anomalies; Neurodevelopmental disorder with or without variable brain abnormalities, 618443
Neurodegenerative disorders, adult onset v1.49 ATXN7 Louise Daugherty commented on gene: ATXN7: This gene was uploaded from the curation template sent out to the GLHs for GMS Neurology specialist test group as it is a RED gene on the Neurodegenerative disorders - adult onset panel. The GREEN review from James Polke (Neurogenetics Laboratory, Institute of Neurology, London) is likely to relate to the STR ATXN7_CAG and not the gene entity, as there are no SNVsfor this gene being associated to the disorder, this gene is rated RED.
Intellectual disability v2.900 KIF14 Ivone Leong Classified gene: KIF14 as Green List (high evidence)
Intellectual disability v2.900 KIF14 Ivone Leong Added comment: Comment on list classification: Promoted from red to green. KIF14 is associated with a phenotype in OMIM but not in Gene2Phenotype. PMID: 29343805, 28892560 reported on 7 unrelated families with affected members who have moderate to severe ID and have different variants in KIF14. Therefore, there is enough evidence to promote this gene to green status.
Intellectual disability v2.900 KIF14 Ivone Leong Gene: kif14 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v1.77 CNPY3 Rebecca Foulger Classified gene: CNPY3 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v1.77 CNPY3 Rebecca Foulger Added comment: Comment on list classification: Re-reviewed gene:disease association for CNPY3 during curation of GMS panel. Amber rating is still appropriate: Probable Disease confidence rating in DD-G2P for EARLY ONSET EPILEPTIC ENCEPHALOPATHY, and literature evidence remains at 3 patients from 2 unrelated families from one paper (PMID:29394991) with limited segregation data from one of the families.
Early onset or syndromic epilepsy v1.77 CNPY3 Rebecca Foulger Gene: cnpy3 has been classified as Amber List (Moderate Evidence).
Intellectual disability v2.899 KIF14 Ivone Leong Publications for gene: KIF14 were set to 29343805, 28892560
Early onset or syndromic epilepsy v1.76 CNPY3 Rebecca Foulger commented on gene: CNPY3
Intellectual disability v2.898 MAPK8IP3 Eleanor Williams Added comment: Comment on phenotypes: OMIM phenotype recently added to OMIM
Intellectual disability v2.898 MAPK8IP3 Eleanor Williams Phenotypes for gene: MAPK8IP3 were changed from Abnormal muscle tone; Global developmental delay; Intellectual disability; Abnormality of nervous system morphology; No OMIM number to Abnormal muscle tone; Global developmental delay; Intellectual disability; Abnormality of nervous system morphology; Neurodevelopmental disorder with or without variable brain abnormalities, 618443
Early onset or syndromic epilepsy v1.76 ASAH1 Rebecca Foulger Publications for gene: ASAH1 were set to 29169047; 22703880; 24164096; 30291339; 27026573
Early onset or syndromic epilepsy v1.75 ASAH1 Rebecca Foulger Classified gene: ASAH1 as Green List (high evidence)
Early onset or syndromic epilepsy v1.75 ASAH1 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Red to Green. Confirmed Disease confidence rating in Gene2Phenotype for SPINAL MUSCULAR ATROPHY ASSOCIATED WITH PROGRESSIVE MYOCLONIC EPILEPSY. Relevant disorder in OMIM (Spinal muscular atrophy with progressive myoclonic epilepsy, 159950). Although the three families reported in PMID:22703880 share a haplotype suggesting Founder effect, there are sufficient additional papers reporting cases with additional variants. Note that although most individuals report muscle weakness followed by seizures, PMIDs 27026573 and 30291339 report muscle weakness WITHOUT epilepsy, and PMID:24164096 also report a case with seizures without muscle weakness- there is therefore some heterogeneity in the phenotype. On balance there are plenty of literature reports of seizures in patients with biallelic ASAH1 variants for inclusion on this panel.
Early onset or syndromic epilepsy v1.75 ASAH1 Rebecca Foulger Gene: asah1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v1.74 ASAH1 Rebecca Foulger commented on gene: ASAH1: Additional cases of seizures associated with SMA were reported in papers including PMIDs 27723502, 26526000, 25847462, 25578555, 31216804.
Early onset or syndromic epilepsy v1.74 ASAH1 Rebecca Foulger commented on gene: ASAH1: PMID:27723502 (Oguz et al, 2016) report eyelid myoclonic status epilepticus as an unusual manifestation of SMA-PME in a Turkish girl of consanguineous parents. Ambulatory problems were noted age 4. Generalized seizures developed later.
Early onset or syndromic epilepsy v1.74 ASAH1 Rebecca Foulger commented on gene: ASAH1: PMID:29169047: Yidiz et al (2018) report a 13.5 yr old girl with SMA-PME. She was the 8th child born of consanguineous parents. She presented with progressive muscle weakiness age 10, tremor, seizure (generalized epilepsy) and decreased cognitive functions. Screening revelead homozygous missense variant c.173C>T (T58M). The parents or siblings were not tested.
Intellectual disability v2.897 KIF14 Ivone Leong Phenotypes for gene: KIF14 were changed from Microcephaly 20, primary, autosomal recessive to Microcephaly 20, primary, autosomal recessive, 617914
Intellectual disability v2.896 KCTD3 Ivone Leong Publications for gene: KCTD3 were set to 29406573, 27848944, 25558065
Intellectual disability v2.895 KCTD3 Ivone Leong Phenotypes for gene: KCTD3 were changed from to Epilepsy and global developmental delay
Intellectual disability v2.894 KCTD3 Ivone Leong Classified gene: KCTD3 as Green List (high evidence)
Intellectual disability v2.894 KCTD3 Ivone Leong Added comment: Comment on list classification: Promoted from amber to green. No phenotypes are associated with this gene OMIM or Gene2Phenotype.
One study (PMID: 29406573) reported different variants in KCTD3 for 7 probands from 4 consanguineous families who all have epilepsy and global developmental disability. The families are from the same geographical location. The study did show that the variants segregated with the phenotype. Two other large (PMID: 27848944, 25558065) screening studies reported 2 probands with the same frameshift KCTD3 variant who have epilepsy and global developmental disability. This frameshift variant was also found in one of the probands in PMID: 29406573 article.
Intellectual disability v2.894 KCTD3 Ivone Leong Gene: kctd3 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v1.74 ASAH1 Rebecca Foulger changed review comment from: PMID:30291339: Ame van der Beek et al (2019) report an additional case of a mild SMA phenotype with NO myoclonic epilepsy due to variants in ASAH1. Ambulatory problems of the 24 year old female began around age 8 years.; to: PMID:30291339: Ame van der Beek et al (2019) report an additional case of a mild SMA phenotype with NO myoclonic epilepsy due to variants in ASAH1. She carried two novel ASAH1 variants (Pro26Arg and c.125+1G>A splice variant leading to an unstable transcript lacking exon 2. Segregation analysis confirmed the parental inheritance and acid ceramidase activity was deficient in functional tests.
Early onset or syndromic epilepsy v1.74 ASAH1 Rebecca Foulger Publications for gene: ASAH1 were set to 29169047; 22703880; 24164096
Early onset or syndromic epilepsy v1.73 ASAH1 Rebecca Foulger commented on gene: ASAH1: PMID:30291339: Ame van der Beek et al (2019) report an additional case of a mild SMA phenotype with NO myoclonic epilepsy due to variants in ASAH1. Ambulatory problems of the 24 year old female began around age 8 years.
Early onset or syndromic epilepsy v1.73 ASAH1 Rebecca Foulger commented on gene: ASAH1: PMID:27026573: Filosto et al., 2016 studied 2 subjects: a 30yr old pregnant woman and her 17 year old sister affected with slowly progressive SMA since childhood but in the ABSENCE of siezures. Both subjects had a homozygous c.124A>G (T42A) variant in ASAH1.
Early onset or syndromic epilepsy v1.73 ASAH1 Rebecca Foulger commented on gene: ASAH1: PMID:24164096: In a girl who presented with absence and atonic seizures age 10, Dyment et al. (2014) identified compound heterozygous mutations in the ASAH1 gene: c.850G>T (G284X) and c.456A>C. Each parent was found to carry one of the variants. Although c.456A>C is predicted to encode a Lys152Asn substitution, it is 2bp away from a splice donor site and fibroblast assays showed an absence of exon 6, suggesting abberant splicing. Note that the patient harboured several hundred rare variants with at least two rare non-synonymous variants within the coding sequence of 4 genes (ASAH1, OC90, CACNA1C and LAMA5) though CACNA1C and OC90 were ruled out because the variants were found to be inherited from a single parent. Unlike the cases from PMID:22703880, this patient presented with seizures as the first symptom, and displayed no significant muscle weakness.
Early onset or syndromic epilepsy v1.73 ASAH1 Rebecca Foulger commented on gene: ASAH1
Intellectual disability v2.893 ISCA2 Ivone Leong Tag founder-effect tag was added to gene: ISCA2.
Intellectual disability v2.893 GEMIN4 Ivone Leong Tag founder-effect tag was added to gene: GEMIN4.
Early onset or syndromic epilepsy v1.73 ASAH1 Rebecca Foulger Mode of inheritance for gene: ASAH1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v1.72 ASAH1 Rebecca Foulger Phenotypes for gene: ASAH1 were changed from to Spinal muscular atrophy with progressive myoclonic epilepsy, 159950
Intellectual disability v2.893 ITPA Ivone Leong Classified gene: ITPA as Green List (high evidence)
Intellectual disability v2.893 ITPA Ivone Leong Added comment: Comment on list classification: Promoted from red to green. ITPA is associated with a phenotype in OMIM but not in Gene2Phenotype. There are 5 unrelated families (PMID: 26224535, 30816001) with affected individuals who have global developmental delay with different variants in ITPA. PMID: 19498443 describes a knockout mouse model of Itpa, which had growth retardation. Therefore, there is enough evidence to promote this gene to green status.
Intellectual disability v2.893 ITPA Ivone Leong Gene: itpa has been classified as Green List (High Evidence).
Intellectual disability v2.892 ITPA Ivone Leong Publications for gene: ITPA were set to 26224535; 30816001
Intellectual disability v2.891 ITPA Ivone Leong Publications for gene: ITPA were set to 26224535; 30816001
Intellectual disability v2.891 ITPA Ivone Leong Publications for gene: ITPA were set to 26224535; 30816001
Intellectual disability v2.891 ITPA Ivone Leong Publications for gene: ITPA were set to 26224535
Unexplained kidney failure in young people v1.71 GLA Eleanor Williams Classified gene: GLA as Green List (high evidence)
Unexplained kidney failure in young people v1.71 GLA Eleanor Williams Added comment: Comment on list classification: After consultation with the Genomics England clinical team it was decided to rate this gene green on the 100K panel.
Unexplained kidney failure in young people v1.71 GLA Eleanor Williams Gene: gla has been classified as Green List (High Evidence).
Unexplained kidney failure in young people v1.70 GLA Eleanor Williams Phenotypes for gene: GLA were changed from to renal insufficiency; renal failure; Fabry disease, 301500
Unexplained kidney failure in young people v1.69 GLA Eleanor Williams Publications for gene: GLA were set to
Unexplained kidney failure in young people v1.68 GLA Eleanor Williams changed review comment from: This gene has been reviewed by Daniel Gale on the Unexplained paediatric onset end-stage renal disease panel 2019-05-08.; to: This gene has been reviewed by Daniel Gale on the Unexplained paediatric onset end-stage renal disease panel 2019-05-08. He states that "Fabry disease may present with renal limited disease, including presentation at end stage renal failure with no other clinical features (typically in young adults in their 20s). This has been repeatedly described in cohorts of people with kidney failure, ascertained either using biochemical or genetic screening."
Unexplained kidney failure in young people v1.68 GLA Eleanor Williams commented on gene: GLA: GLA is associated with Fabry disease (#301500) in OMIM

PMID: 28006774 - Turkmen et al 2016 - 3 out of 313 chronic kidney disease patients not receiving renal replacement therapy (0.95%) were diagnosed of Fabry disease by GLA gene mutation analysis. The age of the patients and their family members with Fabry disease ( total number =11) was 41.3 +/- 14.5.

PMID: 15861341 - Cybulla et al 2005 - describe a family presenting with chronic renal failure and proteinuria in which classic skin and neurological features were absent and the diagnosis of Fabry disease was difficult and not established until a second family member developed renal abnormalities. The index patient was 35 years old. Analysis of the alpha-GLA gene showed the mutation E66K. The mutation also was found in another asymptomatic 30-year-old brother who also had chronic renal failure and proteinuria, but normal extrarenal findings. Mutation carriers also included the mother, a sister (both without abnormalities), and a nephew (with episodic pains in his feet).

PMID: 15100373 - Kotanko et al 2004 - Nationwide screening of Anderson-Fabry disease among dialysis patients in Austria. Individuals with decreased leukocyte AGAL activity were subjected to mutation testing in the GLA gene, Genetic testing revealed mutations associated with Fabry disease in all four men with severely decreased AGAL activity resulting in a prevalence of 0.161% for the entire study population. Age at start of dialysis ranged from 27 to 53.
Unexplained kidney failure in young people v1.68 GLA Eleanor Williams commented on gene: GLA
Rare multisystem ciliopathy disorders v1.115 POC1B Eleanor Williams changed review comment from: Amber rating confirmed with the Genomics England rare disease clinical team.; to: Amber rating confirmed with the Genomics England rare disease clinical team. This appears to be a single organ presentation of a disorder affecting cilia. It is appropriately green on the retinal disorders panel.
Rare multisystem ciliopathy disorders v1.115 POC1B Eleanor Williams commented on gene: POC1B: Amber rating confirmed with the Genomics England rare disease clinical team.
Hereditary haemorrhagic telangiectasia v1.49 EPHB4 Louise Daugherty Classified gene: EPHB4 as Green List (high evidence)
Hereditary haemorrhagic telangiectasia v1.49 EPHB4 Louise Daugherty Added comment: Comment on list classification: Changed from Amber to Green. Appropriate phenotype, sufficient cases and external expert review all support gene-disease association and relevance to this panel to rate gene as Green.
Hereditary haemorrhagic telangiectasia v1.49 EPHB4 Louise Daugherty Gene: ephb4 has been classified as Green List (High Evidence).
Rare multisystem ciliopathy disorders v1.115 LBR Eleanor Williams commented on gene: LBR: The Genomics England rare disease clinical team feedback is that the phenotype described to date (apart from polydactyly) does not strongly suggest a multi-system ciliopathy. If new evidence emerges of multi-system involvement in the ciliopathy spectrum then the rating can be reviewed.
Hereditary haemorrhagic telangiectasia v1.48 EPHB4 Louise Daugherty Phenotypes for gene: EPHB4 were changed from Capillary malformation-arteriovenous malformation 2; 618196; capillary malformation, epistaxis, telangiectasia, cerebral AVM to Capillary malformation-arteriovenous malformation 2; 618196; Capillary malformation, epistaxis, telangiectasia, cerebral AVM
Hereditary haemorrhagic telangiectasia v1.47 EPHB4 Louise Daugherty Added comment: Comment on phenotypes: Added phenotypes suggested from expert review that indicate relevance to inclusion on the Hereditary haemorrhagic telangiectasia panel
Hereditary haemorrhagic telangiectasia v1.47 EPHB4 Louise Daugherty Phenotypes for gene: EPHB4 were changed from Capillary malformation-arteriovenous malformation 2; 618196 to Capillary malformation-arteriovenous malformation 2; 618196; capillary malformation, epistaxis, telangiectasia, cerebral AVM
Hereditary haemorrhagic telangiectasia v1.46 EPHB4 Louise Daugherty Added comment: Comment on publications: Added PMID: 30760892 from external reviewer to support upgrading of gene to Green
Hereditary haemorrhagic telangiectasia v1.46 EPHB4 Louise Daugherty Publications for gene: EPHB4 were set to 28687708; 28730721
Hereditary haemorrhagic telangiectasia v1.45 EPHB4 Louise Daugherty Mode of inheritance for gene: EPHB4 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Cystic kidney disease v1.48 PKD1 Eleanor Williams Phenotypes for gene: PKD1 were changed from Polycystic kidney disease, adult type I, 173900 to Polycystic kidney disease, adult type I, 173900; Autosomal recessive polycystic kidney disease (ARPKD); Autosomal dominant polycystic kidney disease (ADPKD)
Cystic kidney disease v1.47 PKD1 Eleanor Williams Publications for gene: PKD1 were set to 19165178; 20558538; 22034641
Unexplained kidney failure in young people v1.68 PKD1 Eleanor Williams Phenotypes for gene: PKD1 were changed from Polycystic kidney disease, adult type I, 173900 to Polycystic kidney disease, adult type I, 173900; Autosomal recessive polycystic kidney disease (ARPKD); Autosomal dominant polycystic kidney disease (ADPKD)
Unexplained kidney failure in young people v1.67 PKD1 Eleanor Williams Publications for gene: PKD1 were set to 19165178; 20558538; 22034641
Unexplained kidney failure in young people v1.66 PKD1 Eleanor Williams Added comment: Comment on mode of inheritance: Updating the Mode of Inheritance to include the biallelic cases (PMIDs: * 20558538, 23624871)
Unexplained kidney failure in young people v1.66 PKD1 Eleanor Williams Mode of inheritance for gene: PKD1 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
Unexplained young onset end-stage renal disease v0.19 PKD1 Eleanor Williams Phenotypes for gene: PKD1 were changed from Polycystic kidney disease, adult type I, 173900 to Polycystic kidney disease, adult type I, 173900; Autosomal recessive polycystic kidney disease (ARPKD); Autosomal dominant polycystic kidney disease (ADPKD)
Unexplained young onset end-stage renal disease v0.18 PKD1 Eleanor Williams Publications for gene: PKD1 were set to 19165178; 22034641; 20558538
Fetal anomalies v0.287 PKD1 Eleanor Williams Added comment: Comment on mode of inheritance: updating MOI as biallelic cases have a more severe form of the disease
Fetal anomalies v0.287 PKD1 Eleanor Williams Mode of inheritance for gene: PKD1 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
Rare multisystem ciliopathy disorders v1.115 DCDC2 Rebecca Foulger Classified gene: DCDC2 as Red List (low evidence)
Rare multisystem ciliopathy disorders v1.115 DCDC2 Rebecca Foulger Added comment: Comment on list classification: Downgraded rating from Amber to Red following advice from Genomics England clinical team: Not a multi-system ciliopathy and therefore Red rating is appropriate. Note that DCDC2 is Green on the
Neonatal cholestasis panel, which is the appropriate panel for this gene.
Rare multisystem ciliopathy disorders v1.115 DCDC2 Rebecca Foulger Gene: dcdc2 has been classified as Red List (Low Evidence).
Rare multisystem ciliopathy disorders v1.114 IFT81 Rebecca Foulger commented on gene: IFT81: Amber rating agreed with Genomics England Clinical team: Gene is in the right pathway but 3/4 cases to date have one variant that is not able to be classified as pathogenic/likely pathogenic.
Severe insulin resistance and lipodystrophy syndromes v1.3 CAV1 Kevin Colclough edited their review of gene: CAV1: Added comment: 5 different loss of function variants have been reported in CAV1 to date associated with a lipodystrophy phenotype. No missense variants reported. GnomAD pLi score of 0.67 does not suggest that CAV1 is intolerant to loss of function variants.

Both heterozygous and homozygous LoF variants have been reported in patients with congenital lipodystrophy (PMID: 18211975, 25898808, 18237401).

A heterozygous c.-88del variant within the 5'UTR was identified in a patient with adult-onset partial lipodystrophy but with no proposed mechanism for a pathogenic effect on CAV1 (PMID: 18237401; the authors incorrectly described this a frameshift variant).

Frameshift variants within the C-terminal region of the gene that are predicted to escape NMD have been reported in patients with PAH but no lipodystrophy phenotype (PMID: 22474227).; Changed publications: PMID: 18390817, 18237401, 18211975, 25898808, 26176221, 22474227, 27717241, 11739396, 23049990; Changed phenotypes: ?Lipodystrophy, congenital generalized, type 3, 612526, Lipodystrophy, familial partial, type 7, 606721
Severe insulin resistance and lipodystrophy syndromes v1.3 CAV1 Kevin Colclough gene: CAV1 was added
gene: CAV1 was added to Lipodystrophy - childhood onset. Sources: Expert Review
Mode of inheritance for gene: CAV1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: CAV1 were set to PMID: 18390817; 18237401; 18211975; 25898808; 26176221; 27717241; 11739396; 23049990
Phenotypes for gene: CAV1 were set to ?Lipodystrophy, congenital generalized, type 3, 612526
Penetrance for gene: CAV1 were set to Complete
Review for gene: CAV1 was set to AMBER
gene: CAV1 was marked as current diagnostic
Added comment: Sources: Expert Review
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.123 RUNX2 Eleanor Williams changed review comment from: Loss of functional mutations associated with CLEIDOCRANIAL DYSPLASIA in Gene2Phenotype (confirmed).
In OMIM loss of function mutations are associated with several phenotypes including Cleidocranial dysplasia.
A heterozygous duplication of some exons of RUNX2 is associated with Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly . However, craniosynostosis is not listed as a feature of this disorder (PMID:  23290074, 25311905, 29891876

CNV EVIDENCE:

PMID: 20683987 - Mefford et al 2010 - Evaluated 186 individuals with single-suture craniosynostosis for submicroscopic deletions and duplications using whole-genome array CGH. They identified a heterozygous inverted 1.1 Mb duplication including the entire sequence of RUNX2, MIR586, and some of CLIC5 and SUPT3H in two affected cousins (1007 and 1019) with metopic synostosis and hypodontia. The duplication was inherited from the mother of one individual and it is presumed the father of the second individual (DNA not available, mother does not have the duplication). Both carrier parents have hypodontia by report, but neither is known to have had synostosis suggesting incomplete penetrance for that phenotype. The grandfather of 1007 and 1019 is described as having an abnormal head shape with a narrow forehead and several missing teeth; DNA was not available from this individual. They state that this CNV was not found in 2,493 control individuals [Itsara et al., 2009]. They compared RUNX2 expression levels in osteoblasts from these two individuals to expression levels in osteoblasts from unaffected individuals (n = 6) and individuals with synostosis but without duplication of RUNX2 (n = 22). The average expression of RUNX2 in the samples from the two individuals was higher than all affected and unaffected cell lines but it was not a statistically significant difference so should be interpreted with caution.

PMID: 23307468 - Varvagiannis et al 2013 - a girl with a de novo trisomy 6p12.3-p21.1 who showed craniosynostosis, manifested by the premature fusion of the right coronal and sagittal sutures, and also facial anomalies, psychomotor delay, and recurrent respiratory tract infections. MLPA analysis suggested a duplication of the entire RUNX2 gene. MLPA analysis indicated that the duplication was not present in parental blood samples. SNP array analysis identified the duplication was 6.9 Mb in size and mapped to 6p12.3–p21.1 (chr6: 40,797,975–47,701,961 NCBI Build 35; May 2004), thus encompassing 163 ENSEMBL genes. The finding of abnormal fontanelles and/or abnormal sutures, either manifested as craniosynostosis or not, has been documented in 5 cases in patients with pure partial trisomy 6p. No analysis of RUNX2 expression was performed.

PMID: 23348268 - Greives et al 2013 - present a case study of a boy with an atypical skull deformity with pan-craniosynostosis whose microarray analysis revealed 4 copies of a 1.24-Mb region from 6p12.3 to 6p21.1 containing the RUNX2 gene. He presented as an infant with airway obstruction from choanal atresia. He was diagnosed with a closed anterior fontanelle, ventricular septal defect, restricted range of motion in his elbows, mild conductive hearing loss, and developmental delays. They note that his multisutural craniosynostosis is the most extensive associated with RUNX2. No segregation analysis given.

PMID:25899668 - Molin et al 2015 - report on a family with an affected mother and three affected children. The four patients carried a 285 kb duplication identified by array comparative genomic hybridization. The duplication includes the entire sequence of RUNX2 and the 5' half of SUPT3H. We confirmed the duplication by real-time quantitative PCR in the four patients. Two children presented with the association of metopic craniosynostosis and oligo/hypodontia previously described, confirming the phenotype caused by RUNX2 duplication. The mother and one child had isolated hypodontia without craniosynostosis. The clinical presentation shown by syndromic patients IV‐1 and IV‐3 appears radically different from MDMHB, but shares a few similarities with previously duplication patients, including as hypodontia and craniosynostosis. Isolated hypodontia observed in Patients III‐2 and IV‐2 highlights a wider clinical spectrum associated with RUNX2 duplication, in addition to isolated and syndromic craniosynostosis and MDMHB.

Decipher - there are 6 patients with RUNX2 duplications over 1 kb in size. None mention craniosynostosis as a feature, although abnormality of the face/triangular face is listed for the patient with the 3.59 Mb duplication. https://decipher.sanger.ac.uk/gene/RUNX2#variants/RUNX2/patient-overlap/cnvs

Mouse models:

PMIDs: 11581292 (Liu et al 2001) and 12167715 (Geoffroy et al 2002) - both surprisingly report transgenic mice overexpressing Cbfa1 (runx2) developed severe osteopenia.

PMID: 21807129 - Maeno et al 2011 - report that in mice early onset of Runx2 expression in the cranial mesenchyme induced mineralization on E13.0, when no mineralization was observed in wild-type mice, and resulted in craniosynostosis.

PMID: 23300083 McGee-Lawrence et al 2013 - Runx2-deficient mice die at birth because of a lack of skeletal ossification. Axin2-deficient mice develop craniosynostosis because of high β-catenin activity. Runx2 represses transcription of Axin2 mRNA. They state that their data are consistent with the idea that Runx2 plays a central role in the etiologies of several different forms of craniosynostosis.

Control populations:
A search for the smallest CNV in a patient with craniosynostosis from Molin et al 2015 in the Database of Genomics Variants using GRCh38 coordinates shows no invidiuals from control populations with CNVs that cover RUNX2 http://dgv.tcag.ca/gb2/gbrowse/dgv2_hg38/?name=chr6%3A45265488-45551053;search=Search.

Summary:

Loss of function variants, partial duplication of the the RUNX2 gene and full duplication of the RUNX2 gene appear to result in different phenotypes. With regards to full duplication, there are 4 cases reported in separate publications of duplications fully covering the RUNX2 gene and patients with a craniosynostosis phenotype. The smallest duplication is 285 kb and includes RUNX2 and the 5' half of SUPT3H. However, there appears to be incomplete penetrance with some carriers having a less severe phenotype. Mefford et al state the CNV they report was not found in 2,493 control individuals and CNVs covering RUNX2 were not found in the Database of Genomics Variants. Mouse models give conflicting evidence. Mouse models of runx2 over-expression surprisingly found they developed severe osteopenia. However, early onset of Runx2 expression resulted in craniosynostosis, and Runx2 was found to repress Axin2, low levels of which can result in craniosynostosis. ; to: Loss of functional mutations associated with CLEIDOCRANIAL DYSPLASIA in Gene2Phenotype (confirmed).
In OMIM loss of function mutations are associated with several phenotypes including Cleidocranial dysplasia.
A heterozygous duplication of some exons of RUNX2 is associated with Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly . However, craniosynostosis is not listed as a feature of this disorder (PMID:  23290074, 25311905, 29891876

CNV EVIDENCE:

PMID: 20683987 - Mefford et al 2010 - Evaluated 186 individuals with single-suture craniosynostosis for submicroscopic deletions and duplications using whole-genome array CGH. They identified a heterozygous inverted 1.1 Mb duplication including the entire sequence of RUNX2, MIR586, and some of CLIC5 and SUPT3H in two affected cousins (1007 and 1019) with metopic synostosis and hypodontia. The duplication was inherited from the mother of one individual and it is presumed the father of the second individual (DNA not available, mother does not have the duplication). Both carrier parents have hypodontia by report, but neither is known to have had synostosis suggesting incomplete penetrance for that phenotype. The grandfather of 1007 and 1019 is described as having an abnormal head shape with a narrow forehead and several missing teeth; DNA was not available from this individual. They state that this CNV was not found in 2,493 control individuals [Itsara et al., 2009]. They compared RUNX2 expression levels in osteoblasts from these two individuals to expression levels in osteoblasts from unaffected individuals (n = 6) and individuals with synostosis but without duplication of RUNX2 (n = 22). The average expression of RUNX2 in the samples from the two individuals was higher than all affected and unaffected cell lines but it was not a statistically significant difference so should be interpreted with caution.

PMID: 23307468 - Varvagiannis et al 2013 - a girl with a de novo trisomy 6p12.3-p21.1 who showed craniosynostosis, manifested by the premature fusion of the right coronal and sagittal sutures, and also facial anomalies, psychomotor delay, and recurrent respiratory tract infections. MLPA analysis suggested a duplication of the entire RUNX2 gene. MLPA analysis indicated that the duplication was not present in parental blood samples. SNP array analysis identified the duplication was 6.9 Mb in size and mapped to 6p12.3–p21.1 (chr6: 40,797,975–47,701,961 NCBI Build 35; May 2004), thus encompassing 163 ENSEMBL genes. The finding of abnormal fontanelles and/or abnormal sutures, either manifested as craniosynostosis or not, has been documented in 5 cases in patients with pure partial trisomy 6p. No analysis of RUNX2 expression was performed.

PMID: 23348268 - Greives et al 2013 - present a case study of a boy with an atypical skull deformity with pan-craniosynostosis whose microarray analysis revealed 4 copies of a 1.24-Mb region from 6p12.3 to 6p21.1 containing the RUNX2 gene. He presented as an infant with airway obstruction from choanal atresia. He was diagnosed with a closed anterior fontanelle, ventricular septal defect, restricted range of motion in his elbows, mild conductive hearing loss, and developmental delays. They note that his multisutural craniosynostosis is the most extensive associated with RUNX2. No segregation analysis given.

PMID:25899668 - Molin et al 2015 - report on a family with an affected mother and three affected children. The four patients carried a 285 kb duplication identified by array comparative genomic hybridization. The duplication includes the entire sequence of RUNX2 and the 5' half of SUPT3H. We confirmed the duplication by real-time quantitative PCR in the four patients. Two children presented with the association of metopic craniosynostosis and oligo/hypodontia previously described, confirming the phenotype caused by RUNX2 duplication. The mother and one child had isolated hypodontia without craniosynostosis. The clinical presentation shown by syndromic patients IV‐1 and IV‐3 appears radically different from MDMHB, but shares a few similarities with previously duplication patients, including as hypodontia and craniosynostosis. Isolated hypodontia observed in Patients III‐2 and IV‐2 highlights a wider clinical spectrum associated with RUNX2 duplication, in addition to isolated and syndromic craniosynostosis and MDMHB.

Decipher - there are 6 patients with RUNX2 duplications over 1 kb in size. None mention craniosynostosis as a feature, although abnormality of the face/triangular face is listed for the patient with the 3.59 Mb duplication. https://decipher.sanger.ac.uk/gene/RUNX2#variants/RUNX2/patient-overlap/cnvs

Mouse models:

PMIDs: 11581292 (Liu et al 2001) and 12167715 (Geoffroy et al 2002) - both surprisingly report transgenic mice overexpressing Cbfa1 (runx2) developed severe osteopenia.

PMID: 21807129 - Maeno et al 2011 - report that in mice early onset of Runx2 expression in the cranial mesenchyme induced mineralization on E13.0, when no mineralization was observed in wild-type mice, and resulted in craniosynostosis.

PMID: 23300083 McGee-Lawrence et al 2013 - Runx2-deficient mice die at birth because of a lack of skeletal ossification. Axin2-deficient mice develop craniosynostosis because of high β-catenin activity. Runx2 represses transcription of Axin2 mRNA. They state that their data are consistent with the idea that Runx2 plays a central role in the etiologies of several different forms of craniosynostosis.

Control populations:
A search for the smallest CNV in a patient with craniosynostosis from Molin et al 2015 in the Database of Genomic Variants using GRCh38 coordinates shows no invidiuals from control populations with CNVs that cover RUNX2 http://dgv.tcag.ca/gb2/gbrowse/dgv2_hg38/?name=chr6%3A45265488-45551053;search=Search.

Summary:

Loss of function variants, partial duplication of the the RUNX2 gene and full duplication of the RUNX2 gene appear to result in different phenotypes. With regards to full duplication, there are 4 cases reported in separate publications of duplications fully covering the RUNX2 gene and patients with a craniosynostosis phenotype. The smallest duplication is 285 kb and includes RUNX2 and the 5' half of SUPT3H. However, there appears to be incomplete penetrance with some carriers having a less severe phenotype. Mefford et al state the CNV they report was not found in 2,493 control individuals and CNVs covering RUNX2 were not found in the Database of Genomics Variants. Mouse models give conflicting evidence. Mouse models of runx2 over-expression surprisingly found they developed severe osteopenia. However, early onset of Runx2 expression resulted in craniosynostosis, and Runx2 was found to repress Axin2, low levels of which can result in craniosynostosis.
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.123 RUNX2 Eleanor Williams changed review comment from: Loss of functional mutations associated with CLEIDOCRANIAL DYSPLASIA in Gene2Phenotype (confirmed).
In OMIM loss of function mutations are associated with several phenotypes including Cleidocranial dysplasia.
A heterozygous duplication of some exons of RUNX2 is associated with Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly . However, craniosynostosis is not listed as a feature of this disorder (PMID:  23290074, 25311905, 29891876

CNV EVIDENCE:

PMID: 20683987 - Mefford et al 2010 - Evaluated 186 individuals with single-suture craniosynostosis for submicroscopic deletions and duplications using whole-genome array CGH. They identified a heterozygous inverted 1.1 Mb duplication including the entire sequence of RUNX2, MIR586, and some of CLIC5 and SUPT3H in two affected cousins (1007 and 1019) with metopic synostosis and hypodontia. The duplication was inherited from the mother of one individual and it is presumed the father of the second individual (DNA not available, mother does not have the duplication). Both carrier parents have hypodontia by report, but neither is known to have had synostosis suggesting incomplete penetrance for that phenotype. The grandfather of 1007 and 1019 is described as having an abnormal head shape with a narrow forehead and several missing teeth; DNA was not available from this individual. They state that this CNV was not found in 2,493 control individuals [Itsara et al., 2009]. They compared RUNX2 expression levels in osteoblasts from these two individuals to expression levels in osteoblasts from unaffected individuals (n = 6) and individuals with synostosis but without duplication of RUNX2 (n = 22). The average expression of RUNX2 in the samples from the two individuals was higher than all affected and unaffected cell lines but it was not a statistically significant difference so should be interpreted with caution.

PMID: 23307468 - Varvagiannis et al 2013 - a girl with a de novo trisomy 6p12.3-p21.1 who showed craniosynostosis, manifested by the premature fusion of the right coronal and sagittal sutures, and also facial anomalies, psychomotor delay, and recurrent respiratory tract infections. MLPA analysis suggested a duplication of the entire RUNX2 gene. MLPA analysis indicated that the duplication was not present in parental blood samples. SNP array analysis identified the duplication was 6.9 Mb in size and mapped to 6p12.3–p21.1 (chr6: 40,797,975–47,701,961 NCBI Build 35; May 2004), thus encompassing 163 ENSEMBL genes. The finding of abnormal fontanelles and/or abnormal sutures, either manifested as craniosynostosis or not, has been documented in 5 cases in patients with pure partial trisomy 6p. No analysis of RUNX2 expression was performed.

PMID: 23348268 - Greives et al 2013 - present a case study of a boy with an atypical skull deformity with pan-craniosynostosis whose microarray analysis revealed 4 copies of a 1.24-Mb region from 6p12.3 to 6p21.1 containing the RUNX2 gene. He presented as an infant with airway obstruction from choanal atresia. He was diagnosed with a closed anterior fontanelle, ventricular septal defect, restricted range of motion in his elbows, mild conductive hearing loss, and developmental delays. They note that his multisutural craniosynostosis is the most extensive associated with RUNX2. No segregation analysis given.

PMID:25899668 - Molin et al 2015 - report on a family with an affected mother and three affected children. The four patients carried a 285 kb duplication identified by array comparative genomic hybridization. The duplication includes the entire sequence of RUNX2 and the 5' half of SUPT3H. We confirmed the duplication by real-time quantitative PCR in the four patients. Two children presented with the association of metopic craniosynostosis and oligo/hypodontia previously described, confirming the phenotype caused by RUNX2 duplication. The mother and one child had isolated hypodontia without craniosynostosis. The clinical presentation shown by syndromic patients IV‐1 and IV‐3 appears radically different from MDMHB, but shares a few similarities with previously duplication patients, including as hypodontia and craniosynostosis. Isolated hypodontia observed in Patients III‐2 and IV‐2 highlights a wider clinical spectrum associated with RUNX2 duplication, in addition to isolated and syndromic craniosynostosis and MDMHB.

Decipher - there are 6 patients with RUNX2 duplications over 1 kb in size. None mention craniosynostosis as a feature, although abnormality of the face/triangular face is listed for the patient with the 3.59 Mb duplication. https://decipher.sanger.ac.uk/gene/RUNX2#variants/RUNX2/patient-overlap/cnvs

Mouse models:

PMIDs: 11581292 (Liu et al 2001) and 12167715 (Geoffroy et al 2002) - both surprisingly report transgenic mice overexpressing Cbfa1 (runx2) developed severe osteopenia.

PMID: 21807129 - Maeno et al 2011 - report that in mice early onset of Runx2 expression in the cranial mesenchyme induced mineralization on E13.0, when no mineralization was observed in wild-type mice, and resulted in craniosynostosis.

PMID: 23300083 McGee-Lawrence et al 2013 - Runx2-deficient mice die at birth because of a lack of skeletal ossification. Axin2-deficient mice develop craniosynostosis because of high β-catenin activity. Runx2 represses transcription of Axin2 mRNA. They state that their data are consistent with the idea that Runx2 plays a central role in the etiologies of several different forms of craniosynostosis.

Summary:

Loss of function variants, partial duplication of the the RUNX2 gene and full duplication of the RUNX2 gene appear to result in different phenotypes. With regards to full duplication, there are 4 cases reported in separate publications of duplications fully covering the RUNX2 gene and patients with a craniosynostosis phenotype. The smallest duplication is 285 kb and includes RUNX2 and the 5' half of SUPT3H. However, there appears to be incomplete penetrance with some carriers having a less severe phenotype. Mefford et al state the CNV they report was not found in 2,493 control individuals. Mouse models give conflicting evidence. Mouse models of runx2 over-expression surprisingly found they developed severe osteopenia. However, early onset of Runx2 expression resulted in craniosynostosis, and Runx2 was found to repress Axin2, low levels of which can result in craniosynostosis. ; to: Loss of functional mutations associated with CLEIDOCRANIAL DYSPLASIA in Gene2Phenotype (confirmed).
In OMIM loss of function mutations are associated with several phenotypes including Cleidocranial dysplasia.
A heterozygous duplication of some exons of RUNX2 is associated with Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly . However, craniosynostosis is not listed as a feature of this disorder (PMID:  23290074, 25311905, 29891876

CNV EVIDENCE:

PMID: 20683987 - Mefford et al 2010 - Evaluated 186 individuals with single-suture craniosynostosis for submicroscopic deletions and duplications using whole-genome array CGH. They identified a heterozygous inverted 1.1 Mb duplication including the entire sequence of RUNX2, MIR586, and some of CLIC5 and SUPT3H in two affected cousins (1007 and 1019) with metopic synostosis and hypodontia. The duplication was inherited from the mother of one individual and it is presumed the father of the second individual (DNA not available, mother does not have the duplication). Both carrier parents have hypodontia by report, but neither is known to have had synostosis suggesting incomplete penetrance for that phenotype. The grandfather of 1007 and 1019 is described as having an abnormal head shape with a narrow forehead and several missing teeth; DNA was not available from this individual. They state that this CNV was not found in 2,493 control individuals [Itsara et al., 2009]. They compared RUNX2 expression levels in osteoblasts from these two individuals to expression levels in osteoblasts from unaffected individuals (n = 6) and individuals with synostosis but without duplication of RUNX2 (n = 22). The average expression of RUNX2 in the samples from the two individuals was higher than all affected and unaffected cell lines but it was not a statistically significant difference so should be interpreted with caution.

PMID: 23307468 - Varvagiannis et al 2013 - a girl with a de novo trisomy 6p12.3-p21.1 who showed craniosynostosis, manifested by the premature fusion of the right coronal and sagittal sutures, and also facial anomalies, psychomotor delay, and recurrent respiratory tract infections. MLPA analysis suggested a duplication of the entire RUNX2 gene. MLPA analysis indicated that the duplication was not present in parental blood samples. SNP array analysis identified the duplication was 6.9 Mb in size and mapped to 6p12.3–p21.1 (chr6: 40,797,975–47,701,961 NCBI Build 35; May 2004), thus encompassing 163 ENSEMBL genes. The finding of abnormal fontanelles and/or abnormal sutures, either manifested as craniosynostosis or not, has been documented in 5 cases in patients with pure partial trisomy 6p. No analysis of RUNX2 expression was performed.

PMID: 23348268 - Greives et al 2013 - present a case study of a boy with an atypical skull deformity with pan-craniosynostosis whose microarray analysis revealed 4 copies of a 1.24-Mb region from 6p12.3 to 6p21.1 containing the RUNX2 gene. He presented as an infant with airway obstruction from choanal atresia. He was diagnosed with a closed anterior fontanelle, ventricular septal defect, restricted range of motion in his elbows, mild conductive hearing loss, and developmental delays. They note that his multisutural craniosynostosis is the most extensive associated with RUNX2. No segregation analysis given.

PMID:25899668 - Molin et al 2015 - report on a family with an affected mother and three affected children. The four patients carried a 285 kb duplication identified by array comparative genomic hybridization. The duplication includes the entire sequence of RUNX2 and the 5' half of SUPT3H. We confirmed the duplication by real-time quantitative PCR in the four patients. Two children presented with the association of metopic craniosynostosis and oligo/hypodontia previously described, confirming the phenotype caused by RUNX2 duplication. The mother and one child had isolated hypodontia without craniosynostosis. The clinical presentation shown by syndromic patients IV‐1 and IV‐3 appears radically different from MDMHB, but shares a few similarities with previously duplication patients, including as hypodontia and craniosynostosis. Isolated hypodontia observed in Patients III‐2 and IV‐2 highlights a wider clinical spectrum associated with RUNX2 duplication, in addition to isolated and syndromic craniosynostosis and MDMHB.

Decipher - there are 6 patients with RUNX2 duplications over 1 kb in size. None mention craniosynostosis as a feature, although abnormality of the face/triangular face is listed for the patient with the 3.59 Mb duplication. https://decipher.sanger.ac.uk/gene/RUNX2#variants/RUNX2/patient-overlap/cnvs

Mouse models:

PMIDs: 11581292 (Liu et al 2001) and 12167715 (Geoffroy et al 2002) - both surprisingly report transgenic mice overexpressing Cbfa1 (runx2) developed severe osteopenia.

PMID: 21807129 - Maeno et al 2011 - report that in mice early onset of Runx2 expression in the cranial mesenchyme induced mineralization on E13.0, when no mineralization was observed in wild-type mice, and resulted in craniosynostosis.

PMID: 23300083 McGee-Lawrence et al 2013 - Runx2-deficient mice die at birth because of a lack of skeletal ossification. Axin2-deficient mice develop craniosynostosis because of high β-catenin activity. Runx2 represses transcription of Axin2 mRNA. They state that their data are consistent with the idea that Runx2 plays a central role in the etiologies of several different forms of craniosynostosis.

Control populations:
A search for the smallest CNV in a patient with craniosynostosis from Molin et al 2015 in the Database of Genomics Variants using GRCh38 coordinates shows no invidiuals from control populations with CNVs that cover RUNX2 http://dgv.tcag.ca/gb2/gbrowse/dgv2_hg38/?name=chr6%3A45265488-45551053;search=Search.

Summary:

Loss of function variants, partial duplication of the the RUNX2 gene and full duplication of the RUNX2 gene appear to result in different phenotypes. With regards to full duplication, there are 4 cases reported in separate publications of duplications fully covering the RUNX2 gene and patients with a craniosynostosis phenotype. The smallest duplication is 285 kb and includes RUNX2 and the 5' half of SUPT3H. However, there appears to be incomplete penetrance with some carriers having a less severe phenotype. Mefford et al state the CNV they report was not found in 2,493 control individuals and CNVs covering RUNX2 were not found in the Database of Genomics Variants. Mouse models give conflicting evidence. Mouse models of runx2 over-expression surprisingly found they developed severe osteopenia. However, early onset of Runx2 expression resulted in craniosynostosis, and Runx2 was found to repress Axin2, low levels of which can result in craniosynostosis.
Intellectual disability v2.890 ITPA Ivone Leong Phenotypes for gene: ITPA were changed from Epileptic encephalopathy, early infantile, 35 to Epileptic encephalopathy, early infantile, 35, 616647
Intellectual disability v2.889 ISCA2 Ivone Leong Publications for gene: ISCA2 were set to 25539947; 29297947; 29359243; 29122497; 28356563
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.123 RUNX2 Eleanor Williams changed review comment from: Loss of functional mutations associated with CLEIDOCRANIAL DYSPLASIA in Gene2Phenotype (confirmed).
In OMIM loss of function mutations are associated with several phenotypes including Cleidocranial dysplasia.
A heterozygous duplication of some exons of RUNX2 is associated with Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly . However, craniosynostosis is not listed as a feature of this disorder (PMID:  23290074, 25311905, 29891876

CNV EVIDENCE:

PMID: 20683987 - Mefford et al 2010 - Evaluated 186 individuals with single-suture craniosynostosis for submicroscopic deletions and duplications using whole-genome array CGH. They identified a heterozygous inverted 1.1 Mb duplication including the entire sequence of RUNX2, MIR586, and some of CLIC5 and SUPT3H in two affected cousins (1007 and 1019) with metopic synostosis and hypodontia. The duplication was inherited from the mother of one individual and it is presumed the father of the second individual (DNA not available, mother does not have the duplication). Both carrier parents have hypodontia by report, but neither is known to have had synostosis suggesting incomplete penetrance for that phenotype. The grandfather of 1007 and 1019 is described as having an abnormal head shape with a narrow forehead and several missing teeth; DNA was not available from this individual. They state that this CNV was not found in 2,493 control individuals [Itsara et al., 2009]. They compared RUNX2 expression levels in osteoblasts from these two individuals to expression levels in osteoblasts from unaffected individuals (n = 6) and individuals with synostosis but without duplication of RUNX2 (n = 22). The average expression of RUNX2 in the samples from the two individuals was higher than all affected and unaffected cell lines but it was not a statistically significant difference in RUNX2 expression levels so should be interpreted with caution.

PMID: 23307468 - Varvagiannis et al 2013 - a girl with a de novo trisomy 6p12.3-p21.1 who showed craniosynostosis, manifested by the premature fusion of the right coronal and sagittal sutures, and also facial anomalies, psychomotor delay, and recurrent respiratory tract infections. MLPA analysis suggested a duplication of the entire RUNX2 gene. MLPA analysis indicated that the duplication was not present in parental blood samples. SNP array analysis identified the duplication was 6.9 Mb in size and mapped to 6p12.3–p21.1 (chr6: 40,797,975–47,701,961 NCBI Build 35; May 2004), thus encompassing 163 ENSEMBL genes. The finding of abnormal fontanelles and/or abnormal sutures, either manifested as craniosynostosis or not, has been documented in 5 cases in patients with pure partial trisomy 6p. No analysis of RUNX2 expression was performed.

PMID: 23348268 - Greives et al 2013 - present a case study of a boy with an atypical skull deformity with pan-craniosynostosis whose microarray analysis revealed 4 copies of a 1.24-Mb region from 6p12.3 to 6p21.1 containing the RUNX2 gene. He presented as an infant with airway obstruction from choanal atresia. He was diagnosed with a closed anterior fontanelle, ventricular septal defect, restricted range of motion in his elbows, mild conductive hearing loss, and developmental delays. They note that his multisutural craniosynostosis is the most extensive associated with RUNX2. No segregation analysis given.

PMID:25899668 - Molin et al 2015 - report on a family with an affected mother and three affected children. The four patients carried a 285 kb duplication identified by array comparative genomic hybridization. The duplication includes the entire sequence of RUNX2 and the 5' half of SUPT3H. We confirmed the duplication by real-time quantitative PCR in the four patients. Two children presented with the association of metopic craniosynostosis and oligo/hypodontia previously described, confirming the phenotype caused by RUNX2 duplication. The mother and one child had isolated hypodontia without craniosynostosis. The clinical presentation shown by syndromic patients IV‐1 and IV‐3 appears radically different from MDMHB, but shares a few similarities with previously duplication patients, including as hypodontia and craniosynostosis. Isolated hypodontia observed in Patients III‐2 and IV‐2 highlights a wider clinical spectrum associated with RUNX2 duplication, in addition to isolated and syndromic craniosynostosis and MDMHB.

Decipher - there are 6 patients with RUNX2 duplications over 1 kb in size. None mention craniosynostosis as a feature, although abnormality of the face/triangular face is listed for the patient with the 3.59 Mb duplication. https://decipher.sanger.ac.uk/gene/RUNX2#variants/RUNX2/patient-overlap/cnvs

Mouse models:

PMIDs: 11581292 (Liu et al 2001) and 12167715 (Geoffroy et al 2002) - both surprisingly report transgenic mice overexpressing Cbfa1 (runx2) developed severe osteopenia.

PMID: 21807129 - Maeno et al 2011 - report that in mice early onset of Runx2 expression in the cranial mesenchyme induced mineralization on E13.0, when no mineralization was observed in wild-type mice, and resulted in craniosynostosis.

PMID: 23300083 McGee-Lawrence et al 2013 - Runx2-deficient mice die at birth because of a lack of skeletal ossification. Axin2-deficient mice develop craniosynostosis because of high β-catenin activity. Runx2 represses transcription of Axin2 mRNA. They state that their data are consistent with the idea that Runx2 plays a central role in the etiologies of several different forms of craniosynostosis.

Summary:

Loss of function variants, partial duplication of the the RUNX2 gene and full duplication of the RUNX2 gene appear to result in different phenotypes. With regards to full duplication, there are 4 cases reported in separate publications of duplications fully covering the RUNX2 gene and patients with a craniosynostosis phenotype. The smallest duplication is 285 kb and includes RUNX2 and the 5' half of SUPT3H. However, there appears to be incomplete penetrance with some carriers having a less severe phenotype. Mefford et al state the CNV they report was not found in 2,493 control individuals. Mouse models give conflicting evidence. Mouse models of runx2 over-expression surprisingly found they developed severe osteopenia. However, early onset of Runx2 expression resulted in craniosynostosis, and Runx2 was found to repress Axin2, low levels of which can result in craniosynostosis. ; to: Loss of functional mutations associated with CLEIDOCRANIAL DYSPLASIA in Gene2Phenotype (confirmed).
In OMIM loss of function mutations are associated with several phenotypes including Cleidocranial dysplasia.
A heterozygous duplication of some exons of RUNX2 is associated with Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly . However, craniosynostosis is not listed as a feature of this disorder (PMID:  23290074, 25311905, 29891876

CNV EVIDENCE:

PMID: 20683987 - Mefford et al 2010 - Evaluated 186 individuals with single-suture craniosynostosis for submicroscopic deletions and duplications using whole-genome array CGH. They identified a heterozygous inverted 1.1 Mb duplication including the entire sequence of RUNX2, MIR586, and some of CLIC5 and SUPT3H in two affected cousins (1007 and 1019) with metopic synostosis and hypodontia. The duplication was inherited from the mother of one individual and it is presumed the father of the second individual (DNA not available, mother does not have the duplication). Both carrier parents have hypodontia by report, but neither is known to have had synostosis suggesting incomplete penetrance for that phenotype. The grandfather of 1007 and 1019 is described as having an abnormal head shape with a narrow forehead and several missing teeth; DNA was not available from this individual. They state that this CNV was not found in 2,493 control individuals [Itsara et al., 2009]. They compared RUNX2 expression levels in osteoblasts from these two individuals to expression levels in osteoblasts from unaffected individuals (n = 6) and individuals with synostosis but without duplication of RUNX2 (n = 22). The average expression of RUNX2 in the samples from the two individuals was higher than all affected and unaffected cell lines but it was not a statistically significant difference so should be interpreted with caution.

PMID: 23307468 - Varvagiannis et al 2013 - a girl with a de novo trisomy 6p12.3-p21.1 who showed craniosynostosis, manifested by the premature fusion of the right coronal and sagittal sutures, and also facial anomalies, psychomotor delay, and recurrent respiratory tract infections. MLPA analysis suggested a duplication of the entire RUNX2 gene. MLPA analysis indicated that the duplication was not present in parental blood samples. SNP array analysis identified the duplication was 6.9 Mb in size and mapped to 6p12.3–p21.1 (chr6: 40,797,975–47,701,961 NCBI Build 35; May 2004), thus encompassing 163 ENSEMBL genes. The finding of abnormal fontanelles and/or abnormal sutures, either manifested as craniosynostosis or not, has been documented in 5 cases in patients with pure partial trisomy 6p. No analysis of RUNX2 expression was performed.

PMID: 23348268 - Greives et al 2013 - present a case study of a boy with an atypical skull deformity with pan-craniosynostosis whose microarray analysis revealed 4 copies of a 1.24-Mb region from 6p12.3 to 6p21.1 containing the RUNX2 gene. He presented as an infant with airway obstruction from choanal atresia. He was diagnosed with a closed anterior fontanelle, ventricular septal defect, restricted range of motion in his elbows, mild conductive hearing loss, and developmental delays. They note that his multisutural craniosynostosis is the most extensive associated with RUNX2. No segregation analysis given.

PMID:25899668 - Molin et al 2015 - report on a family with an affected mother and three affected children. The four patients carried a 285 kb duplication identified by array comparative genomic hybridization. The duplication includes the entire sequence of RUNX2 and the 5' half of SUPT3H. We confirmed the duplication by real-time quantitative PCR in the four patients. Two children presented with the association of metopic craniosynostosis and oligo/hypodontia previously described, confirming the phenotype caused by RUNX2 duplication. The mother and one child had isolated hypodontia without craniosynostosis. The clinical presentation shown by syndromic patients IV‐1 and IV‐3 appears radically different from MDMHB, but shares a few similarities with previously duplication patients, including as hypodontia and craniosynostosis. Isolated hypodontia observed in Patients III‐2 and IV‐2 highlights a wider clinical spectrum associated with RUNX2 duplication, in addition to isolated and syndromic craniosynostosis and MDMHB.

Decipher - there are 6 patients with RUNX2 duplications over 1 kb in size. None mention craniosynostosis as a feature, although abnormality of the face/triangular face is listed for the patient with the 3.59 Mb duplication. https://decipher.sanger.ac.uk/gene/RUNX2#variants/RUNX2/patient-overlap/cnvs

Mouse models:

PMIDs: 11581292 (Liu et al 2001) and 12167715 (Geoffroy et al 2002) - both surprisingly report transgenic mice overexpressing Cbfa1 (runx2) developed severe osteopenia.

PMID: 21807129 - Maeno et al 2011 - report that in mice early onset of Runx2 expression in the cranial mesenchyme induced mineralization on E13.0, when no mineralization was observed in wild-type mice, and resulted in craniosynostosis.

PMID: 23300083 McGee-Lawrence et al 2013 - Runx2-deficient mice die at birth because of a lack of skeletal ossification. Axin2-deficient mice develop craniosynostosis because of high β-catenin activity. Runx2 represses transcription of Axin2 mRNA. They state that their data are consistent with the idea that Runx2 plays a central role in the etiologies of several different forms of craniosynostosis.

Summary:

Loss of function variants, partial duplication of the the RUNX2 gene and full duplication of the RUNX2 gene appear to result in different phenotypes. With regards to full duplication, there are 4 cases reported in separate publications of duplications fully covering the RUNX2 gene and patients with a craniosynostosis phenotype. The smallest duplication is 285 kb and includes RUNX2 and the 5' half of SUPT3H. However, there appears to be incomplete penetrance with some carriers having a less severe phenotype. Mefford et al state the CNV they report was not found in 2,493 control individuals. Mouse models give conflicting evidence. Mouse models of runx2 over-expression surprisingly found they developed severe osteopenia. However, early onset of Runx2 expression resulted in craniosynostosis, and Runx2 was found to repress Axin2, low levels of which can result in craniosynostosis.
Intellectual disability v2.888 ISCA2 Ivone Leong Publications for gene: ISCA2 were set to 25539947, 29297947, 29359243
Intellectual disability v2.887 GEMIN4 Ivone Leong commented on gene: GEMIN4
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.123 RUNX2 Eleanor Williams changed review comment from: Loss of functional mutations associated with CLEIDOCRANIAL DYSPLASIA in Gene2Phenotype (confirmed).
In OMIM loss of function mutations are associated with several phenotypes including Cleidocranial dysplasia.
A heterozygous duplication of some exons of RUNX2 is associated with Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly . However, craniosynostosis is not listed as a feature of this disorder (PMID:  23290074, 25311905, 29891876

CNV EVIDENCE:

PMID: 20683987 - Mefford et al 2010 - Evaluated 186 individuals with single-suture craniosynostosis for submicroscopic deletions and duplications using whole-genome array CGH. They identified a heterozygous inverted 1.1 Mb duplication including the entire sequence of RUNX2, MIR586, and some of CLIC5 and SUPT3H in two affected cousins (1007 and 1019) with metopic synostosis and hypodontia. The duplication was inherited from the mother of one individual and it is presumed the father of the second individual (DNA not available, mother does not have the duplication). Both carrier parents have hypodontia by report, but neither is known to have had synostosis suggesting incomplete penetrance for that phenotype. The grandfather of 1007 and 1019 is described as having an abnormal head shape with a narrow forehead and several missing teeth; DNA was not available from this individual. They state that this CNV was not found in 2,493 control individuals [Itsara et al., 2009]. They compared RUNX2 expression levels in osteoblasts from these two individuals to expression levels in osteoblasts from unaffected individuals (n = 6) and individuals with synostosis but without duplication of RUNX2 (n = 22). The average expression of RUNX2 in the samples from the two individuals was higher than all affected and unaffected cell lines but it was not a statistically significant difference in RUNX2 expression levels so should be interpreted with caution.

PMID: 23307468 - Varvagiannis et al 2013 - a girl with a de novo trisomy 6p12.3-p21.1 who showed craniosynostosis, manifested by the premature fusion of the right coronal and sagittal sutures, and also facial anomalies, psychomotor delay, and recurrent respiratory tract infections. MLPA analysis suggested a duplication of the entire RUNX2 gene. MLPA analysis indicated that the duplication was not present in parental blood samples. SNP array analysis identified the duplication was 6.9 Mb in size and mapped to 6p12.3–p21.1 (chr6: 40,797,975–47,701,961 NCBI Build 35; May 2004), thus encompassing 163 ENSEMBL genes. The finding of abnormal fontanelles and/or abnormal sutures, either manifested as craniosynostosis or not, has been documented in 5 cases in patients with pure partial trisomy 6p. No analysis of RUNX2 expression was performed.

PMID: 23348268 - Greives et al 2013 - present a case study of a boy with an atypical skull deformity with pan-craniosynostosis whose microarray analysis revealed 4 copies of a 1.24-Mb region from 6p12.3 to 6p21.1 containing the RUNX2 gene. He presented as an infant with airway obstruction from choanal atresia. He was diagnosed with a closed anterior fontanelle, ventricular septal defect, restricted range of motion in his elbows, mild conductive hearing loss, and developmental delays. They note that his multisutural craniosynostosis is the most extensive associated with RUNX2. No segregation analysis given.

PMID:25899668 - Molin et al 2015 - report on a family with an affected mother and three affected children. The four patients carried a 285 kb duplication identified by array comparative genomic hybridization. The duplication includes the entire sequence of RUNX2 and the 5' half of SUPT3H. We confirmed the duplication by real-time quantitative PCR in the four patients. Two children presented with the association of metopic craniosynostosis and oligo/hypodontia previously described, confirming the phenotype caused by RUNX2 duplication. The mother and one child had isolated hypodontia without craniosynostosis. The clinical presentation shown by syndromic patients IV‐1 and IV‐3 appears radically different from MDMHB, but shares a few similarities with previously duplication patients, including as hypodontia and craniosynostosis. Isolated hypodontia observed in Patients III‐2 and IV‐2 highlights a wider clinical spectrum associated with RUNX2 duplication, in addition to isolated and syndromic craniosynostosis and MDMHB.

Decipher - there are 6 patients with RUNX2 duplications over 1 kb in size. None mention craniosynostosis as a feature, although abnormality of the face/triangular face is listed for the patient with the 3.59 Mb duplication. https://decipher.sanger.ac.uk/gene/RUNX2#variants/RUNX2/patient-overlap/cnvs

Mouse models:

PMIDs: 11581292 (Liu et al 2001) and 12167715 (Geoffroy et al 2002) - both surprisingly report transgenic mice overexpressing Cbfa1 (runx2) developed severe osteopenia.

PMID: 21807129 - Maeno et al 2011 - report that in mice early onset of Runx2 expression in the cranial mesenchyme induced mineralization on E13.0, when no mineralization was observed in wild-type mice, and resulted in craniosynostosis.

PMID: 23300083 McGee-Lawrence et al 2013 - Runx2-deficient mice die at birth because of a lack of skeletal ossification. Axin2-deficient mice develop craniosynostosis because of high β-catenin activity. Runx2 represses transcription of Axin2 mRNA. They state that their data are consistent with the idea that Runx2 plays a central role in the etiologies of several different forms of craniosynostosis.

Summary: Loss of function variants, partial duplication of the the RUNX2 gene and full duplication of the RUNX2 gene appear to result in different phenotypes. With regards to full duplication, there are 4 cases reported in separate publications of duplications fully covering the RUNX2 gene and patients with a craniosynostosis phenotype. The smallest duplication is 285 kb and includes RUNX2 and the 5' half of SUPT3H. However, there appears to be incomplete penetrance with some carriers having a less severe phenotype. Mefford et al state the CNV they report was not found in 2,493 control individuals. Mouse models give conflicting evidence. Mouse models of runx2 over-expression surprisingly found they developed severe osteopenia. However, early onset of Runx2 expression resulted in craniosynostosis, and Runx2 was found to repress Axin2, low levels of which can result in craniosynostosis. ; to: Loss of functional mutations associated with CLEIDOCRANIAL DYSPLASIA in Gene2Phenotype (confirmed).
In OMIM loss of function mutations are associated with several phenotypes including Cleidocranial dysplasia.
A heterozygous duplication of some exons of RUNX2 is associated with Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly . However, craniosynostosis is not listed as a feature of this disorder (PMID:  23290074, 25311905, 29891876

CNV EVIDENCE:

PMID: 20683987 - Mefford et al 2010 - Evaluated 186 individuals with single-suture craniosynostosis for submicroscopic deletions and duplications using whole-genome array CGH. They identified a heterozygous inverted 1.1 Mb duplication including the entire sequence of RUNX2, MIR586, and some of CLIC5 and SUPT3H in two affected cousins (1007 and 1019) with metopic synostosis and hypodontia. The duplication was inherited from the mother of one individual and it is presumed the father of the second individual (DNA not available, mother does not have the duplication). Both carrier parents have hypodontia by report, but neither is known to have had synostosis suggesting incomplete penetrance for that phenotype. The grandfather of 1007 and 1019 is described as having an abnormal head shape with a narrow forehead and several missing teeth; DNA was not available from this individual. They state that this CNV was not found in 2,493 control individuals [Itsara et al., 2009]. They compared RUNX2 expression levels in osteoblasts from these two individuals to expression levels in osteoblasts from unaffected individuals (n = 6) and individuals with synostosis but without duplication of RUNX2 (n = 22). The average expression of RUNX2 in the samples from the two individuals was higher than all affected and unaffected cell lines but it was not a statistically significant difference in RUNX2 expression levels so should be interpreted with caution.

PMID: 23307468 - Varvagiannis et al 2013 - a girl with a de novo trisomy 6p12.3-p21.1 who showed craniosynostosis, manifested by the premature fusion of the right coronal and sagittal sutures, and also facial anomalies, psychomotor delay, and recurrent respiratory tract infections. MLPA analysis suggested a duplication of the entire RUNX2 gene. MLPA analysis indicated that the duplication was not present in parental blood samples. SNP array analysis identified the duplication was 6.9 Mb in size and mapped to 6p12.3–p21.1 (chr6: 40,797,975–47,701,961 NCBI Build 35; May 2004), thus encompassing 163 ENSEMBL genes. The finding of abnormal fontanelles and/or abnormal sutures, either manifested as craniosynostosis or not, has been documented in 5 cases in patients with pure partial trisomy 6p. No analysis of RUNX2 expression was performed.

PMID: 23348268 - Greives et al 2013 - present a case study of a boy with an atypical skull deformity with pan-craniosynostosis whose microarray analysis revealed 4 copies of a 1.24-Mb region from 6p12.3 to 6p21.1 containing the RUNX2 gene. He presented as an infant with airway obstruction from choanal atresia. He was diagnosed with a closed anterior fontanelle, ventricular septal defect, restricted range of motion in his elbows, mild conductive hearing loss, and developmental delays. They note that his multisutural craniosynostosis is the most extensive associated with RUNX2. No segregation analysis given.

PMID:25899668 - Molin et al 2015 - report on a family with an affected mother and three affected children. The four patients carried a 285 kb duplication identified by array comparative genomic hybridization. The duplication includes the entire sequence of RUNX2 and the 5' half of SUPT3H. We confirmed the duplication by real-time quantitative PCR in the four patients. Two children presented with the association of metopic craniosynostosis and oligo/hypodontia previously described, confirming the phenotype caused by RUNX2 duplication. The mother and one child had isolated hypodontia without craniosynostosis. The clinical presentation shown by syndromic patients IV‐1 and IV‐3 appears radically different from MDMHB, but shares a few similarities with previously duplication patients, including as hypodontia and craniosynostosis. Isolated hypodontia observed in Patients III‐2 and IV‐2 highlights a wider clinical spectrum associated with RUNX2 duplication, in addition to isolated and syndromic craniosynostosis and MDMHB.

Decipher - there are 6 patients with RUNX2 duplications over 1 kb in size. None mention craniosynostosis as a feature, although abnormality of the face/triangular face is listed for the patient with the 3.59 Mb duplication. https://decipher.sanger.ac.uk/gene/RUNX2#variants/RUNX2/patient-overlap/cnvs

Mouse models:

PMIDs: 11581292 (Liu et al 2001) and 12167715 (Geoffroy et al 2002) - both surprisingly report transgenic mice overexpressing Cbfa1 (runx2) developed severe osteopenia.

PMID: 21807129 - Maeno et al 2011 - report that in mice early onset of Runx2 expression in the cranial mesenchyme induced mineralization on E13.0, when no mineralization was observed in wild-type mice, and resulted in craniosynostosis.

PMID: 23300083 McGee-Lawrence et al 2013 - Runx2-deficient mice die at birth because of a lack of skeletal ossification. Axin2-deficient mice develop craniosynostosis because of high β-catenin activity. Runx2 represses transcription of Axin2 mRNA. They state that their data are consistent with the idea that Runx2 plays a central role in the etiologies of several different forms of craniosynostosis.

Summary:

Loss of function variants, partial duplication of the the RUNX2 gene and full duplication of the RUNX2 gene appear to result in different phenotypes. With regards to full duplication, there are 4 cases reported in separate publications of duplications fully covering the RUNX2 gene and patients with a craniosynostosis phenotype. The smallest duplication is 285 kb and includes RUNX2 and the 5' half of SUPT3H. However, there appears to be incomplete penetrance with some carriers having a less severe phenotype. Mefford et al state the CNV they report was not found in 2,493 control individuals. Mouse models give conflicting evidence. Mouse models of runx2 over-expression surprisingly found they developed severe osteopenia. However, early onset of Runx2 expression resulted in craniosynostosis, and Runx2 was found to repress Axin2, low levels of which can result in craniosynostosis.
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.123 RUNX2 Eleanor Williams changed review comment from: Loss of functional mutations associated with CLEIDOCRANIAL DYSPLASIA in Gene2Phenotype (confirmed).
In OMIM loss of function mutations are associated with several phenotypes including Cleidocranial dysplasia.
A heterozygous duplication of some exons of RUNX2 is associated with Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly . However, craniosynostosis is not listed as a feature of this disorder (PMID:  23290074, 25311905, 29891876

CNV EVIDENCE:

PMID: 20683987 - Mefford et al 2010 - Evaluated 186 individuals with single-suture craniosynostosis for submicroscopic deletions and duplications using whole-genome array CGH. They identified a heterozygous inverted 1.1 Mb duplication including the entire sequence of RUNX2, MIR586, and some of CLIC5 and SUPT3H in two affected cousins (1007 and 1019) with metopic synostosis and hypodontia. The duplication was inherited from the mother of one individual and it is presumed the father of the second individual (DNA not available, mother does not have the duplication). Both carrier parents have hypodontia by report, but neither is known to have had synostosis suggesting incomplete penetrance for that phenotype. The grandfather of 1007 and 1019 is described as having an abnormal head shape with a narrow forehead and several missing teeth; DNA was not available from this individual. They compared RUNX2 expression levels in osteoblasts from these two individuals to expression levels in osteoblasts from unaffected individuals (n = 6) and individuals with synostosis but without duplication of RUNX2 (n = 22). The average expression of RUNX2 in the samples from the two individuals was higher than all affected and unaffected cell lines but it was not a statistically significant difference in RUNX2 expression levels so should be interpreted with caution.

PMID: 23307468 - Varvagiannis et al 2013 - a girl with a de novo trisomy 6p12.3-p21.1 who showed craniosynostosis, manifested by the premature fusion of the right coronal and sagittal sutures, and also facial anomalies, psychomotor delay, and recurrent respiratory tract infections. MLPA analysis suggested a duplication of the entire RUNX2 gene. MLPA analysis indicated that the duplication was not present in parental blood samples. SNP array analysis identified the duplication was 6.9 Mb in size and mapped to 6p12.3–p21.1 (chr6: 40,797,975–47,701,961 NCBI Build 35; May 2004), thus encompassing 163 ENSEMBL genes. The finding of abnormal fontanelles and/or abnormal sutures, either manifested as craniosynostosis or not, has been documented in 5 cases in patients with pure partial trisomy 6p. No analysis of RUNX2 expression was performed.

PMID: 23348268 - Greives et al 2013 - present a case study of a boy with an atypical skull deformity with pan-craniosynostosis whose microarray analysis revealed 4 copies of a 1.24-Mb region from 6p12.3 to 6p21.1 containing the RUNX2 gene. He presented as an infant with airway obstruction from choanal atresia. He was diagnosed with a closed anterior fontanelle, ventricular septal defect, restricted range of motion in his elbows, mild conductive hearing loss, and developmental delays. No segregation analysis given.

PMID: McGee-Lawrence et al 2013 - Axin2-deficient mice develop craniosynostosis because of high β-catenin activity. Runx2 represses transcription of Axin2 mRNA. To determine whether Runx2 contributes to the etiology of Axin2 deficiency-induced craniosynostosis, they generated Axin2(-/-):Runx2(+/-) mice. These double mutant mice had longer skulls than Axin2(-/-) mice, indicating that Runx2 haploinsufficiency rescued the craniosynostosis phenotype of Axin2(-/-) mice

PMID:25899668 - Molin et al 2015 - report on a family with an affected mother and three affected children. The four patients carried a 285 kb duplication identified by array comparative genomic hybridization. The duplication includes the entire sequence of RUNX2 and the 5' half of SUPT3H. We confirmed the duplication by real-time quantitative PCR in the four patients. Two children presented with the association of metopic craniosynostosis and oligo/hypodontia previously described, confirming the phenotype caused by RUNX2 duplication. The mother and one child had isolated hypodontia without craniosynostosis. The clinical presentation shown by syndromic Patients IV‐1 and IV‐3 appears radically different from MDMHB, but shares a few similarities with previously duplication patients, including as hypodontia and craniosynostosis. Isolated hypodontia observed in Patients III‐2 and IV‐2 highlights a wider clinical spectrum associated with RUNX2 duplication, in addition to isolated and syndromic craniosynostosis and MDMHB.

Decipher - there are 6 patients with RUNX2 duplications over 1 kb in size. None mention craniosynostosis as a feature, although abnormality of the face/triangular face is listed for the patient with the 3.59 Mb duplication. https://decipher.sanger.ac.uk/gene/RUNX2#variants/RUNX2/patient-overlap/cnvs

Summary: Loss of function variants, partial duplication of the the RUNX2 gene and full duplication of the RUNX2 gene appear to result in different phenotypes. With regards to full duplication, there are 4 cases reported in separate publications of duplications fully covering the RUNX2 gene and patients with a craniosynostosis phenotype. The smallest duplication is 285 kb and includes RUNX2 and the 5' half of SUPT3H. However, there appears to be incomplete penetrance with some carriers having a less severe phenotype. Frequency of CNVs covering this region in the general population have not been reported.; to: Loss of functional mutations associated with CLEIDOCRANIAL DYSPLASIA in Gene2Phenotype (confirmed).
In OMIM loss of function mutations are associated with several phenotypes including Cleidocranial dysplasia.
A heterozygous duplication of some exons of RUNX2 is associated with Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly . However, craniosynostosis is not listed as a feature of this disorder (PMID:  23290074, 25311905, 29891876

CNV EVIDENCE:

PMID: 20683987 - Mefford et al 2010 - Evaluated 186 individuals with single-suture craniosynostosis for submicroscopic deletions and duplications using whole-genome array CGH. They identified a heterozygous inverted 1.1 Mb duplication including the entire sequence of RUNX2, MIR586, and some of CLIC5 and SUPT3H in two affected cousins (1007 and 1019) with metopic synostosis and hypodontia. The duplication was inherited from the mother of one individual and it is presumed the father of the second individual (DNA not available, mother does not have the duplication). Both carrier parents have hypodontia by report, but neither is known to have had synostosis suggesting incomplete penetrance for that phenotype. The grandfather of 1007 and 1019 is described as having an abnormal head shape with a narrow forehead and several missing teeth; DNA was not available from this individual. They state that this CNV was not found in 2,493 control individuals [Itsara et al., 2009]. They compared RUNX2 expression levels in osteoblasts from these two individuals to expression levels in osteoblasts from unaffected individuals (n = 6) and individuals with synostosis but without duplication of RUNX2 (n = 22). The average expression of RUNX2 in the samples from the two individuals was higher than all affected and unaffected cell lines but it was not a statistically significant difference in RUNX2 expression levels so should be interpreted with caution.

PMID: 23307468 - Varvagiannis et al 2013 - a girl with a de novo trisomy 6p12.3-p21.1 who showed craniosynostosis, manifested by the premature fusion of the right coronal and sagittal sutures, and also facial anomalies, psychomotor delay, and recurrent respiratory tract infections. MLPA analysis suggested a duplication of the entire RUNX2 gene. MLPA analysis indicated that the duplication was not present in parental blood samples. SNP array analysis identified the duplication was 6.9 Mb in size and mapped to 6p12.3–p21.1 (chr6: 40,797,975–47,701,961 NCBI Build 35; May 2004), thus encompassing 163 ENSEMBL genes. The finding of abnormal fontanelles and/or abnormal sutures, either manifested as craniosynostosis or not, has been documented in 5 cases in patients with pure partial trisomy 6p. No analysis of RUNX2 expression was performed.

PMID: 23348268 - Greives et al 2013 - present a case study of a boy with an atypical skull deformity with pan-craniosynostosis whose microarray analysis revealed 4 copies of a 1.24-Mb region from 6p12.3 to 6p21.1 containing the RUNX2 gene. He presented as an infant with airway obstruction from choanal atresia. He was diagnosed with a closed anterior fontanelle, ventricular septal defect, restricted range of motion in his elbows, mild conductive hearing loss, and developmental delays. They note that his multisutural craniosynostosis is the most extensive associated with RUNX2. No segregation analysis given.

PMID:25899668 - Molin et al 2015 - report on a family with an affected mother and three affected children. The four patients carried a 285 kb duplication identified by array comparative genomic hybridization. The duplication includes the entire sequence of RUNX2 and the 5' half of SUPT3H. We confirmed the duplication by real-time quantitative PCR in the four patients. Two children presented with the association of metopic craniosynostosis and oligo/hypodontia previously described, confirming the phenotype caused by RUNX2 duplication. The mother and one child had isolated hypodontia without craniosynostosis. The clinical presentation shown by syndromic patients IV‐1 and IV‐3 appears radically different from MDMHB, but shares a few similarities with previously duplication patients, including as hypodontia and craniosynostosis. Isolated hypodontia observed in Patients III‐2 and IV‐2 highlights a wider clinical spectrum associated with RUNX2 duplication, in addition to isolated and syndromic craniosynostosis and MDMHB.

Decipher - there are 6 patients with RUNX2 duplications over 1 kb in size. None mention craniosynostosis as a feature, although abnormality of the face/triangular face is listed for the patient with the 3.59 Mb duplication. https://decipher.sanger.ac.uk/gene/RUNX2#variants/RUNX2/patient-overlap/cnvs

Mouse models:

PMIDs: 11581292 (Liu et al 2001) and 12167715 (Geoffroy et al 2002) - both surprisingly report transgenic mice overexpressing Cbfa1 (runx2) developed severe osteopenia.

PMID: 21807129 - Maeno et al 2011 - report that in mice early onset of Runx2 expression in the cranial mesenchyme induced mineralization on E13.0, when no mineralization was observed in wild-type mice, and resulted in craniosynostosis.

PMID: 23300083 McGee-Lawrence et al 2013 - Runx2-deficient mice die at birth because of a lack of skeletal ossification. Axin2-deficient mice develop craniosynostosis because of high β-catenin activity. Runx2 represses transcription of Axin2 mRNA. They state that their data are consistent with the idea that Runx2 plays a central role in the etiologies of several different forms of craniosynostosis.

Summary: Loss of function variants, partial duplication of the the RUNX2 gene and full duplication of the RUNX2 gene appear to result in different phenotypes. With regards to full duplication, there are 4 cases reported in separate publications of duplications fully covering the RUNX2 gene and patients with a craniosynostosis phenotype. The smallest duplication is 285 kb and includes RUNX2 and the 5' half of SUPT3H. However, there appears to be incomplete penetrance with some carriers having a less severe phenotype. Mefford et al state the CNV they report was not found in 2,493 control individuals. Mouse models give conflicting evidence. Mouse models of runx2 over-expression surprisingly found they developed severe osteopenia. However, early onset of Runx2 expression resulted in craniosynostosis, and Runx2 was found to repress Axin2, low levels of which can result in craniosynostosis.
Intellectual disability v2.887 ISCA2 Ivone Leong Phenotypes for gene: ISCA2 were changed from Multiple mitochondrial dysfunctions syndrome 4 to Multiple mitochondrial dysfunctions syndrome 4, 616370
Intellectual disability v2.886 GEMIN4 Ivone Leong Phenotypes for gene: GEMIN4 were changed from Neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities to Neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities, 617913
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.123 RUNX2 Eleanor Williams commented on gene: RUNX2: Loss of functional mutations associated with CLEIDOCRANIAL DYSPLASIA in Gene2Phenotype (confirmed).
In OMIM loss of function mutations are associated with several phenotypes including Cleidocranial dysplasia.
A heterozygous duplication of some exons of RUNX2 is associated with Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly . However, craniosynostosis is not listed as a feature of this disorder (PMID:  23290074, 25311905, 29891876

CNV EVIDENCE:

PMID: 20683987 - Mefford et al 2010 - Evaluated 186 individuals with single-suture craniosynostosis for submicroscopic deletions and duplications using whole-genome array CGH. They identified a heterozygous inverted 1.1 Mb duplication including the entire sequence of RUNX2, MIR586, and some of CLIC5 and SUPT3H in two affected cousins (1007 and 1019) with metopic synostosis and hypodontia. The duplication was inherited from the mother of one individual and it is presumed the father of the second individual (DNA not available, mother does not have the duplication). Both carrier parents have hypodontia by report, but neither is known to have had synostosis suggesting incomplete penetrance for that phenotype. The grandfather of 1007 and 1019 is described as having an abnormal head shape with a narrow forehead and several missing teeth; DNA was not available from this individual. They compared RUNX2 expression levels in osteoblasts from these two individuals to expression levels in osteoblasts from unaffected individuals (n = 6) and individuals with synostosis but without duplication of RUNX2 (n = 22). The average expression of RUNX2 in the samples from the two individuals was higher than all affected and unaffected cell lines but it was not a statistically significant difference in RUNX2 expression levels so should be interpreted with caution.

PMID: 23307468 - Varvagiannis et al 2013 - a girl with a de novo trisomy 6p12.3-p21.1 who showed craniosynostosis, manifested by the premature fusion of the right coronal and sagittal sutures, and also facial anomalies, psychomotor delay, and recurrent respiratory tract infections. MLPA analysis suggested a duplication of the entire RUNX2 gene. MLPA analysis indicated that the duplication was not present in parental blood samples. SNP array analysis identified the duplication was 6.9 Mb in size and mapped to 6p12.3–p21.1 (chr6: 40,797,975–47,701,961 NCBI Build 35; May 2004), thus encompassing 163 ENSEMBL genes. The finding of abnormal fontanelles and/or abnormal sutures, either manifested as craniosynostosis or not, has been documented in 5 cases in patients with pure partial trisomy 6p. No analysis of RUNX2 expression was performed.

PMID: 23348268 - Greives et al 2013 - present a case study of a boy with an atypical skull deformity with pan-craniosynostosis whose microarray analysis revealed 4 copies of a 1.24-Mb region from 6p12.3 to 6p21.1 containing the RUNX2 gene. He presented as an infant with airway obstruction from choanal atresia. He was diagnosed with a closed anterior fontanelle, ventricular septal defect, restricted range of motion in his elbows, mild conductive hearing loss, and developmental delays. No segregation analysis given.

PMID: McGee-Lawrence et al 2013 - Axin2-deficient mice develop craniosynostosis because of high β-catenin activity. Runx2 represses transcription of Axin2 mRNA. To determine whether Runx2 contributes to the etiology of Axin2 deficiency-induced craniosynostosis, they generated Axin2(-/-):Runx2(+/-) mice. These double mutant mice had longer skulls than Axin2(-/-) mice, indicating that Runx2 haploinsufficiency rescued the craniosynostosis phenotype of Axin2(-/-) mice

PMID:25899668 - Molin et al 2015 - report on a family with an affected mother and three affected children. The four patients carried a 285 kb duplication identified by array comparative genomic hybridization. The duplication includes the entire sequence of RUNX2 and the 5' half of SUPT3H. We confirmed the duplication by real-time quantitative PCR in the four patients. Two children presented with the association of metopic craniosynostosis and oligo/hypodontia previously described, confirming the phenotype caused by RUNX2 duplication. The mother and one child had isolated hypodontia without craniosynostosis. The clinical presentation shown by syndromic Patients IV‐1 and IV‐3 appears radically different from MDMHB, but shares a few similarities with previously duplication patients, including as hypodontia and craniosynostosis. Isolated hypodontia observed in Patients III‐2 and IV‐2 highlights a wider clinical spectrum associated with RUNX2 duplication, in addition to isolated and syndromic craniosynostosis and MDMHB.

Decipher - there are 6 patients with RUNX2 duplications over 1 kb in size. None mention craniosynostosis as a feature, although abnormality of the face/triangular face is listed for the patient with the 3.59 Mb duplication. https://decipher.sanger.ac.uk/gene/RUNX2#variants/RUNX2/patient-overlap/cnvs

Summary: Loss of function variants, partial duplication of the the RUNX2 gene and full duplication of the RUNX2 gene appear to result in different phenotypes. With regards to full duplication, there are 4 cases reported in separate publications of duplications fully covering the RUNX2 gene and patients with a craniosynostosis phenotype. The smallest duplication is 285 kb and includes RUNX2 and the 5' half of SUPT3H. However, there appears to be incomplete penetrance with some carriers having a less severe phenotype. Frequency of CNVs covering this region in the general population have not been reported.
Intellectual disability v2.885 CWC27 Ivone Leong Phenotypes for gene: CWC27 were changed from Retinitis pigmentosa with or without skeletal anomalies to Retinitis pigmentosa with or without skeletal anomalies, 250410
Familial non syndromic congenital heart disease v1.46 ABL1 Rebecca Foulger changed review comment from: Comment on list classification: Updated rating from Amber to Red based on advice from Helen Brittain. Wang et al. 2017 (PMID:28288113) report ABL1 germline variants (2 variants, 4 families) cosegregating with an autosomal dominant disorder characterized by congenital heart disease, skeletal abnormalities and failure to thrive. ABL1 is on this heart panel based on ventral/atrial septal defects (VSD/ASD) seen in individuals from all four families in PMID:28288113.; to: Comment on list classification: Updated rating from Amber to Green based on advice from Helen Brittain. Wang et al. 2017 (PMID:28288113) report ABL1 germline variants (2 variants, 4 families) cosegregating with an autosomal dominant disorder characterized by congenital heart disease, skeletal abnormalities and failure to thrive. ABL1 is on this heart panel based on ventral/atrial septal defects (VSD/ASD) seen in individuals from all four families in PMID:28288113.
Childhood solid tumours v1.25 WRN Ivone Leong Source Expert list was added to WRN.
Source Expert Review Green was added to WRN.
Mode of inheritance for gene WRN was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Werner syndrome, 277700 for gene: WRN
Rating Changed from Red List (low evidence) to Green List (high evidence)
Childhood solid tumours v1.25 VHL Ivone Leong Source Expert list was added to VHL.
Source Expert Review Green was added to VHL.
Mode of inheritance for gene VHL was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added phenotypes von Hippel-Lindau syndrome, 193300 for gene: VHL
Rating Changed from Red List (low evidence) to Green List (high evidence)
Childhood solid tumours v1.25 SUFU Ivone Leong Source Expert list was added to SUFU.
Source Expert Review Green was added to SUFU.
Mode of inheritance for gene SUFU was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added phenotypes Medulloblastoma, desmoplastic, 155255; Basal cell nevus syndrome, 109400 for gene: SUFU
Publications for gene SUFU were changed from to 19533801; 29186568; 22829011; 25403219
Rating Changed from Red List (low evidence) to Green List (high evidence)
Childhood solid tumours v1.25 STK11 Ivone Leong Source Expert list was added to STK11.
Source Expert Review Green was added to STK11.
Mode of inheritance for gene STK11 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added phenotypes Peutz-Jeghers syndrome, 175200 for gene: STK11
Rating Changed from Red List (low evidence) to Green List (high evidence)
Childhood solid tumours v1.25 SMAD4 Ivone Leong Source Expert list was added to SMAD4.
Source Expert Review Green was added to SMAD4.
Mode of inheritance for gene SMAD4 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added phenotypes Polyposis, juvenile intestinal, 174900 for gene: SMAD4
Rating Changed from Red List (low evidence) to Green List (high evidence)
Childhood solid tumours v1.25 PDGFRA Ivone Leong Source Expert list was added to PDGFRA.
Source Expert Review Green was added to PDGFRA.
Mode of inheritance for gene PDGFRA was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added phenotypes Familial Gastrointestinal stromal tumour; Gastrointestinal stromal tumor, somatic, 606764 for gene: PDGFRA
Publications for gene PDGFRA were changed from to 17566086; 14699510; 25975287; 17087943
Rating Changed from Red List (low evidence) to Green List (high evidence)
Childhood solid tumours v1.25 MEN1 Ivone Leong Source Expert list was added to MEN1.
Source Expert Review Green was added to MEN1.
Mode of inheritance for gene MEN1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added phenotypes Multiple endocrine neoplasia 1, 131100 for gene: MEN1
Rating Changed from Red List (low evidence) to Green List (high evidence)
Childhood solid tumours v1.25 BMPR1A Ivone Leong Source Expert list was added to BMPR1A.
Source Expert Review Green was added to BMPR1A.
Mode of inheritance for gene BMPR1A was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added phenotypes Hereditary Mixed Polyposis Syndrome 2, 610069; Polyposis, juvenile intestinal, 174900 for gene: BMPR1A
Publications for gene BMPR1A were changed from to 23539595; 12136244; 11536076; 11381269
Rating Changed from Red List (low evidence) to Green List (high evidence)
Childhood solid tumours v1.24 SUFU Ivone Leong reviewed gene: SUFU: Rating: GREEN; Mode of pathogenicity: None; Publications: 19533801, 22829011, 25403219, 29186568; Phenotypes: ; Mode of inheritance: None
Familial non syndromic congenital heart disease v1.46 TAB2 Sarah Leigh changed review comment from: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 4 nonsense variants reported in unrelated cases.; to: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 4 nonsense variants reported in unrelated cases.
Watch list tag has been removed as sufficient variants have now been reported.
Familial non syndromic congenital heart disease v1.46 TAB2 Sarah Leigh Classified gene: TAB2 as Green List (high evidence)
Familial non syndromic congenital heart disease v1.46 TAB2 Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 4 nonsense variants reported in unrelated cases.
Familial non syndromic congenital heart disease v1.46 TAB2 Sarah Leigh Gene: tab2 has been classified as Green List (High Evidence).
Familial non syndromic congenital heart disease v1.45 TAB2 Sarah Leigh Tag watchlist was removed from gene: TAB2.
Childhood solid tumours v1.24 PDGFRA Ivone Leong reviewed gene: PDGFRA: Rating: GREEN; Mode of pathogenicity: None; Publications: 17087943, 14699510, 25975287, 17566086; Phenotypes: ; Mode of inheritance: None
Childhood solid tumours v1.24 BMPR1A Ivone Leong reviewed gene: BMPR1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 11381269, 12136244, 11536076; Phenotypes: ; Mode of inheritance: None
Intellectual disability v2.884 CUX2 Sarah Leigh Classified gene: CUX2 as Green List (high evidence)
Intellectual disability v2.884 CUX2 Sarah Leigh Added comment: Comment on list classification: Following personal comunication with Gemma Louise Carvill, the variant was confirmed as de novo in all nine cases mentioned in PMID 29630738.
Intellectual disability v2.884 CUX2 Sarah Leigh Gene: cux2 has been classified as Green List (High Evidence).
Proteinuric renal disease v1.212 XPO5 Eleanor Williams Phenotypes for gene: XPO5 were changed from to Nephrotic syndrome
Proteinuric renal disease v1.211 XPO5 Eleanor Williams Publications for gene: XPO5 were set to
Proteinuric renal disease v1.210 SLC19A3 Eleanor Williams Phenotypes for gene: SLC19A3 were changed from Thiamine metabolism dysfunction syndrome 2 (biotin- or thiamine-responsive; (originally on the Imerslund-Grasbeck syndrome gene panel) to Thiamine metabolism dysfunction syndrome 2 (biotin- or thiamine-responsive encephalopathy type 2) #607483; (originally on the Imerslund-Grasbeck syndrome gene panel)
Proteinuric renal disease v1.209 NXF5 Eleanor Williams Phenotypes for gene: NXF5 were changed from to FSGS; heart-block disorder
Proteinuric renal disease v1.208 NXF5 Eleanor Williams Publications for gene: NXF5 were set to
Proteinuric renal disease v1.207 NLRP3 Eleanor Williams Phenotypes for gene: NLRP3 were changed from to SRNS
Proteinuric renal disease v1.206 NLRP3 Eleanor Williams Publications for gene: NLRP3 were set to
Proteinuric renal disease v1.205 NEU1 Eleanor Williams Phenotypes for gene: NEU1 were changed from to SRNS
Proteinuric renal disease v1.204 NEU1 Eleanor Williams Publications for gene: NEU1 were set to
Proteinuric renal disease v1.203 NEIL1 Eleanor Williams Phenotypes for gene: NEIL1 were changed from to SRNS
Proteinuric renal disease v1.202 NEIL1 Eleanor Williams Publications for gene: NEIL1 were set to
Proteinuric renal disease v1.201 LAMA5 Eleanor Williams Publications for gene: LAMA5 were set to
Proteinuric renal disease v1.200 KANK4 Eleanor Williams Publications for gene: KANK4 were set to
Proteinuric renal disease v1.199 KANK1 Eleanor Williams Phenotypes for gene: KANK1 were changed from to Steroid sensitive resistant nephrotic syndrome
Proteinuric renal disease v1.198 KANK1 Eleanor Williams Publications for gene: KANK1 were set to
Proteinuric renal disease v1.197 E2F3 Eleanor Williams Phenotypes for gene: E2F3 were changed from to FSGS; mental retardation
Proteinuric renal disease v1.196 E2F3 Eleanor Williams Publications for gene: E2F3 were set to
Proteinuric renal disease v1.195 CYP11B2 Eleanor Williams Phenotypes for gene: CYP11B2 were changed from to Hypoaldosteronism, congenital, due to CMO I deficiency #203400; Hypoaldosteronism, congenital, due to CMO II deficiency #610600
Proteinuric renal disease v1.194 CYP11B2 Eleanor Williams Publications for gene: CYP11B2 were set to
Proteinuric renal disease v1.193 COQ9 Eleanor Williams Phenotypes for gene: COQ9 were changed from to Coenzyme Q10 deficiency, primary, 5 #614654
Proteinuric renal disease v1.192 COQ9 Eleanor Williams Publications for gene: COQ9 were set to
Proteinuric renal disease v1.191 COQ7 Eleanor Williams Phenotypes for gene: COQ7 were changed from to ?Coenzyme Q10 deficiency, primary, 8 #616733
Proteinuric renal disease v1.190 COQ7 Eleanor Williams Publications for gene: COQ7 were set to
Intellectual disability v2.883 CHKB Ivone Leong Classified gene: CHKB as Green List (high evidence)
Intellectual disability v2.883 CHKB Ivone Leong Added comment: Comment on list classification: Promoted from red to green based on expert review. CHKB is associated with a phenotype in OMIM but not in Gene2Phenotype. There are >10 unrelated cases with different variants reported in the literature of patients with congenital muscular dystrophy who also have intellectual disability.
Intellectual disability v2.883 CHKB Ivone Leong Gene: chkb has been classified as Green List (High Evidence).
Intellectual disability v2.882 CHKB Ivone Leong Publications for gene: CHKB were set to 21665002
Mitochondrial disorders v1.400 MTPAP Sarah Leigh Publications for gene: MTPAP were set to 20970105; 25008111; 26319014
Mitochondrial disorders v1.399 IARS2 Sarah Leigh Classified gene: IARS2 as Amber List (moderate evidence)
Mitochondrial disorders v1.399 IARS2 Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as possible Gen2Phen gene. At least 2 variants reported, together with supportive functional studies.
Mitochondrial disorders v1.399 IARS2 Sarah Leigh Gene: iars2 has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v1.398 IARS2 Sarah Leigh Added comment: Comment on phenotypes: ?Cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia 616007, also known as CAGSSS
Mitochondrial disorders v1.398 IARS2 Sarah Leigh Phenotypes for gene: IARS2 were changed from No OMIM phenotype; CAGSSS - Cataracts (CA), growth hormone deficiency (G), sensory neuropathy (S), sensorineural hearing loss (S), and skeletal dysplasia (S) to ?Cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia 616007
Possible mitochondrial disorder, nuclear genes v0.202 IARS2 Sarah Leigh Publications for gene: IARS2 were set to
Mitochondrial disorders v1.397 IARS2 Sarah Leigh changed review comment from: Comment on publications: PMID: 25130867 (3 related cases with CAGSSS homozygous for a rare nonsynonymous variant in this gene, an unrelated case with Leigh syndrome compound heterozygous for variants within this gene)
PMID: 27078007 (full text not available to confirm findings).; to: Comment on publications: PMID: 25130867 (3 related cases with CAGSSS homozygous for a rare nonsynonymous variant in this gene, an unrelated case with Leigh syndrome compound heterozygous for variants within this gene)
PMID: 27078007 reports the phenotypical classification of case of Infantile Cataract, Congenital Neurotrophic Keratitis, and Orbital Myopathy in one of the cases mentioned in PMID: 25130867.
.
Mitochondrial disorders v1.397 IARS2 Sarah Leigh Added comment: Comment on publications: PMID: 25130867 (3 related cases with CAGSSS homozygous for a rare nonsynonymous variant in this gene, an unrelated case with Leigh syndrome compound heterozygous for variants within this gene)
PMID: 27078007 (full text not available to confirm findings).
Mitochondrial disorders v1.397 IARS2 Sarah Leigh Publications for gene: IARS2 were set to PMID: 25130867 (3 related cases with CAGSSS homozygous for a rare nonsynonymous variant in this gene, an unrelated case with Leigh syndrome compound heterozygous for variants within this gene); PMID: 27078007 (full text not available to confirm findings).
Cytopenias and congenital anaemias v1.70 RUNX1 Louise Daugherty Tag somatic-germline was removed from gene: RUNX1.
Tag somatic tag was added to gene: RUNX1.
Cytopenias and congenital anaemias v1.70 PIGT Louise Daugherty Tag somatic-germline was removed from gene: PIGT.
Tag somatic tag was added to gene: PIGT.
Cytopenias and congenital anaemias v1.70 PIGT Louise Daugherty Publications for gene: PIGT were set to
Cytopenias and congenital anaemias v1.69 MPL Louise Daugherty Tag somatic-germline was removed from gene: MPL.
Tag somatic tag was added to gene: MPL.
Cytopenias and congenital anaemias v1.69 IKZF1 Louise Daugherty Tag somatic-germline was removed from gene: IKZF1.
Tag somatic tag was added to gene: IKZF1.
Cytopenias and congenital anaemias v1.69 GATA2 Louise Daugherty Tag somatic-germline was removed from gene: GATA2.
Tag somatic tag was added to gene: GATA2.
Cytopenias and congenital anaemias v1.69 CEBPA Louise Daugherty Tag somatic-germline was removed from gene: CEBPA.
Tag somatic tag was added to gene: CEBPA.
Early onset or syndromic epilepsy v1.71 RRM2B Rebecca Foulger Classified gene: RRM2B as Amber List (moderate evidence)
Early onset or syndromic epilepsy v1.71 RRM2B Rebecca Foulger Added comment: Comment on list classification: Kept rating as Amber after reviewing the literature evidence. The main phenotype manifests as hypotonia with lactic acidosis. Although seizures have been reported, they are variable and not common (PMID:29241262 summary records seizures in 6/78 patients, PMID:18504129 don't report seizures in any of their three patients).
Early onset or syndromic epilepsy v1.71 RRM2B Rebecca Foulger Gene: rrm2b has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v1.70 RRM2B Rebecca Foulger Publications for gene: RRM2B were set to
Early onset or syndromic epilepsy v1.69 RRM2B Rebecca Foulger Phenotypes for gene: RRM2B were changed from Mitochondrial DNA depletion syndrome 8A (encephalomyopathic type with renal tubulopathy), 612075; seizures to Mitochondrial DNA depletion syndrome 8A (encephalomyopathic type with renal tubulopathy), 612075; seizures; status epilepticus
Early onset or syndromic epilepsy v1.68 RRM2B Rebecca Foulger commented on gene: RRM2B: Bourdon et al., 2007 (PMID:17486094) studied 7 cases of mitochondrial depletion in 4 unrelated families with RRM2B variants. Seizures were reported in Family 2: Subject 4 showed trunk hypotonia and tubulopathy shortly after birth. At 20 days of life he developed seizures, and died at 2 months after status epilepticus. His sister (Subject 5) had a similar clinical course (the authors don't explicitly state whether she had seizures).
Early onset or syndromic epilepsy v1.68 RRM2B Rebecca Foulger changed review comment from: PMID:19138848 report two Sudanese brothers with a severe form of fatal autosomal recessive encephalomyopathic mtDNA depletion syndrome-8B caused by a homozygous mutation in the RRM2B gene. Both brothers had seizures amongst their phenotypes.; to: PMID:19138848 (Kollberg et al., 2009) report two Sudanese brothers with a severe form of fatal autosomal recessive encephalomyopathic mtDNA depletion syndrome-8B caused by a homozygous mutation in the RRM2B gene. Both brothers had seizures amongst their phenotypes.
Early onset or syndromic epilepsy v1.68 RRM2B Rebecca Foulger Phenotypes for gene: RRM2B were changed from to Mitochondrial DNA depletion syndrome 8A (encephalomyopathic type with renal tubulopathy), 612075; seizures
Early onset or syndromic epilepsy v1.67 RRM2B Rebecca Foulger Mode of inheritance for gene: RRM2B was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v1.66 RRM2B Rebecca Foulger commented on gene: RRM2B: Bornstein et al., 2008 (PMID:18504129) sequenced the RRM2B gene in 3 unrelated cases- The common clinical feature was myopathy with lactic acidosis, and none had overt seizures.
Early onset or syndromic epilepsy v1.66 RRM2B Rebecca Foulger commented on gene: RRM2B: PMID:19138848 report two Sudanese brothers with a severe form of fatal autosomal recessive encephalomyopathic mtDNA depletion syndrome-8B caused by a homozygous mutation in the RRM2B gene. Both brothers had seizures amongst their phenotypes.
Early onset or syndromic epilepsy v1.66 CUX2 Rebecca Foulger Phenotypes for gene: CUX2 were changed from Seizures; Intellectual disability; Autistic behavior; Developmental epileptic encephalopathy to Seizures; Epileptic encephalopathy, early infantile, 67, 618141; Infantile onset myoclonic epileptic encephalopathy
Early onset or syndromic epilepsy v1.65 CUX2 Rebecca Foulger Classified gene: CUX2 as Green List (high evidence)
Early onset or syndromic epilepsy v1.65 CUX2 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green following discussion with Sarah Leigh. A personal communication from the authors of PMID:29630738 confirm that the variants seen in 9 patients were de novo and therefore not Founder effect. Although there is no functional data and there is limited information about the patients in PMIDs:29630738, 23020937 and 23934111, overall there are sufficient cases (10 individuals from 4 papers including 2 large-scale studies) and 2 Green reviews to support inclusion on the panel as a Green gene. Plus CUX2 is now associated with an EIEE disorder in OMIM.
Early onset or syndromic epilepsy v1.65 CUX2 Rebecca Foulger Gene: cux2 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v1.64 CUX2 Rebecca Foulger commented on gene: CUX2: A summary of evidence: ONE variant (Glu590Lys) reported from 9 patients in Chatron et al., 2018 (PMID:29630738) and 1 patient in Barington et al., 2018 (PMID:29795476). Barington et al claim their Danish patient is a third case as there are additionally two large scale reports from Rauch et al., 2012 (PMID:23020937) and the Epi4K Consortium (Allen et al., 2013, PMID:23934111)- there is sparse information about the patients in the large-scale papers, although the Epi4K patient is a German male. Two of the 9 patients in Chatron et al came from these large-scale studies. None of the papers perform functional studies. CUX2 was previously rated Amber as there was a question mark over the relatedness of patients in Chatron et al (this has been addressed by a pers.comm from Gemma Carvill).
Early onset or syndromic epilepsy v1.64 CUX2 Rebecca Foulger commented on gene: CUX2: Re-assessing the rating of CUX2 following a new Green review by Deb Pals (the new review contains the same paper (PMID:29630738) as described by Konstantinos Varvagiannis). CUX2 is now associated with an OMIM disorder: Epileptic encephalopathy, early infantile, 67, 618141. The DD-Gene2Phenotype rating is still probable.
Early onset or syndromic epilepsy v1.64 CUX2 Rebecca Foulger commented on gene: CUX2
Early onset or syndromic epilepsy v1.64 RRM2B Rebecca Foulger commented on gene: RRM2B
Intellectual disability v2.881 BRD4 Ivone Leong Classified gene: BRD4 as Green List (high evidence)
Intellectual disability v2.881 BRD4 Ivone Leong Added comment: Comment on list classification: New gene added by external expert and reviewed by curation team. Promoted from red to green based on the evidence provided by Konstantinos Varvagiannis (Other). BRD4 is not associated with a phenotype in OMIM and in Gene2Phenotype it is reported to be probably associated with Cornelia de Lange-like syndrome. Intellectual disability (medium to severe) is a phenotype of Cornelia de Lange-like syndrome.
Intellectual disability v2.881 BRD4 Ivone Leong Gene: brd4 has been classified as Green List (High Evidence).
Limb disorders v1.7 SOX9 Louise Daugherty Tag duplication was removed from gene: SOX9.
Tag gene-duplication tag was added to gene: SOX9.
Intellectual disability v2.880 SETD1B Ivone Leong Classified gene: SETD1B as Green List (high evidence)
Intellectual disability v2.880 SETD1B Ivone Leong Added comment: Comment on list classification: Promoted from amber to green as there is now sufficient evidence to support a gene-disease association, based on submitted reviews.
Intellectual disability v2.880 SETD1B Ivone Leong Gene: setd1b has been classified as Green List (High Evidence).
Intellectual disability v2.879 SETD1B Ivone Leong Publications for gene: SETD1B were set to 29322246; 27106595; 25428890
Intellectual disability v2.878 SETD1B Ivone Leong reviewed gene: SETD1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 31110234; Phenotypes: ; Mode of inheritance: None
Hereditary haemorrhagic telangiectasia v1.44 EPHB4 Claire Shovlin reviewed gene: EPHB4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28687708 PMID: 30760892; Phenotypes: capillary malformation, epistaxis, telangiectasia, cerebral AVM; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Proteinuric renal disease v1.189 COL4A1 Eleanor Williams Phenotypes for gene: COL4A1 were changed from to Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps #611773
Proteinuric renal disease v1.188 COL4A1 Eleanor Williams Publications for gene: COL4A1 were set to
Proteinuric renal disease v1.187 CDK20 Eleanor Williams Phenotypes for gene: CDK20 were changed from to Chronic kidney disease
Proteinuric renal disease v1.186 CDK20 Eleanor Williams Publications for gene: CDK20 were set to
Proteinuric renal disease v1.185 CD151 Eleanor Williams Phenotypes for gene: CD151 were changed from to Nephropathy with pretibial epidermolysis bullosa and deafness #609057
Proteinuric renal disease v1.184 CD151 Eleanor Williams Publications for gene: CD151 were set to
Proteinuric renal disease v1.183 ARHGAP24 Eleanor Williams Phenotypes for gene: ARHGAP24 were changed from to Focal segmental glomerulosclerosis
Proteinuric renal disease v1.182 ARHGAP24 Eleanor Williams Publications for gene: ARHGAP24 were set to
Proteinuric renal disease v1.181 ANKFY1 Eleanor Williams Publications for gene: ANKFY1 were set to
Proteinuric renal disease v1.180 ZMPSTE24 Eleanor Williams Phenotypes for gene: ZMPSTE24 were changed from to Mandibuloacral dysplasia with type B lipodystrophy #608612
Proteinuric renal disease v1.179 ZMPSTE24 Eleanor Williams Publications for gene: ZMPSTE24 were set to
Proteinuric renal disease v1.178 VPS33B Eleanor Williams Phenotypes for gene: VPS33B were changed from to Arthrogryposis, renal dysfunction, and cholestasis 1 #208085
Proteinuric renal disease v1.177 VPS33B Eleanor Williams Publications for gene: VPS33B were set to
Proteinuric renal disease v1.176 VIPAS39 Eleanor Williams Phenotypes for gene: VIPAS39 were changed from to Arthrogryposis, renal dysfunction, and cholestasis 2 # 613404
Proteinuric renal disease v1.175 VIPAS39 Eleanor Williams Publications for gene: VIPAS39 were set to
Proteinuric renal disease v1.174 TTC21B Eleanor Williams Phenotypes for gene: TTC21B were changed from to Nephronophthisis 12 # 613820
Proteinuric renal disease v1.173 TTC21B Eleanor Williams Publications for gene: TTC21B were set to
Proteinuric renal disease v1.172 TPRKB Eleanor Williams Phenotypes for gene: TPRKB were changed from to Galloway-Mowat syndrome 5 #617731
Proteinuric renal disease v1.171 TPRKB Eleanor Williams Publications for gene: TPRKB were set to
Proteinuric renal disease v1.170 SYNPO Eleanor Williams Phenotypes for gene: SYNPO were changed from to Focal segmental glomerulosclerosis; FSGS
Proteinuric renal disease v1.169 SYNPO Eleanor Williams Publications for gene: SYNPO were set to
Proteinuric renal disease v1.168 PTPRO Eleanor Williams Phenotypes for gene: PTPRO were changed from to Nephrotic syndrome, type 6 #614196
Proteinuric renal disease v1.167 PTPRO Eleanor Williams Publications for gene: PTPRO were set to
Proteinuric renal disease v1.166 PMM2 Eleanor Williams Phenotypes for gene: PMM2 were changed from to Congenital disorder of glycosylation, type Ia #212065
Proteinuric renal disease v1.165 PMM2 Eleanor Williams Publications for gene: PMM2 were set to
Proteinuric renal disease v1.164 NUP205 Eleanor Williams Phenotypes for gene: NUP205 were changed from to ?Nephrotic syndrome, type 13 #616893
Proteinuric renal disease v1.163 NUP205 Eleanor Williams Publications for gene: NUP205 were set to
Proteinuric renal disease v1.162 NUP160 Eleanor Williams Phenotypes for gene: NUP160 were changed from to ?Nephrotic syndrome, type 19 #618178
Proteinuric renal disease v1.161 NUP160 Eleanor Williams Publications for gene: NUP160 were set to
Proteinuric renal disease v1.160 NPHP4 Eleanor Williams Phenotypes for gene: NPHP4 were changed from to Nephronophthisis 4 #606966
Proteinuric renal disease v1.159 NPHP4 Eleanor Williams Publications for gene: NPHP4 were set to
Proteinuric renal disease v1.158 MEFV Eleanor Williams Phenotypes for gene: MEFV were changed from to Familial Mediterranean fever, AR #249100
Proteinuric renal disease v1.157 MAFB Eleanor Williams Phenotypes for gene: MAFB were changed from to FSGS with Duane retraction syndrome
Proteinuric renal disease v1.156 MAFB Eleanor Williams Publications for gene: MAFB were set to
Proteinuric renal disease v1.155 LMNA Eleanor Williams Phenotypes for gene: LMNA were changed from to Partial lipodystrophy and FSGS
Proteinuric renal disease v1.154 LMNA Eleanor Williams Publications for gene: LMNA were set to
Proteinuric renal disease v1.153 LCAT Eleanor Williams Phenotypes for gene: LCAT were changed from to Norum disease #245900
Proteinuric renal disease v1.152 KANK2 Eleanor Williams Phenotypes for gene: KANK2 were changed from Early-Childhood-Onset Steroid-Resistant Nephrotic Syndrome to Early-Childhood-Onset Steroid-Resistant Nephrotic Syndrome; Nephrotic syndrome 16 #617783
Proteinuric renal disease v1.151 KANK2 Eleanor Williams Publications for gene: KANK2 were set to J Clin Invest. 2015; 125(6):2375–2384
Proteinuric renal disease v1.150 ITSN2 Eleanor Williams Phenotypes for gene: ITSN2 were changed from to Early childhood SSNS
Proteinuric renal disease v1.149 ITSN2 Eleanor Williams Publications for gene: ITSN2 were set to
Proteinuric renal disease v1.148 ITGB4 Eleanor Williams Phenotypes for gene: ITGB4 were changed from to Epidermolysis bullosa, junctional, with pyloric stenosis #226730
Proteinuric renal disease v1.147 ITGB4 Eleanor Williams Publications for gene: ITGB4 were set to
Proteinuric renal disease v1.146 ITGA3 Eleanor Williams Phenotypes for gene: ITGA3 were changed from to Interstitial lung disease, nephrotic syndrome, and epidermolysis bullosa, congenital #614748
Proteinuric renal disease v1.145 GAPVD1 Eleanor Williams Publications for gene: GAPVD1 were set to
Proteinuric renal disease v1.144 DGKE Eleanor Williams Phenotypes for gene: DGKE were changed from to Nephrotic syndrome, type 7 #615008
Proteinuric renal disease v1.143 DGKE Eleanor Williams Publications for gene: DGKE were set to
Proteinuric renal disease v1.142 CD2AP Eleanor Williams Phenotypes for gene: CD2AP were changed from to Glomerulosclerosis, focal segmental, 3 #607832
Proteinuric renal disease v1.141 CD2AP Eleanor Williams Publications for gene: CD2AP were set to
Proteinuric renal disease v1.140 ARHGDIA Eleanor Williams Phenotypes for gene: ARHGDIA were changed from to Nephrotic syndrome, type 8 #615224
Proteinuric renal disease v1.139 ARHGDIA Eleanor Williams Publications for gene: ARHGDIA were set to
Hereditary neuropathy v1.331 AP1S1 Alexander Rossor edited their review of gene: AP1S1: Added comment: Same homozygous mutation described in 4 families form same geographical region; Changed rating: AMBER
Hereditary neuropathy v1.331 XRCC1 Alexander Rossor edited their review of gene: XRCC1: Added comment: Only two families; Changed rating: AMBER; Changed publications: 29472272, 28002403
Hereditary neuropathy v1.331 SCYL1 Alexander Rossor edited their review of gene: SCYL1: Added comment: Neuropthay only in 2 unrelated patients; Changed rating: AMBER; Changed publications: 26581903, 30258122
Hereditary neuropathy v1.331 DNAJB2 Alexander Rossor edited their review of gene: DNAJB2: Added comment: Multiple families now reported with recessive CMT/ HMN. PMIDs added above; Changed publications: 26752306, 25274842, 22522442
Structural eye disease v0.83 SCLT1 Ivone Leong Publications for gene: SCLT1 were set to 29450879; 24285566; 27894351; 28486600; 30425282; 30237576; 24285566; 29450879
Structural eye disease v0.82 SCLT1 Ivone Leong Publications for gene: SCLT1 were set to 29450879; 24285566; 27894351; 28486600
Structural eye disease v0.81 KIAA0586 Ivone Leong reviewed gene: KIAA0586: Rating: AMBER; Mode of pathogenicity: ; Publications: 30055837; Phenotypes: ; Mode of inheritance:
Structural eye disease v0.81 SCLT1 Anna de Burca reviewed gene: SCLT1: Rating: AMBER; Mode of pathogenicity: ; Publications: 30425282, 30237576, 24285566, 29450879; Phenotypes: ; Mode of inheritance:
Structural eye disease v0.80 KIAA0586 Ivone Leong gene: KIAA0586 was added
gene: KIAA0586 was added to Structural eye disease. Sources: Expert list,Expert Review Amber
Mode of inheritance for gene: KIAA0586 was set to
Publications for gene: KIAA0586 were set to 30055837
Structural eye disease v0.80 SCLT1 Ivone Leong Source Expert Review Amber was added to SCLT1.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Structural eye disease v0.79 TMEM237 Ivone Leong Classified gene: TMEM237 as Green List (high evidence)
Structural eye disease v0.79 TMEM237 Ivone Leong Added comment: Comment on list classification: Promoted from amber to green based on expert review.
Structural eye disease v0.79 TMEM237 Ivone Leong Gene: tmem237 has been classified as Green List (High Evidence).
Structural eye disease v0.78 TMEM216 Ivone Leong Classified gene: TMEM216 as Green List (high evidence)
Structural eye disease v0.78 TMEM216 Ivone Leong Added comment: Comment on list classification: Promoted from amber to green based on expert review.
Structural eye disease v0.78 TMEM216 Ivone Leong Gene: tmem216 has been classified as Green List (High Evidence).
Hereditary haemorrhagic telangiectasia v1.44 EPHB4 Ellen Thomas Classified gene: EPHB4 as Amber List (moderate evidence)
Hereditary haemorrhagic telangiectasia v1.44 EPHB4 Ellen Thomas Gene: ephb4 has been classified as Amber List (Moderate Evidence).
Hereditary haemorrhagic telangiectasia v1.43 EPHB4 Ellen Thomas gene: EPHB4 was added
gene: EPHB4 was added to Hereditary haemorrhagic telangiectasia. Sources: Other
Mode of inheritance for gene: EPHB4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EPHB4 were set to 28687708; 28730721
Phenotypes for gene: EPHB4 were set to Capillary malformation-arteriovenous malformation 2; 618196
Penetrance for gene: EPHB4 were set to Incomplete
Review for gene: EPHB4 was set to AMBER
Added comment: At least one family in 100k recruited under HHT has a mutation in this gene as it's an overlap condition. Consider whether to include with the GLH specialist group for GMS diagnostic analysis.
Sources: Other
Hereditary neuropathy v1.331 Louise Daugherty removed STR:NOP56_GGCCTGTT from the panel
Rare multisystem ciliopathy disorders v1.114 POC1B Eleanor Williams Phenotypes for gene: POC1B were changed from Joubert Syndrome and Senior-Loken Syndrome 24 gene panel to Joubert Syndrome; Senior-Loken Syndrome 24 gene panel; Cone-rod dystrophy 20 615973; AUTOSOMAL-RECESSIVE CONE-ROD DYSTROPHY
Rare multisystem ciliopathy disorders v1.113 POC1B Eleanor Williams Publications for gene: POC1B were set to
Rare multisystem ciliopathy disorders v1.112 POC1B Eleanor Williams Classified gene: POC1B as Amber List (moderate evidence)
Rare multisystem ciliopathy disorders v1.112 POC1B Eleanor Williams Added comment: Comment on list classification: Multiple cases of a single feature (retinal dystrophy) disease, only one case plus disease model for multisystem ciliopathy. Rating Amber.
Rare multisystem ciliopathy disorders v1.112 POC1B Eleanor Williams Gene: poc1b has been classified as Amber List (Moderate Evidence).
Rare multisystem ciliopathy disorders v1.111 POC1B Eleanor Williams commented on gene: POC1B
Rare multisystem ciliopathy disorders v1.111 ALMS1 Rebecca Foulger changed review comment from: Addressed Red review from Beth Hoskins, imported from Bardet-Biedl Syndrome panel. ALMS1 is appropriate for this panel: Confirmed DDG2P gene for ALSTROM SYNDROME (a Ciliopathy) and sufficient cases from the literature/OMIM to support inclusion.; to: Addressing Red review from Beth Hoskins, imported from Bardet-Biedl Syndrome panel: ALMS1 is appropriate for this panel: Confirmed DDG2P gene for ALSTROM SYNDROME (a Ciliopathy) and sufficient cases from the literature/OMIM to support inclusion.
Rare multisystem ciliopathy disorders v1.111 ALMS1 Rebecca Foulger commented on gene: ALMS1
Rare multisystem ciliopathy disorders v1.111 TMEM67 Rebecca Foulger commented on gene: TMEM67
Rare multisystem ciliopathy disorders v1.111 PKD1 Rebecca Foulger Phenotypes for gene: PKD1 were changed from Polycystic kidney disease, adult type I, 173900 to Polycystic kidney disease, adult type I, 173900; Autosomal recessive polycystic kidney disease (ARPKD); Autosomal dominant polycystic kidney disease (ADPKD)
Rare multisystem ciliopathy disorders v1.110 PKD1 Rebecca Foulger Added comment: Comment on mode of inheritance: Updated MOI from Monoallelic to both Monoallelic and Biallelic, based on review by Julia Baptista.
Rare multisystem ciliopathy disorders v1.110 PKD1 Rebecca Foulger Mode of inheritance for gene: PKD1 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
Rare multisystem ciliopathy disorders v1.109 PKD1 Rebecca Foulger Publications for gene: PKD1 were set to
Rare multisystem ciliopathy disorders v1.108 IFT43 Rebecca Foulger changed review comment from: Comment on list classification: Updated rating from Amber to Green based on two Green reviews from Penny Clouston and Zornitza Stark. Sufficient cases in the literature to support inclusion on the Ciliopathy panel, including two cases of short-rib thoracic dysplasia with polydactyly from PMID:28400947. Plus confirmed rating in DDG2P for CRANIOECTODERMAL DYSPLASIA TYPE 3; CED3 (also known as Sensenbrenner syndrome) is a rare autosomal recessive heterogeneous ciliopathy. Plus functional information with IFT43 involved in ciliary transport.; to: Comment on list classification: Updated rating from Amber to Green based on two Green reviews from Penny Clouston and Zornitza Stark. Sufficient cases in the literature to support inclusion on the Ciliopathy panel, including two cases of short-rib thoracic dysplasia with polydactyly from PMID:28400947. Plus confirmed rating in DDG2P for CRANIOECTODERMAL DYSPLASIA TYPE 3; CED3 (also known as Sensenbrenner syndrome) is a rare autosomal recessive heterogeneous ciliopathy. Plus functional role with IFT43 involved in ciliary transport.
Rare multisystem ciliopathy disorders v1.108 IFT43 Rebecca Foulger changed review comment from: Comment on list classification: Updated rating from Amber to Green based on two Green reviews from Penny Clouston and Zornitza Stark. Sufficient cases in the literature to support inclusion on the Ciliopathy panel, including two cases of short-rib thoracic dysplasia with polydactyly from PMID:28400947. Plus confirmed rating in DDG2P for CRANIOECTODERMAL DYSPLASIA TYPE 3; CED3 (also known as Sensenbrenner syndrome) is a rare autosomal recessive heterogeneous ciliopathy.; to: Comment on list classification: Updated rating from Amber to Green based on two Green reviews from Penny Clouston and Zornitza Stark. Sufficient cases in the literature to support inclusion on the Ciliopathy panel, including two cases of short-rib thoracic dysplasia with polydactyly from PMID:28400947. Plus confirmed rating in DDG2P for CRANIOECTODERMAL DYSPLASIA TYPE 3; CED3 (also known as Sensenbrenner syndrome) is a rare autosomal recessive heterogeneous ciliopathy. Plus functional information with IFT43 involved in ciliary transport.
Rare multisystem ciliopathy disorders v1.108 IFT43 Rebecca Foulger Phenotypes for gene: IFT43 were changed from Short-rib thoracic dysplasia 18 with polydactyly, 617866; Cranioectodermal dysplasia 3, 614099; Sensenbrenner syndrome to Short-rib thoracic dysplasia 18 with polydactyly, 617866; Cranioectodermal dysplasia 3, 614099; Sensenbrenner syndrome
Rare multisystem ciliopathy disorders v1.108 IFT43 Rebecca Foulger Phenotypes for gene: IFT43 were changed from Short-rib thoracic dysplasia 18 with polydactyly, 617866; Sensenbrenner syndrome to Short-rib thoracic dysplasia 18 with polydactyly, 617866; Cranioectodermal dysplasia 3, 614099; Sensenbrenner syndrome
Rare multisystem ciliopathy disorders v1.107 IFT43 Rebecca Foulger changed review comment from: Comment on list classification: Updated rating from Amber to Green based on two Green reviews from Penny Clouston and Zornitza Stark. Sufficient cases in the literature to support inclusion on the Ciliopathy panel.; to: Comment on list classification: Updated rating from Amber to Green based on two Green reviews from Penny Clouston and Zornitza Stark. Sufficient cases in the literature to support inclusion on the Ciliopathy panel, including two cases of short-rib thoracic dysplasia with polydactyly from PMID:28400947. Plus confirmed rating in DDG2P for CRANIOECTODERMAL DYSPLASIA TYPE 3; CED3 (also known as Sensenbrenner syndrome) is a rare autosomal recessive heterogeneous ciliopathy.
Rare multisystem ciliopathy disorders v1.107 IFT43 Rebecca Foulger Phenotypes for gene: IFT43 were changed from Cranioectodermal dysplasia 3, 614099; Short-rib polydactyly syndrome; Sensenbrenner syndrome to Short-rib thoracic dysplasia 18 with polydactyly, 617866; Sensenbrenner syndrome
Rare multisystem ciliopathy disorders v1.106 IFT81 Rebecca Foulger commented on gene: IFT81: Added watchlist tag.
Rare multisystem ciliopathy disorders v1.106 IFT81 Rebecca Foulger Tag watchlist tag was added to gene: IFT81.
Rare multisystem ciliopathy disorders v1.106 IFT81 Rebecca Foulger Classified gene: IFT81 as Amber List (moderate evidence)
Rare multisystem ciliopathy disorders v1.106 IFT81 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Red to Amber. Associated with OMIM:617895 but not yet associated with a disorder in Gene2Phenotype. Functional data supports a ciliopathy association: IFT81 is part of the IFT-B complex involved in the bidirectional transport of ciliary proteins. Green review from Zornitza based on 3 (or 4) individuals identified in the literature with a Cliopathy phenotype and biallelic IFT81 variants. However in the two cases from PMID:26275418, OMIM classes the variants as VUS. Therefore on balance have classed as Amber awaiting further cases or clarification of the variants in PMID:26275418.
Rare multisystem ciliopathy disorders v1.106 IFT81 Rebecca Foulger Gene: ift81 has been classified as Amber List (Moderate Evidence).
Rare multisystem ciliopathy disorders v1.105 IFT81 Rebecca Foulger commented on gene: IFT81: Duran et al. 2016 (PMID:27666822) identify two individuals with skeletal ciliopathies: R98-443 with sphyxiating thoracic dystrophy (ATD), and R13-147A with Short-rib polydactyly syndromes (SRPS). Exome sequencing revealed compound het variants in IFT81 in both cases: p.Leu29Phe and p.Arg512* in R98-443, and p.Leu262* and p.Leu435del in R13-147A.
Rare multisystem ciliopathy disorders v1.105 IFT81 Rebecca Foulger changed review comment from: Perrault et al., 2015 (PMID:26275418) screened 1628 individuals with reno-ocular ciliopathies by sequencing of ciliary candidate genes and identified recessive ITF81 variants in two consanguineous families with a ciliopathy phenotype.
They identified a homozygous variant in IFT81 in one individual (A3286-21) with a nephronophthisis-related ciliopathy, polydactyly and moderate intellectual disability (delayed speech and an IQ of 70). They identified a loss-of-stop variant in IFT81 in a second individual (NCK-033) with neuronal ceroid lipofuscinosis-1. This proband presented with retinal dystrophy (RD), brain lesions and mild intellectual disability. The patient also harboured 9 additional rare homozygous variants including a missense change (Gly245Arg) in the gene PPT1, accounting for the clinical diagnosis of neuronal ceroid lipofuscinosis-1. Both these variants have currently been classed as VUS in OMIM.; to: Perrault et al., 2015 (PMID:26275418) screened 1628 individuals with reno-ocular ciliopathies by sequencing of ciliary candidate genes and identified recessive ITF81 variants in two consanguineous families with a ciliopathy phenotype.
They identified a homozygous variant in IFT81 in one individual (A3286-21) with a nephronophthisis-related ciliopathy, polydactyly and moderate intellectual disability (delayed speech and an IQ of 70). They identified a loss-of-stop variant in IFT81 in a second individual (NCK-033) with neuronal ceroid lipofuscinosis-1. This proband presented with retinal dystrophy (RD), brain lesions and mild intellectual disability. The patient also harboured 9 additional rare homozygous variants including a missense change (Gly245Arg) in the gene PPT1, accounting for the clinical diagnosis of neuronal ceroid lipofuscinosis-1. Both these variants have currently been classed as VUS in OMIM.
Rare multisystem ciliopathy disorders v1.105 IFT81 Rebecca Foulger commented on gene: IFT81
Rare multisystem ciliopathy disorders v1.105 IFT81 Rebecca Foulger Mode of inheritance for gene: IFT81 was changed from to BIALLELIC, autosomal or pseudoautosomal
Rare multisystem ciliopathy disorders v1.104 IFT81 Rebecca Foulger Phenotypes for gene: IFT81 were changed from to Short-rib thoracic dysplasia 19 with or without polydactyly, 617895
Rare multisystem ciliopathy disorders v1.103 IFT81 Rebecca Foulger Publications for gene: IFT81 were set to
Hereditary neuropathy v1.330 Louise Daugherty removed STR:NOP56_GGCCTGTT from the panel
Hereditary neuropathy v1.329 NOP56_GGCCTGTT Louise Daugherty Classified STR: NOP56_GGCCTGTT as No list
Hereditary neuropathy v1.329 NOP56_GGCCTGTT Louise Daugherty Added comment: Comment on list classification: this is a test -
Hereditary neuropathy v1.329 NOP56_GGCCTGTT Louise Daugherty Str: nop56_ggcctgtt has been removed from the panel.
Hereditary neuropathy v1.328 Louise Daugherty removed STR:NOP56_GGCCTGTT from the panel
Hereditary neuropathy v1.327 NOP56_GGCCTGTT Louise Daugherty Classified STR: NOP56_GGCCTGTT as Red List (low evidence)
Hereditary neuropathy v1.327 NOP56_GGCCTGTT Louise Daugherty Str: nop56_ggcctgtt has been classified as Red List (Low Evidence).
Hereditary neuropathy v1.326 Louise Daugherty removed STR:NOP56_GGCCTGTT from the panel
Hereditary neuropathy v1.325 NOP56_GGCCTGTT Louise Daugherty Classified STR: NOP56_GGCCTGTT as No list
Hereditary neuropathy v1.325 NOP56_GGCCTGTT Louise Daugherty Str: nop56_ggcctgtt has been removed from the panel.
Hereditary neuropathy v1.324 Louise Daugherty removed STR:NOP56_GGCCTGTT from the panel
Hereditary neuropathy v1.322 Louise Daugherty removed STR:NOP56_GGCCTGTT from the panel
Intellectual disability v2.878 COL4A3BP Louise Daugherty commented on gene: COL4A3BP
DDG2P v1.68 COL4A3BP Louise Daugherty commented on gene: COL4A3BP
Fetal anomalies v0.285 COL4A3BP Louise Daugherty commented on gene: COL4A3BP
Fetal anomalies v0.285 COL4A3BP Louise Daugherty Tag new-gene-name tag was added to gene: COL4A3BP.
DDG2P v1.68 COL4A3BP Louise Daugherty Tag new-gene-name tag was added to gene: COL4A3BP.
Intellectual disability v2.878 COL4A3BP Louise Daugherty Tag new-gene-name tag was added to gene: COL4A3BP.
Proteinuric renal disease v1.137 APOL1 Eleanor Williams Phenotypes for gene: APOL1 were changed from to Focal Segmental Glomerulosclerosis 4, Susceptibility to #612551
Proteinuric renal disease v1.136 APOL1 Eleanor Williams Publications for gene: APOL1 were set to
Proteinuric renal disease v1.135 ANLN Eleanor Williams Publications for gene: ANLN were set to 24676636
Proteinuric renal disease v1.134 AMN Eleanor Williams Publications for gene: AMN were set to 12590260
Proteinuric renal disease v1.133 ALMS1 Eleanor Williams Phenotypes for gene: ALMS1 were changed from to Alstrom Syndrome #203800
Proteinuric renal disease v1.132 ALMS1 Eleanor Williams Publications for gene: ALMS1 were set to
Proteinuric renal disease v1.131 ALG1 Eleanor Williams Phenotypes for gene: ALG1 were changed from to Congenital disorder of glycosylation, type Ik #608540
Proteinuric renal disease v1.130 ALG1 Eleanor Williams Publications for gene: ALG1 were set to
Proteinuric renal disease v1.129 WT1 Eleanor Williams Phenotypes for gene: WT1 were changed from to Denys-Drash syndrome #194080; Frasier syndrome #136680; Wilms tumor, type 1 #194070
Proteinuric renal disease v1.128 WT1 Eleanor Williams Publications for gene: WT1 were set to
Proteinuric renal disease v1.127 WDR73 Eleanor Williams Phenotypes for gene: WDR73 were changed from to Galloway-Mowat syndrome 1 #251300
Proteinuric renal disease v1.126 WDR73 Eleanor Williams Publications for gene: WDR73 were set to
Proteinuric renal disease v1.125 TRPC6 Eleanor Williams Phenotypes for gene: TRPC6 were changed from to Glomerulosclerosis, focal segmental, 2 #603652; Proteinuria; FSGS; kidney failure; Familial and sporadic SRNS (adult)
Proteinuric renal disease v1.124 TRPC6 Eleanor Williams Publications for gene: TRPC6 were set to
Proteinuric renal disease v1.123 SMARCAL1 Eleanor Williams Phenotypes for gene: SMARCAL1 were changed from to Schimke immunoosseous dysplasia #242900
Proteinuric renal disease v1.122 SMARCAL1 Eleanor Williams Publications for gene: SMARCAL1 were set to
Proteinuric renal disease v1.121 SCARB2 Eleanor Williams Phenotypes for gene: SCARB2 were changed from to Action myoclonus renal failure syndrome; Epilepsy, progressive myoclonic 4, with or without renal failure #254900
Proteinuric renal disease v1.120 SCARB2 Eleanor Williams Publications for gene: SCARB2 were set to
Proteinuric renal disease v1.119 PLCE1 Eleanor Williams Phenotypes for gene: PLCE1 were changed from to Nephrotic syndrome, type 3 #610725; Congenital nephrotic syndrome/SRNS
Proteinuric renal disease v1.118 PLCE1 Eleanor Williams Publications for gene: PLCE1 were set to
Proteinuric renal disease v1.117 PDSS2 Eleanor Williams Phenotypes for gene: PDSS2 were changed from to Coenzyme Q10 deficiency, primary, 3 #614652; Leigh syndrome
Proteinuric renal disease v1.116 PDSS2 Eleanor Williams Publications for gene: PDSS2 were set to
Proteinuric renal disease v1.115 NUP93 Eleanor Williams Phenotypes for gene: NUP93 were changed from Early-Childhood-Onset Steroid-Resistant Nephrotic Syndrome to Early-Childhood-Onset Steroid-Resistant Nephrotic Syndrome; Nephrotic syndrome, type 12 #616892
Proteinuric renal disease v1.114 NUP93 Eleanor Williams Publications for gene: NUP93 were set to Am J Hum Genet. 2015 Oct 1; 97(4):555-66
Proteinuric renal disease v1.113 NPHS2 Eleanor Williams Phenotypes for gene: NPHS2 were changed from to Nephrotic syndrome, type 2 #600995
Proteinuric renal disease v1.112 NPHS1 Eleanor Williams Phenotypes for gene: NPHS1 were changed from to Nephrotic syndrome, type 1 #602716
Proteinuric renal disease v1.111 MYO1E Eleanor Williams Phenotypes for gene: MYO1E were changed from to Glomerulosclerosis, focal segmental, 6 #614131
Proteinuric renal disease v1.110 MYO1E Eleanor Williams Publications for gene: MYO1E were set to PMID: 21697813
Proteinuric renal disease v1.109 MYH9 Eleanor Williams Phenotypes for gene: MYH9 were changed from to Epstein syndrome #153650; Fechtner syndrome #153640
Proteinuric renal disease v1.108 MYH9 Eleanor Williams Publications for gene: MYH9 were set to
Hereditary ataxia, adult onset v1.171 MSTO1 Louise Daugherty Deleted their comment
Hereditary ataxia, adult onset v1.171 PIK3R5 Louise Daugherty edited their review of gene: PIK3R5: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels -Hereditary ataxia v1.148 - Brain channelopathy v1.46. This gene was RED and external expert review from London North GLH and Wessex and West Midlands GLH for GMS Neurology specialist test group for R54 agrees this gene should remain RED; Changed rating: RED
Hereditary ataxia, adult onset v1.171 PI4KA Louise Daugherty edited their review of gene: PI4KA: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels -Hereditary ataxia v1.148 - Brain channelopathy v1.46. This gene was RED and external expert review from Wessex and West Midlands GLH for GMS Neurology specialist test group for R54 agrees this gene should remain RED; Changed rating: RED
Hereditary ataxia, adult onset v1.171 PCLO Louise Daugherty edited their review of gene: PCLO: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels -Hereditary ataxia v1.148 - Brain channelopathy v1.46. This gene was RED and external expert review from Wessex and West Midlands GLH for GMS Neurology specialist test group for R54 agrees this gene should remain RED; Changed rating: RED
Hereditary ataxia, adult onset v1.171 SMPD4 Louise Daugherty edited their review of gene: SMPD4: Changed rating: AMBER
Hereditary ataxia, adult onset v1.171 MME Louise Daugherty edited their review of gene: MME: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels -Hereditary ataxia v1.148 - Brain channelopathy v1.46. This gene was RED and external expert review from Wessex and West Midlands GLH and London North GLH for GMS Neurology specialist test group for R54 agrees this gene should remain RED; Changed rating: RED
Hereditary ataxia, adult onset v1.171 KCNK18 Louise Daugherty edited their review of gene: KCNK18: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels -Hereditary ataxia v1.148 - Brain channelopathy v1.46. This gene was RED and external expert review from Wessex and West Midlands GLH and London North GLH for GMS Neurology specialist test group for R54 agrees this gene should remain RED; Changed rating: RED
Hereditary ataxia, adult onset v1.171 CDK5 Louise Daugherty edited their review of gene: CDK5: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels -Hereditary ataxia v1.148 - Brain channelopathy v1.46. This gene was RED and external expert review from Wessex and West Midlands GLH for GMS Neurology specialist test group for R54 agrees this gene should remain RED; Changed rating: RED
Hereditary ataxia, adult onset v1.171 DCC Louise Daugherty edited their review of gene: DCC: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels -Hereditary ataxia v1.148 - Brain channelopathy v1.46. This gene was RED and external expert review from Wessex and West Midlands GLH for GMS Neurology specialist test group for R54 agrees this gene should remain RED; Changed rating: RED
Hereditary ataxia, adult onset v1.171 DMXL2 Louise Daugherty edited their review of gene: DMXL2: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels -Hereditary ataxia v1.148 - Brain channelopathy v1.46. This gene was RED and external expert review from Wessex and West Midlands GLH for GMS Neurology specialist test group for R54 agrees this gene should remain RED; Changed rating: RED
Hereditary ataxia, adult onset v1.171 FRMD4A Louise Daugherty edited their review of gene: FRMD4A: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels -Hereditary ataxia v1.148 - Brain channelopathy v1.46. This gene was RED and external expert review from Wessex and West Midlands GLH for GMS Neurology specialist test group for R54 agrees this gene should remain RED; Changed rating: RED
Hereditary ataxia, adult onset v1.171 GLI3 Louise Daugherty edited their review of gene: GLI3: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels -Hereditary ataxia v1.148 - Brain channelopathy v1.46. This gene was RED and external expert review from Wessex and West Midlands GLH for GMS Neurology specialist test group for R54 agrees this gene should remain RED; Changed rating: RED
Hereditary ataxia, adult onset v1.171 CCDC88C Louise Daugherty edited their review of gene: CCDC88C: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from London North GLH and Wessex and West Midlands GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.89 TBP Louise Daugherty edited their review of gene: TBP: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.89 TPK1 Louise Daugherty edited their review of gene: TPK1: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.89 TREM2 Louise Daugherty edited their review of gene: TREM2: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.89 TREX1 Louise Daugherty edited their review of gene: TREX1: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.89 TREX1 Louise Daugherty Mode of inheritance for gene: TREX1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Dystonia, chorea or related movement disorder, adult onset v0.88 VPS37A Louise Daugherty edited their review of gene: VPS37A: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 RNASEH2A Louise Daugherty edited their review of gene: RNASEH2A: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 RNASEH2B Louise Daugherty edited their review of gene: RNASEH2B: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 RNASEH2C Louise Daugherty edited their review of gene: RNASEH2C: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 SAMHD1 Louise Daugherty edited their review of gene: SAMHD1: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED, there is relevance only to childhood onset; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 SCN9A Louise Daugherty edited their review of gene: SCN9A: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 SCP2 Louise Daugherty edited their review of gene: SCP2: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 SDHAF1 Louise Daugherty edited their review of gene: SDHAF1: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 SLC41A1 Louise Daugherty edited their review of gene: SLC41A1: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 SLC46A1 Louise Daugherty edited their review of gene: SLC46A1: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 SNCAIP Louise Daugherty edited their review of gene: SNCAIP: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 SUOX Louise Daugherty edited their review of gene: SUOX: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED, more associated with childhood onset, which this panel does not represent.; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 PTEN Louise Daugherty edited their review of gene: PTEN: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 PSEN1 Louise Daugherty edited their review of gene: PSEN1: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 PPP2R2B Louise Daugherty edited their review of gene: PPP2R2B: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 PNPT1 Louise Daugherty edited their review of gene: PNPT1: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 PDX1 Louise Daugherty edited their review of gene: PDX1: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 PDHX Louise Daugherty edited their review of gene: PDHX: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 PCDH12 Louise Daugherty edited their review of gene: PCDH12: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 NUP62 Louise Daugherty Deleted their comment
Dystonia, chorea or related movement disorder, adult onset v0.88 NUP62 Louise Daugherty commented on gene: NUP62: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED
Dystonia, chorea or related movement disorder, adult onset v0.88 NUP62 Louise Daugherty edited their review of gene: NUP62: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 NR4A2 Louise Daugherty edited their review of gene: NR4A2: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 NPC2 Louise Daugherty edited their review of gene: NPC2: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 NDUFS3 Louise Daugherty edited their review of gene: NDUFS3: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 NDUFA9 Louise Daugherty edited their review of gene: NDUFA9: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 NDUFA2 Louise Daugherty edited their review of gene: NDUFA2: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 NDUFA12 Louise Daugherty edited their review of gene: NDUFA12: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 MR1 Louise Daugherty edited their review of gene: MR1: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 MPV17 Louise Daugherty edited their review of gene: MPV17: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 MMADHC Louise Daugherty edited their review of gene: MMADHC: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 MCOLN1 Louise Daugherty edited their review of gene: MCOLN1: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 MAT1A Louise Daugherty edited their review of gene: MAT1A: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 L2HGDH Louise Daugherty edited their review of gene: L2HGDH: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 KCNK18 Louise Daugherty edited their review of gene: KCNK18: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH and London North GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 JPH3 Louise Daugherty edited their review of gene: JPH3: Added comment: This gene was uploaded from the curation template sent out to the GLHs for GMS Neurology specialist test group as it is a RED gene on the Parkinson Disease and Complex Parkinsonism panel. It relates to the STR JPH3_CTG (rated GREEN) and not the gene entity, as there are no SNVs for this gene being associated to the disorder, so this gene has been rated as RED.; Changed rating: RED
Rare multisystem ciliopathy disorders v1.100 KIAA0753 Eleanor Williams Phenotypes for gene: KIAA0753 were changed from Orofaciodigital syndrome XV 617127 to ?Orofaciodigital syndrome XV 617127; Short-rib skeletal dysplasia; Joubert syndrome
Rare multisystem ciliopathy disorders v1.99 KIAA0753 Eleanor Williams Publications for gene: KIAA0753 were set to 26643951
Rare multisystem ciliopathy disorders v1.98 KIAA0753 Eleanor Williams Classified gene: KIAA0753 as Green List (high evidence)
Rare multisystem ciliopathy disorders v1.98 KIAA0753 Eleanor Williams Added comment: Comment on list classification: 5 unrelated cases with homozygous or compound heterozygous variants in this gene and a ciliopathy-related phenotype.
Rare multisystem ciliopathy disorders v1.98 KIAA0753 Eleanor Williams Gene: kiaa0753 has been classified as Green List (High Evidence).
Dystonia, chorea or related movement disorder, adult onset v0.88 IPPK Louise Daugherty edited their review of gene: IPPK: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 HTT Louise Daugherty edited their review of gene: HTT: Added comment: This gene was uploaded from the curation template sent out to the GLHs for GMS Neurology specialist test group as it is a RED gene on the Parkinson Disease and Complex Parkinsonism panel. It relates to the STR HTT_CAG (rated GREEN) and not the gene entity, as there are no SNVs for this gene being associated to the disorder, so this gene has been rated as RED.; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 HPRT1 Louise Daugherty Deleted their comment
Dystonia, chorea or related movement disorder, adult onset v0.88 HPRT1 Louise Daugherty commented on gene: HPRT1: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED
Dystonia, chorea or related movement disorder, adult onset v0.88 GIGYF2 Louise Daugherty commented on gene: GIGYF2: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED
Dystonia, chorea or related movement disorder, adult onset v0.88 GAMT Louise Daugherty commented on gene: GAMT: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED
Dystonia, chorea or related movement disorder, adult onset v0.88 FOXRED1 Louise Daugherty commented on gene: FOXRED1: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED
Dystonia, chorea or related movement disorder, adult onset v0.88 FASTKD2 Louise Daugherty edited their review of gene: FASTKD2: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 ERCC6 Louise Daugherty edited their review of gene: ERCC6: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 EARS2 Louise Daugherty edited their review of gene: EARS2: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 DRD5 Louise Daugherty edited their review of gene: DRD5: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 DRD2 Louise Daugherty edited their review of gene: DRD2: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 DCAF10 Louise Daugherty edited their review of gene: DCAF10: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 BDNF Louise Daugherty edited their review of gene: BDNF: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 ATP6AP2 Louise Daugherty edited their review of gene: ATP6AP2: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 HPRT1 Louise Daugherty edited their review of gene: HPRT1: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 HEXA Louise Daugherty edited their review of gene: HEXA: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 GIGYF2 Louise Daugherty edited their review of gene: GIGYF2: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 GAMT Louise Daugherty edited their review of gene: GAMT: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.88 FOXRED1 Louise Daugherty edited their review of gene: FOXRED1: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Rare multisystem ciliopathy disorders v1.97 KIAA0753 Eleanor Williams commented on gene: KIAA0753
Primary lymphoedema v1.42 PIEZO1 Sarah Leigh Phenotypes for gene: PIEZO1 were changed from Lymphedema, hereditary, III 616843; Generalised lymphatic dysplasia to Lymphedema, hereditary, III 616843; Generalised lymphatic dysplasia
Primary lymphoedema v1.41 KIF11 Sarah Leigh Phenotypes for gene: KIF11 were changed from Microcephaly with or without chorioretinopathy, lymphedema, or mental retardation, 152950 to Microcephaly with or without chorioretinopathy, lymphedema, or mental retardation, MCLMR 152950
Primary lymphoedema v1.40 GJA1 Sarah Leigh Phenotypes for gene: GJA1 were changed from Oculodentodigital dysplasia with primary lymphoedem 164200 to Oculodentodigital dysplasia 164200
Primary lymphoedema v1.39 GATA2 Sarah Leigh Added comment: Comment on phenotypes: Emberger syndrome (Primary Lymphedema with Myelodysplasia) 614038
Primary lymphoedema v1.39 GATA2 Sarah Leigh Phenotypes for gene: GATA2 were changed from Primary Lymphedema with Myelodysplasia (Emberger Syndrome) 614038 to Emberger Syndrome 614038; {Myelodysplastic syndrome, susceptibility to} 614286
Dystonia, chorea or related movement disorder, adult onset v0.88 EARS2 Louise Daugherty Phenotypes for gene: EARS2 were changed from Combined oxidative phosphorylation deficiency 12, 614924.; Dystonia to Combined oxidative phosphorylation deficiency 12, 614924; Dystonia
Dystonia, chorea or related movement disorder, adult onset v0.87 C9orf72 Louise Daugherty edited their review of gene: C9orf72: Added comment: This gene was uploaded from the curation template sent out to the GLHs for GMS Neurology specialist test group as it is a RED gene on the Parkinson Disease and Complex Parkinsonism panel. It relates to the STR C9orf72_GGGGCC (rated GREEN) and not the gene entity, as there are no SNVs for this gene being associated to the disorder, so this gene has been rated as RED; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.87 ATXN3 Louise Daugherty edited their review of gene: ATXN3: Added comment: This gene was uploaded from the curation template sent out to the GLHs for GMS Neurology specialist test group as it is a RED gene on the Parkinson Disease and Complex Parkinsonism panel. It relates to the STR ATXN3_CAG (rated GREEN) and not the gene entity, as there are no SNVs for this gene being associated to the disorder, so this gene has been rated as RED.; Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.87 ATXN2 Louise Daugherty edited their review of gene: ATXN2: Added comment: This gene was uploaded from the curation template sent out to the GLHs for GMS Neurology specialist test group as it is a RED gene on the Parkinson Disease and Complex Parkinsonism panel. It relates to the STR ATXN2_CAG and not the gene entity, as there are no SNVs for this gene being associated to the disorder, this gene is rated RED.; Changed rating: RED
Structural eye disease v0.76 FAT1 Nicola Ragge reviewed gene: FAT1: Rating: GREEN; Mode of pathogenicity: ; Publications: 30862798, 12724416 ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 SMAD4 Nicola Ragge reviewed gene: SMAD4: Rating: AMBER; Mode of pathogenicity: ; Publications: 20735985, 11977156; Phenotypes: Myhre syndrome, 139210; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 PRR12 Nicola Ragge reviewed gene: PRR12: Rating: GREEN; Mode of pathogenicity: ; Publications: 29556724; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 POMT2 Nicola Ragge reviewed gene: POMT2: Rating: AMBER; Mode of pathogenicity: ; Publications: 15894594, 28815891; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 2; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 POMT1 Nicola Ragge reviewed gene: POMT1: Rating: GREEN; Mode of pathogenicity: ; Publications: 12369018, 15037715; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1, 236670; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 OLFM2 Nicola Ragge reviewed gene: OLFM2: Rating: AMBER; Mode of pathogenicity: ; Publications: 27844144; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 MITF Nicola Ragge reviewed gene: MITF: Rating: GREEN; Mode of pathogenicity: ; Publications: 27889061; Phenotypes: COMMAD syndrome, 617306; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 KIAA1109 Nicola Ragge reviewed gene: KIAA1109: Rating: GREEN; Mode of pathogenicity: ; Publications: 29290337, 617822; Phenotypes: Alkuraya-Kucinskas syndrome, ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ISPD Nicola Ragge reviewed gene: ISPD: Rating: GREEN; Mode of pathogenicity: ; Publications: 22522421; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7, 614643; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 IPO13 Nicola Ragge reviewed gene: IPO13: Rating: AMBER; Mode of pathogenicity: ; Publications: 29700284; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 GLI2 Nicola Ragge reviewed gene: GLI2: Rating: AMBER; Mode of pathogenicity: ; Publications: 17096318, 21204792; Phenotypes: Holoprosencephaly 9, 610829; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 FKRP Nicola Ragge reviewed gene: FKRP: Rating: GREEN; Mode of pathogenicity: ; Publications: 20236121, 15121789, 19955119, 20675713 ; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 5; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 EFTUD2 Nicola Ragge reviewed gene: EFTUD2: Rating: AMBER; Mode of pathogenicity: ; Publications: 26118977; Phenotypes: Mandibulofacial dysostosis, Guion-Almeida type, 610536; Mode of inheritance: mONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 CPAMD8 Nicola Ragge reviewed gene: CPAMD8: Rating: GREEN; Mode of pathogenicity: ; Publications: 27839872; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ZIC2 Nicola Ragge reviewed gene: ZIC2: Rating: AMBER; Mode of pathogenicity: ; Publications: 21976454; Phenotypes: Holoprosencephaly 5, 609637; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 ZEB2 Nicola Ragge reviewed gene: ZEB2: Rating: GREEN; Mode of pathogenicity: ; Publications: 16053902; Phenotypes: Mowat-Wilson syndrome (Hirschsprung disease with bilateral iris and retinal coloboma and high myopia), 235730; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 ZEB1 Nicola Ragge reviewed gene: ZEB1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Corneal dystrophy, posterior polymorphous, 3, Corneal dystrophy, Fuchs endothelial, 6, 609141, 613270; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 WRN Nicola Ragge reviewed gene: WRN: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Werner syndrome , 277700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 VSX1 Nicola Ragge reviewed gene: VSX1: Rating: AMBER; Mode of pathogenicity: ; Publications: 15051220; Phenotypes: Corneal dystrophy, posterior polymorphous, 1, Keratoconus 1, Craniofacial anomalies and anterior segment dysgenesis syndrome, 122000, 148300, 614195; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 VIM Nicola Ragge reviewed gene: VIM: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cataract 30, pulverulent, 116300; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 UBIAD1 Nicola Ragge reviewed gene: UBIAD1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Corneal dystrophy, Schnyder type, 121800; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 TMX3 Nicola Ragge reviewed gene: TMX3: Rating: AMBER; Mode of pathogenicity: ; Publications: Chao et al 2010 PMID: 20485507; Phenotypes: Microphthalmia, coloboma, micrognathia, diaphragmatic hernia , None; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 TGFBI Nicola Ragge reviewed gene: TGFBI: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Corneal dystrophy, epithelial basement membrane, Corneal dystrophy, Groenouw type I, Corneal dystrophy, lattice type I, Corneal dystrophy, Thiel-Behnke type, Corneal dystrophy, Avellino type, Corneal dystrophy, Reis-Bucklers type, Corneal dystrophy, lattice type IIIA, 121820, 121900, 122200, 602082, 607541, 608470, 608471; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 TDRD7 Nicola Ragge reviewed gene: TDRD7: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cataract 36, 613887; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 TCOF1 Nicola Ragge reviewed gene: TCOF1: Rating: AMBER; Mode of pathogenicity: ; Publications: 8741923, 10888597; Phenotypes: Treacher Collins syndrome 1 (eyelid coloboma), 154500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 TBX22 Nicola Ragge reviewed gene: TBX22: Rating: RED; Mode of pathogenicity: ; Publications: 22784330; Phenotypes: ?Abruzzo-Erickson syndrome, 302905; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Structural eye disease v0.76 TBC1D32 Nicola Ragge reviewed gene: TBC1D32: Rating: AMBER; Mode of pathogenicity: ; Publications: PMID: 24285566; Phenotypes: Orofaciodigital syndrome 9, 258865; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 TACSTD2 Nicola Ragge reviewed gene: TACSTD2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Corneal dystrophy, gelatinous drop-like, 204870; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 SRD5A3 Nicola Ragge reviewed gene: SRD5A3: Rating: GREEN; Mode of pathogenicity: ; Publications: PubMed: 20637498, 20700148, 26219881; Phenotypes: Kahrizi Syndrome (mental retardation, cataract, coloboma, kyphosis), 612713; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 SMCHD1 Nicola Ragge reviewed gene: SMCHD1: Rating: GREEN; Mode of pathogenicity: ; Publications: PMID: 28067909, 28067911; Phenotypes: ARHINIA, CHOANAL ATRESIA, AND MICROPHTHALMIA, 603457; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 SLC4A4 Nicola Ragge reviewed gene: SLC4A4: Rating: GREEN; Mode of pathogenicity: ; Publications: 10545938, 11274232; Phenotypes: Renal tubular acidosis, proximal, with ocular abnormalities, 604278; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 SLC4A11 Nicola Ragge reviewed gene: SLC4A11: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Corneal endothelial dystrophy and perceptive deafness, Corneal endothelial dystrophy 2, autosomal recessive, Corneal dystrophy, Fuchs endothelial, 4, 217400, 217700, 613268; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 SLC38A8 Nicola Ragge reviewed gene: SLC38A8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Foveal hypoplasia 2, with or without optic nerve misrouting and/or anterior segment dysgenesis, 609218; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 SLC33A1 Nicola Ragge reviewed gene: SLC33A1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Congenital cataracts, hearing loss, and neurodegeneration, 614482; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 SLC2A1 Nicola Ragge reviewed gene: SLC2A1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: STOMATIN-DEFICIENT CRYOHYDROCYTOSIS WITH NEUROLOGIC DEFECTS, 608885; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 SLC16A12 Nicola Ragge reviewed gene: SLC16A12: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: Cataract, juvenile, with microcornea and glucosuria, 612018; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 SIL1 Nicola Ragge reviewed gene: SIL1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Marinesco-Sjogren syndrome, 248800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 SH3PXD2B Nicola Ragge reviewed gene: SH3PXD2B: Rating: GREEN; Mode of pathogenicity: ; Publications: PMID: 20137777, 29100834 ; Phenotypes: Frank-ter Haar syndrome, 249420; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 SEMA3E Nicola Ragge reviewed gene: SEMA3E: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: CHARGE, 214800; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 SEC23A Nicola Ragge reviewed gene: SEC23A: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Craniolenticulosutural dysplasia, 607812; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 SCLT1 Nicola Ragge reviewed gene: SCLT1: Rating: GREEN; Mode of pathogenicity: ; Publications: PubMed:24285566, 29450879; Phenotypes: Orofaciodigital syndrome IX (a severe ciliopathy phenotype featuring midline cleft, microcephaly, and colobomatous microphthalmia/anophthalmia, one case only (Adly et al 2014), variant was classified as unknown significance by OMIM), None; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 SC5D Nicola Ragge reviewed gene: SC5D: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: LATHOSTEROLOSIS, 607330; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 SALL1 Nicola Ragge reviewed gene: SALL1: Rating: GREEN; Mode of pathogenicity: ; Publications: PMID: 9973281, PMID: 16088922, PMID: 17221874; Phenotypes: Townes-Brocks branchiootorenal-like syndrome, 107480; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 PXDN Nicola Ragge reviewed gene: PXDN: Rating: GREEN; Mode of pathogenicity: ; Publications: PMID: 24939590, 21907015, 29450879; Phenotypes: Corneal opacification and other ocular anomalies, 269400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PTCH1 Nicola Ragge reviewed gene: PTCH1: Rating: GREEN; Mode of pathogenicity: ; Publications: PMID: 16024850, 17001668; Phenotypes: Holoprosencephaly 7 (can include microphthalmia), 610828; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 PRDM5 Nicola Ragge reviewed gene: PRDM5: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Brittle cornea syndrome 2, 614170; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PQBP1 Nicola Ragge reviewed gene: PQBP1: Rating: AMBER; Mode of pathogenicity: ; Publications: PMID: 17033686; Phenotypes: Renpenning syndrome (can include microphthalmia/coloboma), 309500; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Structural eye disease v0.76 POLR1D Nicola Ragge reviewed gene: POLR1D: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Treacher-Collins Syndrome 2, 613717; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 POLR1C Nicola Ragge reviewed gene: POLR1C: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Treacher-Collins Syndrome, 248390; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PIKFYVE Nicola Ragge reviewed gene: PIKFYVE: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Corneal fleck dystrophy, 121850; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 PEX6 Nicola Ragge reviewed gene: PEX6: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Peroxisome biogenesis disorder 4B, 614863; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 PEX5 Nicola Ragge reviewed gene: PEX5: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Peroxisome biogenesis disorder 2B, 202370; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PEX3 Nicola Ragge reviewed gene: PEX3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Peroxisome biogenesis disorder 10A (Zellweger), 603164; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PEX26 Nicola Ragge reviewed gene: PEX26: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Peroxisome biogenesis disorder 7B, 614873; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PEX2 Nicola Ragge reviewed gene: PEX2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Peroxisome biogenesis disorder 5A (Zellweger), Peroxisome biogenesis disorder 5B, 614866, 614867; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PEX19 Nicola Ragge reviewed gene: PEX19: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Peroxisome biogenesis disorder 12A (Zellweger), 614886; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PEX16 Nicola Ragge reviewed gene: PEX16: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Peroxisome biogenesis disorder 8B, 614877; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PEX14 Nicola Ragge reviewed gene: PEX14: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Peroxisome biogenesis disorder 13A (Zellweger), 614887; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PEX13 Nicola Ragge reviewed gene: PEX13: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Peroxisome biogenesis disorder 11B, 614885; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PEX12 Nicola Ragge reviewed gene: PEX12: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Peroxisome biogenesis disorder 3B, 266510; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PEX11B Nicola Ragge reviewed gene: PEX11B: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Peroxisome biogenesis disorder 14B, 614920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PEX10 Nicola Ragge reviewed gene: PEX10: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Peroxisome biogenesis disorder 6B, 614871; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PDE6D Nicola Ragge reviewed gene: PDE6D: Rating: AMBER; Mode of pathogenicity: ; Publications: PMID:24166846; Phenotypes: ?Joubert syndrome 22 (microphthalmia/optic nerve coloboma, intrauterine growth retardation, facial dysmorphism, postaxial polydactyly of feet, syndactyly, polydactyly, renal hypoplasia, extinguished electroretinogram), 615665; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PAX3 Nicola Ragge reviewed gene: PAX3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Waardenburg syndrome, type 3, Waardenburg syndrome, type 1, 148820, 193500; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 P3H2 Nicola Ragge reviewed gene: P3H2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: MYOPIA, HIGH, WITH CATARACT AND VITREORETINAL DEGENERATION, 614292; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 OCRL Nicola Ragge reviewed gene: OCRL: Rating: AMBER; Mode of pathogenicity: ; Publications: 19168822; Phenotypes: Lowe syndrome, 309000; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Structural eye disease v0.76 NOTCH2 Nicola Ragge reviewed gene: NOTCH2: Rating: RED; Mode of pathogenicity: ; Publications: 22173065; Phenotypes: Hajdu-Cheney syndrome, Alagille syndrome 2, 102500, 610205; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 NHS Nicola Ragge reviewed gene: NHS: Rating: GREEN; Mode of pathogenicity: ; Publications: 28922055, 23566852, 17417607 ; Phenotypes: Cataract 40, X-linked, Nance-Horan syndrome, 302200, 302350; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Structural eye disease v0.76 NF2 Nicola Ragge reviewed gene: NF2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Neurofibromatosis, Type II, 101000; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 MYH9 Nicola Ragge reviewed gene: MYH9: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Epstein Syndrome, Fechtner syndrome, 153650, 153640 ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 MIR184 Nicola Ragge reviewed gene: MIR184: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: EDICT syndrome, 614303; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 MIP Nicola Ragge reviewed gene: MIP: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cataract 15, multiple types, 615274; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 MAN2B1 Nicola Ragge reviewed gene: MAN2B1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Mannosidosis, alpha-, types I and II, 248500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 LMX1B Nicola Ragge reviewed gene: LMX1B: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Nail-patella syndrome, 161200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 LIM2 Nicola Ragge reviewed gene: LIM2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cataract 19, 615277; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 LCAT Nicola Ragge reviewed gene: LCAT: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Fish-eye disease, Norum disease, 136120, 245900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 LAMB2 Nicola Ragge reviewed gene: LAMB2: Rating: GREEN; Mode of pathogenicity: ; Publications: 30778388, 30120985, 28683731, 28188379, 27130041, 29450879; Phenotypes: Pierson syndrome, Nephrotic syndrome, type 5, with or without ocular abnormalities, 609049, 614199; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 KRT3 Nicola Ragge reviewed gene: KRT3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Meesmann corneal dystrophy, 122100; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 KRT12 Nicola Ragge reviewed gene: KRT12: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Meesmann corneal dystrophy, 122100; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 KMT2D Nicola Ragge reviewed gene: KMT2D: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Kabuki syndrome 1 (can include coloboma), 147920, add review paper; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 KERA Nicola Ragge reviewed gene: KERA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: Cornea plana congenita, recessive, 217300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 KAT6B Nicola Ragge reviewed gene: KAT6B: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: SBBYSS syndrome (blepharophimosis), 603736; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 JAM3 Nicola Ragge reviewed gene: JAM3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Hemorrhagic destruction of the brain, subependymal calcification, and cataracts, 613730; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ITPR1 Nicola Ragge reviewed gene: ITPR1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Gillespie syndrome, 206700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 ITPA Nicola Ragge reviewed gene: ITPA: Rating: RED; Mode of pathogenicity: ; Publications: 26224535; Phenotypes: Warburg Micro syndrome and Martsolf syndrome with variable cardiac manifestation, None; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 HSF4 Nicola Ragge reviewed gene: HSF4: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cataract 5, multiple types, 116800; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 GSN Nicola Ragge reviewed gene: GSN: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Amyloidosis, Finnish type, 105120; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 GNPTG Nicola Ragge reviewed gene: GNPTG: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Mucolipidosis III gamma, Retinitis Pigmentosa and skeletal abnormalities, 252605; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 GJA8 Nicola Ragge reviewed gene: GJA8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Cataract 1, multiple types, 116200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 GJA3 Nicola Ragge reviewed gene: GJA3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cataract 14, multiple types, 601885; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 GFER Nicola Ragge reviewed gene: GFER: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Myopathy, mitochondrial progressive, with congenital cataract, hearing loss, and developmental delay, 613076; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 GCNT2 Nicola Ragge reviewed gene: GCNT2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cataract 13 with adult i phenotype, 116700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 GALT Nicola Ragge reviewed gene: GALT: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Galactosemia, 230400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 GALK1 Nicola Ragge reviewed gene: GALK1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Galactokinase deficiency with cataracts, 230200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 FZD5 Nicola Ragge reviewed gene: FZD5: Rating: AMBER; Mode of pathogenicity: ; Publications: Liu et al 2016 PMID: 26908622; Phenotypes: Coloboma, None; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 FYCO1 Nicola Ragge reviewed gene: FYCO1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cataract 18, autosomal recessive, 610019; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 FTL Nicola Ragge reviewed gene: FTL: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Hyperferritinemia-cataract syndrome, 600886; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 FOXL2 Nicola Ragge reviewed gene: FOXL2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Blepharophimosis, epicanthus inversus, and ptosis, 110100; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 FNBP4 Nicola Ragge reviewed gene: FNBP4: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Microphthalmia with Limb anomalies (Classified as variant of unknown significance on OMIM), 206920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 FBN1 Nicola Ragge reviewed gene: FBN1: Rating: GREEN; Mode of pathogenicity: ; Publications: 1301946, 8136837; Phenotypes: Ectopia lentis, familial, Marfan syndrome, MASS syndrome, Weill-Marchesani syndrome 2, dominant, Marfan lipodystrophy syndrome, 129600, 154700, 604308, 608328, 616914; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 FAM126A Nicola Ragge reviewed gene: FAM126A: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: LEUKODYSTROPHY, HYPOMYELINATING, 5 (includes congenital cataract), 610532; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 FAM111A Nicola Ragge reviewed gene: FAM111A: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Kenny-Caffey syndrome, type 2, Gracile bone dysplasia, 127000, 602361; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 FADD Nicola Ragge reviewed gene: FADD: Rating: RED; Mode of pathogenicity: ; Publications: Gregory-Evans et al, 2007 PMID: 17656375 ; Phenotypes: Iris coloboma, retinal coloboma , None; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 EYA1 Nicola Ragge reviewed gene: EYA1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Anterior segment anomalies with or without cataract, Branchiootic syndrome 1, 113650, 602588; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 EPHA2 Nicola Ragge reviewed gene: EPHA2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cataract 6, multiple types, 116600; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 EPG5 Nicola Ragge reviewed gene: EPG5: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Vici syndrome, 242840; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 DPYD Nicola Ragge reviewed gene: DPYD: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Dihydropyrimidine dehydrogenase deficiency , 274270; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 DHX38 Nicola Ragge reviewed gene: DHX38: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis Pigmentosa and Macular Coloboma, 618220; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 DHCR7 Nicola Ragge reviewed gene: DHCR7: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Smith-Lemli-Opitz syndrome, 270400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 DCN Nicola Ragge reviewed gene: DCN: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Corneal dystrophy, congenital stromal, 610048; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 CYP51A1 Nicola Ragge reviewed gene: CYP51A1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Structural eye disease v0.76 CTDP1 Nicola Ragge reviewed gene: CTDP1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Congenital cataracts, facial dysmorphism, and neuropathy, 604168; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CRYGS Nicola Ragge reviewed gene: CRYGS: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cataract 20, multiple types, 116100; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 CRYGD Nicola Ragge reviewed gene: CRYGD: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: Cataract 4, Multiple Types, 115700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 CRYGC Nicola Ragge reviewed gene: CRYGC: Rating: GREEN; Mode of pathogenicity: ; Publications: 24281366, 29386872; Phenotypes: Cataract 2, multiple types (often with microcornea), 604307; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 CRYGB Nicola Ragge reviewed gene: CRYGB: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cataract 39, multiple types, autosomal dominant, 615188; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 CRYBB3 Nicola Ragge reviewed gene: CRYBB3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cataract 22, autosomal recessive, 609741; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 CRYBB2 Nicola Ragge reviewed gene: CRYBB2: Rating: AMBER; Mode of pathogenicity: ; Publications: 29386872; Phenotypes: Cataract 3, multiple types, 601547; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 CRYBB1 Nicola Ragge reviewed gene: CRYBB1: Rating: AMBER; Mode of pathogenicity: ; Publications: 29386872; Phenotypes: Cataract 17, multiple types, 611544; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 CRYBA4 Nicola Ragge reviewed gene: CRYBA4: Rating: AMBER; Mode of pathogenicity: ; Publications: 16960806, 20577656 ; Phenotypes: Cataract 23 (and microphthalmia in 1 case), 610425; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 CRYBA1 Nicola Ragge reviewed gene: CRYBA1: Rating: RED; Mode of pathogenicity: ; Publications: 26303524; Phenotypes: Cataract 10, multiple types, 600881; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 CRYAB Nicola Ragge reviewed gene: CRYAB: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: CATARACT 16, MULTIPLE TYPES, 613763; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 CRYAA Nicola Ragge reviewed gene: CRYAA: Rating: GREEN; Mode of pathogenicity: ; Publications: 17296897, 30340470 , 18302245 ; Phenotypes: Cataract 9, multiple types (some patients also have microphthalmia and/or microcornea), 604219; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 CRIM1 Nicola Ragge reviewed gene: CRIM1: Rating: AMBER; Mode of pathogenicity: ; Publications: 26681494, 25561690; Phenotypes: Macrophthalmia, Colobomatous, with microcornea, 602499; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 COL8A2 Nicola Ragge reviewed gene: COL8A2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Corneal dystrophy, Fuchs endothelial, 1, Corneal dystrophy, posterior polymorphous 2, 136800, 609140; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 COL18A1 Nicola Ragge reviewed gene: COL18A1: Rating: GREEN; Mode of pathogenicity: ; Publications: 17546652, 22399687; Phenotypes: Knobloch syndrome, type 1, 267750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CHST6 Nicola Ragge reviewed gene: CHST6: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Macular corneal dystrophy, 217800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CHRDL1 Nicola Ragge reviewed gene: CHRDL1: Rating: GREEN; Mode of pathogenicity: ; Publications: 22284829; Phenotypes: Megalocornea 1, X-linked, 309300; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Structural eye disease v0.76 CHMP4B Nicola Ragge reviewed gene: CHMP4B: Rating: RED; Mode of pathogenicity: ; Publications: 17701905; Phenotypes: Cataract 31, multiple types, 605387; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 CBS Nicola Ragge reviewed gene: CBS: Rating: GREEN; Mode of pathogenicity: ; Publications: 7611293, 24169224, 21626167, 11774777; Phenotypes: Homocystinuria, B6-responsive and nonresponsive types (includes ectopia lentis), 236200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 BFSP2 Nicola Ragge reviewed gene: BFSP2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cataract 12, multiple types, 611597; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 BFSP1 Nicola Ragge reviewed gene: BFSP1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cataract 33, 611391; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 ALDH18A1 Nicola Ragge reviewed gene: ALDH18A1: Rating: RED; Mode of pathogenicity: ; Publications: 21739576; Phenotypes: Cutis laxa, autosomal recessive, type IIIA, 219150; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 AGPS Nicola Ragge reviewed gene: AGPS: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Rhizomelic chondrodysplasia punctata, type 3, 600121; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 AGK Nicola Ragge reviewed gene: AGK: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Sengers syndrome, Cataract 38, autosomal recessive, 212350, 614691; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 AGBL1 Nicola Ragge reviewed gene: AGBL1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Corneal dystrophy, Fuchs endothelial, 8, 615523; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 ADAMTSL4 Nicola Ragge reviewed gene: ADAMTSL4: Rating: GREEN; Mode of pathogenicity: ; Publications: 20702823, 20141359, 25975359 ; Phenotypes: Ectopia lentis, isolated, autosomal recessive, Ectopia lentis et pupillae, 225100, 225200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ADAMTS18 Nicola Ragge reviewed gene: ADAMTS18: Rating: GREEN; Mode of pathogenicity: ; Publications: 23818446; Phenotypes: Microcornea, myopic chorioretinal atrophy, and telecanthus, 615458; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ZNF513 Nicola Ragge reviewed gene: ZNF513: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 58, 613617; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ZNF423 Nicola Ragge reviewed gene: ZNF423: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Joubert syndrome 19, Nephronophthisis 14, 614844, 614844; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 XPC Nicola Ragge reviewed gene: XPC: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP C, 278720; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 XPA Nicola Ragge reviewed gene: XPA: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP A, 278700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 WT1 Nicola Ragge reviewed gene: WT1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: WILMS TUMOR,ANIRIDIA, GENITOURINARY ANOMALIES, AND MENTAL RETARDATION SYNDROME, 194072; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 WHRN Nicola Ragge reviewed gene: WHRN: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Usher syndrome, type 2D, 611383; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 WFS1 Nicola Ragge reviewed gene: WFS1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Wolfram syndrome, Wolfram-like syndrome, autosomal dominant, ?Cataract 41, 222300, 614296, 116400; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 WDR36 Nicola Ragge reviewed gene: WDR36: Rating: RED; Mode of pathogenicity: ; Publications: 17353431, 18172102, 15677485; Phenotypes: Glaucoma 1, open angle, G, 609887; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 WDPCP Nicola Ragge reviewed gene: WDPCP: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ?Bardet-Biedl syndrome 15, 615992; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 VCAN Nicola Ragge reviewed gene: VCAN: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Wagner syndrome 1, 143200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 VAX1 Nicola Ragge reviewed gene: VAX1: Rating: AMBER; Mode of pathogenicity: ; Publications: 10601035, 22095910; Phenotypes: Microphthalmia, syndromic 11, 614402; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 USH2A Nicola Ragge reviewed gene: USH2A: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 39, Usher syndrome type 2A, 613809, 276901; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 USH1G Nicola Ragge reviewed gene: USH1G: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Usher syndrome, type 1G, 606943; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 USH1C Nicola Ragge reviewed gene: USH1C: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Deafness, autosomal recessive 18A, Usher syndrome type 1C, 602092, 276904; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 UNC119 Nicola Ragge reviewed gene: UNC119: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cone-rod dystrophy, Immunodeficiency 13, , 615518; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 TYRP1 Nicola Ragge reviewed gene: TYRP1: Rating: RED; Mode of pathogenicity: ; Publications: 10644000; Phenotypes: Albinism, oculocutaneous, type III, [Skin/hair/eye pigmentation, variation in, 11 (Melanesian blond hair)], 203290, 612271; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 TYR Nicola Ragge reviewed gene: TYR: Rating: RED; Mode of pathogenicity: ; Publications: 28778995; Phenotypes: Albinism, oculocutaneous, type IA, Albinism, oculocutaneous, type IB, Waardenburg syndrome/albinism, digenic, [Skin/hair/eye pigmentation 3, blue/green eyes], [Skin/hair/eye pigmentation 3, light/dark/freckling skin], {Melanoma, cutaneous malignant, susceptibility to, 8}, 203100, 606952, 103470, 601800, 601800, 601800; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 TULP1 Nicola Ragge reviewed gene: TULP1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Leber congenital amaurosis 15, Retinitis pigmentosa 14, 613843, 600132; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 TTC8 Nicola Ragge reviewed gene: TTC8: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 51, Bardet-Biedl syndrome 8, 613464, 615985; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 TTC21B Nicola Ragge reviewed gene: TTC21B: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: SHORT-RIB THORACIC DYSPLASIA 4 WITH OR WITHOUT POLYDACTYLY, 613819; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 TSPAN12 Nicola Ragge reviewed gene: TSPAN12: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Exudative vitreoretinopathy 5, 613310; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 TRPM1 Nicola Ragge reviewed gene: TRPM1: Rating: RED; Mode of pathogenicity: other - please provide details in the comments; Publications: ; Phenotypes: Night blindness, congenital stationary (complete), 1C, autosomal recessive, 613216; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 TRIM44 Nicola Ragge reviewed gene: TRIM44: Rating: RED; Mode of pathogenicity: ; Publications: 26394807; Phenotypes: ANIRIDIA 3, 617142; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 TRIM32 Nicola Ragge reviewed gene: TRIM32: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Bardet-Biedl syndrome 11, Muscular dystrophy, limb-girdle, type 2H, 615988, 254110; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 TPP1 Nicola Ragge reviewed gene: TPP1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: CEROID LIPOFUSCINOSIS, NEURONAL, 2, 204500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 TP53BP2 Nicola Ragge reviewed gene: TP53BP2: Rating: RED; Mode of pathogenicity: ; Publications: 28150229, 27447114, ; Phenotypes: ; Mode of inheritance:
Structural eye disease v0.76 TOPORS Nicola Ragge reviewed gene: TOPORS: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 31, 609923; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 TMEM67 Nicola Ragge reviewed gene: TMEM67: Rating: GREEN; Mode of pathogenicity: ; Publications: 19058225, 30055837 ; Phenotypes: COACH syndrome, Joubert syndrome 6, Meckel syndrome 3, Nephronophthisis 11, {Bardet-Biedl syndrome 14, modifer of}, 216360, 610688, 607361, 613550, 615991; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 TMEM237 Nicola Ragge reviewed gene: TMEM237: Rating: GREEN; Mode of pathogenicity: ; Publications: 22152675, 30055837 ; Phenotypes: Joubert syndrome 14, 614424; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 TMEM231 Nicola Ragge reviewed gene: TMEM231: Rating: RED; Mode of pathogenicity: ; Publications: 23012439, 23349226; Phenotypes: Joubert syndrome 20, Meckel syndrome 11, 614970, 615397; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 TMEM216 Nicola Ragge reviewed gene: TMEM216: Rating: GREEN; Mode of pathogenicity: ; Publications: 20512146, 30055837; Phenotypes: Joubert syndrome 2, Meckel syndrome 2, 608091, 603194; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 TMEM138 Nicola Ragge reviewed gene: TMEM138: Rating: RED; Mode of pathogenicity: ; Publications: 22282472; Phenotypes: Joubert syndrome 16, 614465; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 TMEM126A Nicola Ragge reviewed gene: TMEM126A: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Optic atrophy, 612989; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 TIMP3 Nicola Ragge reviewed gene: TIMP3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Sorsby fundus dystrophy, 136900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 TIMM8A Nicola Ragge reviewed gene: TIMM8A: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Mohr-Tranebjaerg syndrome, 304700; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Structural eye disease v0.76 TFAP2A Nicola Ragge reviewed gene: TFAP2A: Rating: GREEN; Mode of pathogenicity: ; Publications: 18423521, 19685247 ; Phenotypes: Branchiooculofacial syndrome (includes ocular anomalies such as microphthalmia and lacrimal duct obstruction), 113620; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 TENM3 Nicola Ragge reviewed gene: TENM3: Rating: GREEN; Mode of pathogenicity: ; Publications: 22766609, 27103084, 24859618, 29753094, 30513139; Phenotypes: Microphthalmia, isolated, with coloboma 9, 615145; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 TCTN3 Nicola Ragge reviewed gene: TCTN3: Rating: RED; Mode of pathogenicity: ; Publications: 25118024, 29725084; Phenotypes: Joubert syndrome 18, Orofaciodigital syndrome IV, 614815, 258860; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 TCTN2 Nicola Ragge reviewed gene: TCTN2: Rating: RED; Mode of pathogenicity: ; Publications: 21565611, 25118024; Phenotypes: Meckel syndrome 8, Joubert syndrome 24, 613885, 616654; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 TCTN1 Nicola Ragge reviewed gene: TCTN1: Rating: RED; Mode of pathogenicity: ; Publications: 21725307, 22693042; Phenotypes: Joubert syndrome 13, 614173; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 SPINT2 Nicola Ragge reviewed gene: SPINT2: Rating: RED; Mode of pathogenicity: ; Publications: 29575628, 24142340, ; Phenotypes: DIARRHEA 3, SECRETORY SODIUM, CONGENITAL, WITH OR WITHOUT OTHER CONGENITAL ANOMALIES, 270420; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 SPATA7 Nicola Ragge reviewed gene: SPATA7: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Leber congenital amaurosis 3, Retinitis pigmentosa, juvenile, autosomal recessive, 604232, 604232; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 SNRNP200 Nicola Ragge reviewed gene: SNRNP200: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 33, 610359; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 SLC45A2 Nicola Ragge reviewed gene: SLC45A2: Rating: RED; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Albinism, oculocutaneous, type IV, [Skin/hair/eye pigmentation 5, black/nonblack hair], [Skin/hair/eye pigmentation 5, dark/fair skin], [Skin/hair/eye pigmentation 5, dark/light eyes] , 606574, 227240, 227240, 227240; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 SLC24A5 Nicola Ragge reviewed gene: SLC24A5: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ALBINISM, OCULOCUTANEOUS, TYPE VI, 113750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 SLC24A1 Nicola Ragge reviewed gene: SLC24A1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Night blindness, congenital stationary (complete), 1D, autosomal recessive, 613830; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 SIX3 Nicola Ragge reviewed gene: SIX3: Rating: AMBER; Mode of pathogenicity: ; Publications: 21976454, 10369266, 21940735; Phenotypes: Holoprosencephaly 2, , 157170; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 SEMA4A Nicola Ragge reviewed gene: SEMA4A: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 35, Cone-rod dystrophy 10, 610282, 610283; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 SDCCAG8 Nicola Ragge reviewed gene: SDCCAG8: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Senior-Loken syndrome 7, Bardet-Biedl syndrome 16, 613615, 615993; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 SALL2 Nicola Ragge reviewed gene: SALL2: Rating: AMBER; Mode of pathogenicity: Other - please provide details in the comments; Publications: 24412933; Phenotypes: Coloboma, ocular, autosomal recessive, 216820; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 SAG Nicola Ragge reviewed gene: SAG: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Oguchi disease-1, Retinitis pigmentosa 47, 258100, 613758; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 RS1 Nicola Ragge reviewed gene: RS1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinoschisis, 312700; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Structural eye disease v0.76 RPGRIP1 Nicola Ragge reviewed gene: RPGRIP1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cone-rod dystrophy 13, Leber congenital amaurosis 6, 608194, 613826; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 RPGR Nicola Ragge reviewed gene: RPGR: Rating: RED; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Retinitis pigmentosa 3, Retinitis pigmentosa, X-linked, and sinorespiratory infections, with or without deafness, Macular degeneration, X-linked atrophic, Cone-rod dystrophy, X-linked, 1 , 300029, 300455, 300834, 304020; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Structural eye disease v0.76 RPE65 Nicola Ragge reviewed gene: RPE65: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Leber congenital amaurosis 2, 204100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 RP9 Nicola Ragge reviewed gene: RP9: Rating: RED; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: ?Retinitis pigmentosa 9, 180104; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 RP2 Nicola Ragge reviewed gene: RP2: Rating: RED; Mode of pathogenicity: ; Publications: 21738648; Phenotypes: Retinitis pigmentosa 2, 312600; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Structural eye disease v0.76 RP1 Nicola Ragge reviewed gene: RP1: Rating: RED; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Retinitis pigmentosa 1, 180100; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 ROM1 Nicola Ragge reviewed gene: ROM1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 7, digenic, 608133; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 RLBP1 Nicola Ragge reviewed gene: RLBP1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Bothnia retinal dystrophy, Newfoundland rod-cone dystrophy, Fundus albipunctatus, 607475, 607476, 136880; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 RIMS1 Nicola Ragge reviewed gene: RIMS1: Rating: RED; Mode of pathogenicity: Other - please provide details in the comments; Publications: 28677725; Phenotypes: Cone-rod dystrophy 7, 603649; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 RHO Nicola Ragge reviewed gene: RHO: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 4, autosomal dominant or recessive, Night blindness, congenital stationary, autosomal dominant 1, , 613731, 610445, 136880; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 RGS9BP Nicola Ragge reviewed gene: RGS9BP: Rating: RED; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Bradyopsia, 608415; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 RGS9 Nicola Ragge reviewed gene: RGS9: Rating: RED; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Bradyopsia, 608415; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 RGR Nicola Ragge reviewed gene: RGR: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 44, 613769; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 RDH5 Nicola Ragge reviewed gene: RDH5: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Fundus albipunctatus, 136880; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 RDH12 Nicola Ragge reviewed gene: RDH12: Rating: RED; Mode of pathogenicity: ; Publications: 25148430, 22065924; Phenotypes: Leber congenital amaurosis 13, 612712; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 RD3 Nicola Ragge reviewed gene: RD3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Leber congenital amaurosis 12, 610612; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 RBP3 Nicola Ragge reviewed gene: RBP3: Rating: RED; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: ?Retinitis pigmentosa 66, 615233; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 RAX2 Nicola Ragge reviewed gene: RAX2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cone-rod dystrophy 11, Macular degeneration, age-related, 6, 610381, 613757; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 PRPH2 Nicola Ragge reviewed gene: PRPH2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis punctata albescens, Macular dystrophy, patterned, 1, Leber congenital amaurosis 18, Macular dystrophy, vitelliform, 3, Choriodal dystrophy, central areolar 2 , 136880, 169150, 608133, 608161, 613105; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 PRPF8 Nicola Ragge reviewed gene: PRPF8: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 13, 600059; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 PRPF6 Nicola Ragge reviewed gene: PRPF6: Rating: RED; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Retinitis pigmentosa 60, 613983; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 PRPF31 Nicola Ragge reviewed gene: PRPF31: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 11, 600138; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 PRPF3 Nicola Ragge reviewed gene: PRPF3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 18, 601414; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 PROM1 Nicola Ragge reviewed gene: PROM1: Rating: RED; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Stargardt disease 4, Macular dystrophy, retinal, 2, Retinitis pigmentosa 41, Cone-rod dystrophy 12, 603786, 608051, 612095, 612657; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 PRCD Nicola Ragge reviewed gene: PRCD: Rating: RED; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Retinitis pigmentosa 36, 610599; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PPT1 Nicola Ragge reviewed gene: PPT1: Rating: RED; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: CEROID LIPOFUSCINOSIS, NEURONAL, 1, 256730; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 POLH Nicola Ragge reviewed gene: POLH: Rating: RED; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: XERODERMA PIGMENTOSUM, VARIANT TYPE, 278750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PLA2G5 Nicola Ragge reviewed gene: PLA2G5: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: [Fleck retina, familial benign], 228980; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PITX3 Nicola Ragge reviewed gene: PITX3: Rating: GREEN; Mode of pathogenicity: ; Publications: 20033184, 29405783, 9620774; Phenotypes: Anterior segment mesenchymal dysgenesis, Cataract 11, multiple types, 107250, 610623; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 PITPNM3 Nicola Ragge reviewed gene: PITPNM3: Rating: RED; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Cone-rod dystrophy 5, 600977; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 PHYH Nicola Ragge reviewed gene: PHYH: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Refsum disease, 266500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PEX7 Nicola Ragge reviewed gene: PEX7: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Rhizomelic chondrodysplasia punctata, type 1, Peroxisome biogenesis disorder 9B, 215100, 614879; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PDZD7 Nicola Ragge reviewed gene: PDZD7: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Usher syndrome, type IIC, GPR98/PDZD7 digenic, Retinal disease in Usher syndrome type IIA, modifier of, 605472, 276901; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PDE6H Nicola Ragge reviewed gene: PDE6H: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Achromatopsia 6, 610024; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 PDE6G Nicola Ragge reviewed gene: PDE6G: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 57, 613582; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PDE6C Nicola Ragge reviewed gene: PDE6C: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cone dystrophy 4, 613093; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PDE6B Nicola Ragge reviewed gene: PDE6B: Rating: RED; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Night blindness, congenital stationary, autosomal dominant 2, Retinitis pigmentosa-40, 163500, 613801; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 PDE6A Nicola Ragge reviewed gene: PDE6A: Rating: RED; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Retinitis pigmentosa 43, 613810; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PCDH15 Nicola Ragge reviewed gene: PCDH15: Rating: RED; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Usher syndrome, type 1D/F digenic, Usher syndrome, type 1F, Deafness, autosomal recessive 23, 601067, 602083, 609533; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 OPTN Nicola Ragge reviewed gene: OPTN: Rating: RED; Mode of pathogenicity: ; Publications: 11834836; Phenotypes: Glaucoma 1, open angle, E, 137760; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 OPA3 Nicola Ragge reviewed gene: OPA3: Rating: RED; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Optic atrophy 3 with cataract, 165300; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 OPA1 Nicola Ragge reviewed gene: OPA1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Optic atrophy plus syndrome, Optic atrophy 1, Behr syndrome, Glaucoma, normal tension, susceptibility to, , 125250, 165500, 210000, ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 OFD1 Nicola Ragge reviewed gene: OFD1: Rating: AMBER; Mode of pathogenicity: Other - please provide details in the comments; Publications: 28173652; Phenotypes: Joubert syndrome 10, ?Retinitis pigmentosa 23, 300804, 300424; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Structural eye disease v0.76 OCA2 Nicola Ragge reviewed gene: OCA2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Albinism, brown oculocutaneous, Albinism oculocutaneous, type II, [Skin/hair/eye pigmentation 1, blond/brown hair], [Skin/hair/eye pigmentation 1, blue/nonblue eyes], 203200, 203200, 227220, 227220; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 OAT Nicola Ragge reviewed gene: OAT: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Gyrate atrophy of choroid and retina with or without ornithinemia, 258870; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 NYX Nicola Ragge reviewed gene: NYX: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Night blindness, congenital stationary (complete), 1A, X-linked, 310500; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Structural eye disease v0.76 NTF4 Nicola Ragge reviewed gene: NTF4: Rating: RED; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: GLAUCOMA 1, OPEN ANGLE, O, 613100; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 NRL Nicola Ragge reviewed gene: NRL: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 27, 613750; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 NR2E3 Nicola Ragge reviewed gene: NR2E3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 37, Enhanced S-cone syndrome, 611131, 268100; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 NPHP4 Nicola Ragge reviewed gene: NPHP4: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Nephronophthisis 4, Senior-Loken syndrome 4, 606966, 606996; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 NPHP3 Nicola Ragge reviewed gene: NPHP3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Nephronophthisis 3, Meckel syndrome 7, Renal-hepatic-pancreatic dysplasia 1, 604387, 267010, 208540; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 NPHP1 Nicola Ragge reviewed gene: NPHP1: Rating: RED; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Nephronophthisis 1, juvenile, Senior-Loken syndrome-1, Joubert syndrome 4, 256100, 266900, 609583; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 NDP Nicola Ragge reviewed gene: NDP: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: 26130484, 29617172, 29321361, 17334993; Phenotypes: Exudative vitreoretinopathy 2, X-linked, Norrie disease, 305390, 310600; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Structural eye disease v0.76 NAA10 Nicola Ragge reviewed gene: NAA10: Rating: GREEN; Mode of pathogenicity: other - please provide details in the comments; Publications: 24431331, 30842225; Phenotypes: Microphthalmia, syndromic 1, 309800; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Structural eye disease v0.76 MYO7A Nicola Ragge reviewed gene: MYO7A: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Usher syndrome, type 1B, Deafness, autosomal recessive 2, Deafness, autosomal dominant 11, 276900, 601317; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 MTTP Nicola Ragge reviewed gene: MTTP: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Abetalipoproteinemia, 200100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 MPLKIP Nicola Ragge reviewed gene: MPLKIP: Rating: RED; Mode of pathogenicity: ; Publications: 21959366; Phenotypes: TRICHOTHIODYSTROPHY 4, NONPHOTOSENSITIVE, 234050; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 MKS1 Nicola Ragge reviewed gene: MKS1: Rating: RED; Mode of pathogenicity: ; Publications: 23454480; Phenotypes: Bardet-Biedl syndrome 13, Meckel syndrome 1, 615990, 249000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 MKKS Nicola Ragge reviewed gene: MKKS: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Bardet-Biedl syndrome 6, McKusick-Kaufman syndrome, 605231, 236700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 MIR204 Nicola Ragge reviewed gene: MIR204: Rating: AMBER; Mode of pathogenicity: ; Publications: 26056285; Phenotypes: RETINAL DYSTROPHY AND IRIS COLOBOMA WITH OR WITHOUT CONGENITAL CATARACT, 616722; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 MFSD8 Nicola Ragge reviewed gene: MFSD8: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: CEROID LIPOFUSCINOSIS, NEURONAL, 7, MACULAR DYSTROPHY WITH CENTRAL CONE INVOLVEMENT, 610951, 616170; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 MFN2 Nicola Ragge reviewed gene: MFN2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Charcot-Marie-Tooth disease, type 2A2, 609260; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 MERTK Nicola Ragge reviewed gene: MERTK: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 38, 613862; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 MAK Nicola Ragge reviewed gene: MAK: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 62, 614181; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 LZTFL1 Nicola Ragge reviewed gene: LZTFL1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Bardet-Biedl syndrome 17, 615994; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 LRP5 Nicola Ragge reviewed gene: LRP5: Rating: GREEN; Mode of pathogenicity: ; Publications: 29131652, 28111184, 20034086; Phenotypes: Osteoporosis-pseudoglioma syndrome, Exudative vitreoretinopathy 4, Osteopetrosis, autosomal dominant 1, van Buchem disease, type 2, 259770, 601813, 607634, ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 LRMDA Nicola Ragge reviewed gene: LRMDA: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ALBINISM, OCULOCUTANEOUS, TYPE VII, 615179; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 LRIT3 Nicola Ragge reviewed gene: LRIT3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Night blindness, congenital stationary (complete), 1F, autosomal recessive, 615058; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 LRAT Nicola Ragge reviewed gene: LRAT: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Leber congenital amaurosis 14, 613341; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 LCA5 Nicola Ragge reviewed gene: LCA5: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Leber congenital amaurosis 5, 604537; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 KLHL7 Nicola Ragge reviewed gene: KLHL7: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 42, 612943; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 KIF7 Nicola Ragge reviewed gene: KIF7: Rating: RED; Mode of pathogenicity: ; Publications: 21633164; Phenotypes: Acrocallosal syndrom (JOUBERT SYNDROME 12), 200990; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 KCTD7 Nicola Ragge reviewed gene: KCTD7: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: EPILEPSY, PROGRESSIVE MYOCLONIC, 3, WITH OR WITHOUT INTRACELLULAR INCLUSIONS, 611726; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 KCNV2 Nicola Ragge reviewed gene: KCNV2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinal cone dystrophy 3B, 610356; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 KCNJ13 Nicola Ragge reviewed gene: KCNJ13: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Leber congenital amaurosis 16, Snowflake vitreoretinal degeneration, 614186, 193230; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 IQCB1 Nicola Ragge reviewed gene: IQCB1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Senior-Loken syndrome 5: an autosomal recessive disorder with the main features of nephronophthisis (NPHP, see 256100) and Leber congenital amaurosis (LCA, see 204000)., 609254; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 INVS Nicola Ragge reviewed gene: INVS: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Nephronophthisis 2, infantile, 602088; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 INPP5E Nicola Ragge reviewed gene: INPP5E: Rating: GREEN; Mode of pathogenicity: ; Publications: 23386033, 30055837, 23022135; Phenotypes: Joubert syndrome 1, Mental retardation, truncal obesity, retinal dystrophy, and micropenis, 213300, 610156; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 IMPG2 Nicola Ragge reviewed gene: IMPG2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 56, Macular dystrophy, vitelliform, 5, 613581, 616152; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 IMPDH1 Nicola Ragge reviewed gene: IMPDH1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 10, Leber congenital amaurosis 11, 180105, 613837; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 IDH3B Nicola Ragge reviewed gene: IDH3B: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 46, 612572; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 HMGB3 Nicola Ragge reviewed gene: HMGB3: Rating: AMBER; Mode of pathogenicity: ; Publications: 24993872, ; Phenotypes: ?Microphthalmia, syndromic 13, 300915; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Structural eye disease v0.76 HDAC6 Nicola Ragge reviewed gene: HDAC6: Rating: RED; Mode of pathogenicity: other - please provide details in the comments; Publications: 20181727; Phenotypes: CHONDRODYSPLASIA WITH PLATYSPONDYLY, DISTINCTIVE BRACHYDACTYLY, HYDROCEPHALY, AND MICROPHTHALMIA, 300863; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Structural eye disease v0.76 HARS Nicola Ragge reviewed gene: HARS: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Usher syndrome type 3B, Charcot-Marie-Tooth disease, axonal, type 2W, 614504, 616625; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 GUCY2D Nicola Ragge reviewed gene: GUCY2D: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Leber congenital amaurosis 1, Cone-rod dystrophy 6, 204000, 601777; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 GUCA1B Nicola Ragge reviewed gene: GUCA1B: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 48, 613827; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 GUCA1A Nicola Ragge reviewed gene: GUCA1A: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cone dystrophy-3, 602093; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 GTF2H5 Nicola Ragge reviewed gene: GTF2H5: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: TRICHOTHIODYSTROPHY 3, PHOTOSENSITIVE, 616395; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 GRN Nicola Ragge reviewed gene: GRN: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: CEROID LIPOFUSCINOSIS, NEURONAL, 11, 614706; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 GRM6 Nicola Ragge reviewed gene: GRM6: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Night blindness, congenital stationary (complete), 1B, autosomal recessive, 257270; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 GPR179 Nicola Ragge reviewed gene: GPR179: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Night blindness, congenital stationary (complete), 1E, autosomal recessive, 614565; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 GPR143 Nicola Ragge reviewed gene: GPR143: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Nystagmus 6, congenital, X-linked, Ocular albinism, type I, Nettleship-Falls type, 300814, 300500; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Structural eye disease v0.76 GNAT2 Nicola Ragge reviewed gene: GNAT2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Achromatopsia-4, 613856; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 GNAT1 Nicola Ragge reviewed gene: GNAT1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Night blindness, congenital stationary, autosomal dominant 3, ?Night blindness, congenital stationary, type 1G, 610444, 616389; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 GDF6 Nicola Ragge reviewed gene: GDF6: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: 17236135, 20494911, 25457163, 24033328, 21070663; Phenotypes: KLIPPEL-FEIL SYNDROME 1(includes microphthalmia), Microphthalmia with coloboma6, digenic (with GDF3), Microphthalmia, isolated 4 , 118100 , 613703 , 613094 ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 GDF3 Nicola Ragge reviewed gene: GDF3: Rating: AMBER; Mode of pathogenicity: other - please provide details in the comments; Publications: 19864492; Phenotypes: Klippel-Feil Syndrome3, Microphthalmia with coloboma 6, Microphthalmia, isolated 7, 613702, 613703, 613704; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 FZD4 Nicola Ragge reviewed gene: FZD4: Rating: AMBER; Mode of pathogenicity: ; Publications: 28413837, 30882657; Phenotypes: Exudative vitreoretinopathy 1, 133780; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 FSCN2 Nicola Ragge reviewed gene: FSCN2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 30, 607921; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 FLVCR1 Nicola Ragge reviewed gene: FLVCR1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Ataxia, posterior column, with retinitis pigmentosa, 609033; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 FAM161A Nicola Ragge reviewed gene: FAM161A: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 28, 606068; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 EYS Nicola Ragge reviewed gene: EYS: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 25, 602772; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ERCC8 Nicola Ragge reviewed gene: ERCC8: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cockayne syndrome, type A, 216400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ERCC6 Nicola Ragge reviewed gene: ERCC6: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cerebrooculofacioskeletal syndrome 1, Macular degeneration, age-related, susceptibility to 5, 214150, 613761; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ERCC5 Nicola Ragge reviewed gene: ERCC5: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Xeroderma Pigmentosum, group G (includes microphthalmia and/or cataract), Cerebrooculofacioskeletal syndrome 3, 278780, 616570; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ERCC4 Nicola Ragge reviewed gene: ERCC4: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP F, 278760; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ERCC3 Nicola Ragge reviewed gene: ERCC3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: TRICHOTHIODYSTROPHY 2, PHOTOSENSITIVE, 616390; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ERCC2 Nicola Ragge reviewed gene: ERCC2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: TRICHOTHIODYSTROPHY 1, PHOTOSENSITIVE, 601675; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ERCC1 Nicola Ragge reviewed gene: ERCC1: Rating: AMBER; Mode of pathogenicity: ; Publications: 17273966; Phenotypes: Cerebrooculofacioskeletal syndrome 4 (includes microphthalmia), 610758; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ELP4 Nicola Ragge reviewed gene: ELP4: Rating: RED; Mode of pathogenicity: ; Publications: 24290376, 29217025; Phenotypes: ANIRIDIA 2, 617141; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 ELOVL4 Nicola Ragge reviewed gene: ELOVL4: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Stargardt disease 3, 600110; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 EFEMP1 Nicola Ragge reviewed gene: EFEMP1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Doyne honeycomb degeneration of retina, 126600; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 DHDDS Nicola Ragge reviewed gene: DHDDS: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 59, 613861; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 DDB2 Nicola Ragge reviewed gene: DDB2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP E, 278740; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 DDB1 Nicola Ragge reviewed gene: DDB1: Rating: RED; Mode of pathogenicity: ; Publications: 17129780; Phenotypes: ; Mode of inheritance:
Structural eye disease v0.76 CYP4V2 Nicola Ragge reviewed gene: CYP4V2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Bietti crystalline corneoretinal dystrophy, 210370; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CYP27A1 Nicola Ragge reviewed gene: CYP27A1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: CEREBROTENDINOUS XANTHOMATOSIS, 213700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CTSD Nicola Ragge reviewed gene: CTSD: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: CEROID LIPOFUSCINOSIS, NEURONAL, 10, 610127; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CRX Nicola Ragge reviewed gene: CRX: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cone-rod retinal dystrophy-2, Leber congenital amaurosis 7, 120970, 613829; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 CRB1 Nicola Ragge reviewed gene: CRB1: Rating: AMBER; Mode of pathogenicity: ; Publications: 21484995, 23077403; Phenotypes: Leber congenital amaurosis 8, Retinitis pigmentosa-12, autosomal recessive, Pigmented paravenous chorioretinal atrophy, 613835, 600105; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 COL9A2 Nicola Ragge reviewed gene: COL9A2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: STICKLER SYNDROME, TYPE V, 614284; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 COL9A1 Nicola Ragge reviewed gene: COL9A1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Stickler syndrome, type IV, 614134; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 COL2A1 Nicola Ragge reviewed gene: COL2A1: Rating: AMBER; Mode of pathogenicity: ; Publications: 18541977, 17347327; Phenotypes: Vitreoretinopathy with phalangeal epiphyseal dysplasia, Stickler syndrome, type I, Epiphyseal dysplasia, multiple, with myopia and deafness, Kniest dysplasia, SED congenita, Stickler sydrome, type I, nonsyndromic ocular, , , 108300, 156550, 609508; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 COL11A2 Nicola Ragge reviewed gene: COL11A2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 COL11A1 Nicola Ragge reviewed gene: COL11A1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Stickler syndrome, type II, Marshall syndrome, 604841, 154780; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 CNNM4 Nicola Ragge reviewed gene: CNNM4: Rating: AMBER; Mode of pathogenicity: ; Publications: 27419834; Phenotypes: Jalili syndrome, 217080; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CNGB3 Nicola Ragge reviewed gene: CNGB3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Macular degeneration, juvenile, Achromatopsia-3, 248200, 262300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CNGB1 Nicola Ragge reviewed gene: CNGB1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 45, 613767; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CNGA3 Nicola Ragge reviewed gene: CNGA3: Rating: RED; Mode of pathogenicity: ; Publications: 24504161; Phenotypes: Achromatopsia-2, 216900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CNGA1 Nicola Ragge reviewed gene: CNGA1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 49, 613756; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CLRN1 Nicola Ragge reviewed gene: CLRN1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Usher syndrome, type 3A, Retinitis pigmentosa 61, 276902, 614180; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CLN8 Nicola Ragge reviewed gene: CLN8: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Ceroid lipofuscinosis, neuronal, 8, 600143; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CLN6 Nicola Ragge reviewed gene: CLN6: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Ceroid lipofuscinosis, neuronal, 6, 601780; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CLN5 Nicola Ragge reviewed gene: CLN5: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Ceroid lipofuscinosis, neuronal, 5, 256731; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CLN3 Nicola Ragge reviewed gene: CLN3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Ceroid lipofuscinosis, neuronal, 3, 204200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CIB2 Nicola Ragge reviewed gene: CIB2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Usher syndrome, type IJ, 614869; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CHM Nicola Ragge reviewed gene: CHM: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Choroideremia, 303100; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Structural eye disease v0.76 CERKL Nicola Ragge reviewed gene: CERKL: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 26, 608380; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CEP41 Nicola Ragge reviewed gene: CEP41: Rating: RED; Mode of pathogenicity: ; Publications: 22246503; Phenotypes: Joubert syndrome 15, 614464; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CEP290 Nicola Ragge reviewed gene: CEP290: Rating: GREEN; Mode of pathogenicity: ; Publications: 30055837, 22355252; Phenotypes: Joubert syndrome 5, Senior-Loken syndrome 6, Meckel syndrome 4, Leber congenital amaurosis 10, ?Bardet-Biedl syndrome 14, 610188, 610189, 611134, 611755, 615991; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CDHR1 Nicola Ragge reviewed gene: CDHR1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cone-rod dystrophy 15, 613660; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CDH3 Nicola Ragge reviewed gene: CDH3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Ectodermal dysplasia, ectrodactyly, and macular dystrophy, Hypotrichosis, congenital, with juvenile macular dystrophy, 225280, 601553; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CDH23 Nicola Ragge reviewed gene: CDH23: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Usher syndrome, type 1D, 601067; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CACNA2D4 Nicola Ragge reviewed gene: CACNA2D4: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinal cone dystrophy 4, 610478; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CACNA1F Nicola Ragge reviewed gene: CACNA1F: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Night blindness, congenital stationary (incomplete), 2A, X-linked, Cone-rod dystropy, X-linked, 3, Aland Island eye disease, 300071, 300476, 300600; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Structural eye disease v0.76 CABP4 Nicola Ragge reviewed gene: CABP4: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Night blindness, congenital stationary (incomplete), 2B, autosomal recessive, 610427; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CA4 Nicola Ragge reviewed gene: CA4: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 17, 600852; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 C8orf37 Nicola Ragge reviewed gene: C8orf37: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cone-rod dystrophy 16, 614500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 C5orf42 Nicola Ragge reviewed gene: C5orf42: Rating: RED; Mode of pathogenicity: ; Publications: 24178751; Phenotypes: Joubert syndrome 17, 614615; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 C2orf71 Nicola Ragge reviewed gene: C2orf71: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 54, 613428; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 C1QTNF5 Nicola Ragge reviewed gene: C1QTNF5: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinal degeneration, late-onset, autosomal dominant, 605670; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 BMPR1A Nicola Ragge reviewed gene: BMPR1A: Rating: AMBER; Mode of pathogenicity: ; Publications: 29522511; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 BMP7 Nicola Ragge reviewed gene: BMP7: Rating: AMBER; Mode of pathogenicity: other - please provide details in the comments; Publications: 20506283, 7590254; Phenotypes: Microphthalmia, anophthalmia, systemic abnormalities, intellectual disability, None; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 BEST1 Nicola Ragge reviewed gene: BEST1: Rating: GREEN; Mode of pathogenicity: ; Publications: 15452077, 21473666 ; Phenotypes: Vitelliform Macular degeneration 2, Microcornea, rod-cone dystrophy, cataract, and posterior, staphyloma, Bestrophinopathy, autosomal recessive, Retinitis pigmentosa, concentric , 153700, 193220, 611809, 613194; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 BBS9 Nicola Ragge reviewed gene: BBS9: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Bardet-Biedl syndrome9, 615986; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 BBS7 Nicola Ragge reviewed gene: BBS7: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Bardet-Biedl syndrome7, 615984; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 BBS5 Nicola Ragge reviewed gene: BBS5: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Bardet-Biedl syndrome5, 615983; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 BBS4 Nicola Ragge reviewed gene: BBS4: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Bardet-Biedl syndrome4, 615982; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 BBS2 Nicola Ragge reviewed gene: BBS2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Bardet-Biedl syndrome2, Retinitis pigmentosa 74, 615981, 616562; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 BBS12 Nicola Ragge reviewed gene: BBS12: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Bardet-Biedl syndrome12, 615989; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 BBS10 Nicola Ragge reviewed gene: BBS10: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Bardet-Biedl syndrome10, 615987; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 BBS1 Nicola Ragge reviewed gene: BBS1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Bardet-Biedl syndrome1, 209900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 B3GLCT Nicola Ragge reviewed gene: B3GLCT: Rating: GREEN; Mode of pathogenicity: ; Publications: 16909395; Phenotypes: Peters-plus syndrome, 261540; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ATP13A2 Nicola Ragge reviewed gene: ATP13A2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: KUFOR-RAKEB SYNDROME, SPASTIC PARAPLEGIA 78, AUTOSOMAL RECESSIVE, 606693, 617225; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ATOH7 Nicola Ragge reviewed gene: ATOH7: Rating: GREEN; Mode of pathogenicity: ; Publications: 1838, 8779, 22068589, 11493566 ; Phenotypes: Persistent hyperplastic primary vitreous, autosomal recessive (can include microphthalmia), 221900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ASB10 Nicola Ragge reviewed gene: ASB10: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: GLAUCOMA 1, OPEN ANGLE, F, 603383; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 ARL6 Nicola Ragge reviewed gene: ARL6: Rating: RED; Mode of pathogenicity: ; Publications: 19097054; Phenotypes: Retinitis pigmentosa 55, Bardet-Biedl syndrome 3, {Bardet-Biedl syndrome 1, modifier of}, 613575, 600151, 209900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ARL13B Nicola Ragge reviewed gene: ARL13B: Rating: RED; Mode of pathogenicity: ; Publications: 18674751, 25138100; Phenotypes: Joubert syndrome 8, 612291; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ALMS1 Nicola Ragge reviewed gene: ALMS1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Alstrom syndrome, 203800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 AIPL1 Nicola Ragge reviewed gene: AIPL1: Rating: AMBER; Mode of pathogenicity: ; Publications: 25148430; Phenotypes: Cone-rod dystrophy, Leber congenital amaurosis 4, Retinitis pigmentosa, juvenile, 604393, 604393, 604393; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 AHI1 Nicola Ragge reviewed gene: AHI1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Joubert syndrome 3, 608629; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ADGRV1 Nicola Ragge reviewed gene: ADGRV1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Usher syndrome, type 2C, 605472; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ADAM9 Nicola Ragge reviewed gene: ADAM9: Rating: RED; Mode of pathogenicity: ; Publications: 25091951; Phenotypes: Cone-rod dystrophy 9, 612775; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ABHD12 Nicola Ragge reviewed gene: ABHD12: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract , 612674; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ABCB6 Nicola Ragge reviewed gene: ABCB6: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: 22226084; Phenotypes: Microphthalmia, isolated, with coloboma 7, 614497; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 ABCA4 Nicola Ragge reviewed gene: ABCA4: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cone-rod dystrophy 3, Fundus flavimaculatus, Retinal dystrophy, early-onset severe, Retinitis pigmentosa 19, Stargardt disease 1, {Macular degeneration, age-related, 2}, 604116, 248200, 248200, 601718, 248200, 153800; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 TUBGCP4 Nicola Ragge reviewed gene: TUBGCP4: Rating: GREEN; Mode of pathogenicity: ; Publications: 25817018; Phenotypes: Microcephaly and chorioretinopathy, autosomal recessive, 3, 616335; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 SBF2 Nicola Ragge reviewed gene: SBF2: Rating: GREEN; Mode of pathogenicity: ; Publications: 12687498, 15304601; Phenotypes: Charcot-Marie-Tooth disease, type 4B2 604563, CMT with early onset glaucoma; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 RBP4 Nicola Ragge reviewed gene: RBP4: Rating: GREEN; Mode of pathogenicity: ; Publications: 9888420, 27892788, 25910211 ; Phenotypes: Retinal dystrophy, iris coloboma, and comedogenic acne syndrome, 615147; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PIGL Nicola Ragge reviewed gene: PIGL: Rating: GREEN; Mode of pathogenicity: ; Publications: 22444671; Phenotypes: CHIME syndrome, 280000, Coloboma, Congenital Heart Disease, Ichthyosiform Dermatosis,Mental Retardation, and Ear Anomalies Syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 MAF Nicola Ragge reviewed gene: MAF: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: 12642301, 17982426, 16470690; Phenotypes: Cataract 21, multiple types 610202; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 LRP2 Nicola Ragge reviewed gene: LRP2: Rating: GREEN; Mode of pathogenicity: ; Publications: 17632512, 8266995, 18553518; Phenotypes: Donnai-Barrow syndrome, 222448; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 IGBP1 Nicola Ragge reviewed gene: IGBP1: Rating: AMBER; Mode of pathogenicity: ; Publications: 14556245; Phenotypes: Corpus callosum, agenesis of, with mental retardation, ocular coloboma andmicrognathia, 300472; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Structural eye disease v0.76 HMX1 Nicola Ragge reviewed gene: HMX1: Rating: GREEN; Mode of pathogenicity: ; Publications: 18423520, 21417677, 25574057, 29140751; Phenotypes: Oculoauricular syndrome 612109; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 GJA1 Nicola Ragge reviewed gene: GJA1: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: 21273537, 25976645, 15637728, 24508941, 30628995; Phenotypes: Oculodentodigital dysplasia, open angle glaucoma (OAG) and microcornea; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 DDX58 Nicola Ragge reviewed gene: DDX58: Rating: GREEN; Mode of pathogenicity: ; Publications: 25620203, 30574673; Phenotypes: Atypical Singleton-Merton syndrome (AD) - glaucoma and skeletal abnormalities.; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 YAP1 Nicola Ragge reviewed gene: YAP1: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: 24462371, 27267789, 28801591 ; Phenotypes: isolated ocular coloboma, Coloboma, ocular, 120433, Coloboma, ocular, with or without hearing impairment, cleft lip/palate, and/or mentalretardation, 120433; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 VSX2 Nicola Ragge reviewed gene: VSX2: Rating: GREEN; Mode of pathogenicity: ; Publications: 10932181, 20414678 ; Phenotypes: Microphthalmia with coloboma 3, 610092; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 TMEM98 Nicola Ragge reviewed gene: TMEM98: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: 26392740, 24852644; Phenotypes: NNO4, Nanophthalmos 4, 615972; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Structural eye disease v0.76 TBC1D20 Nicola Ragge reviewed gene: TBC1D20: Rating: GREEN; Mode of pathogenicity: ; Publications: 24239381; Phenotypes: Warburg micro syndrome 4, 615663; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 STRA6 Nicola Ragge reviewed gene: STRA6: Rating: GREEN; Mode of pathogenicity: ; Publications: 17273977, 24859618; Phenotypes: Syndromic Microphthalmia, Recessive, Microphthalmia, isolated, with coloboma 8, 601186, Microphthalmia, syndromic 9, 601186; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 SOX2 Nicola Ragge reviewed gene: SOX2: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: 12612584, 24859618; Phenotypes: Microphthalmia, syndromic 3 206900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 SMOC1 Nicola Ragge reviewed gene: SMOC1: Rating: GREEN; Mode of pathogenicity: ; Publications: 21194678, 21194680, 30445150; Phenotypes: Microphthalmia with limb anomalies, 206920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 SMO Nicola Ragge reviewed gene: SMO: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: 27236920; Phenotypes: Curry-Jones syndrome, somatic mosaic 601707; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Structural eye disease v0.76 SIX6 Nicola Ragge reviewed gene: SIX6: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: 23167593, 24702266, 29450879, 15266624; Phenotypes: Microphthalmia with cataract 2, 212550, Optic disc anomalies with retinal and/or macular dystrophy, 212550, Anophthalmia/Microphthalmia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown - Change
Structural eye disease v0.76 SHH Nicola Ragge reviewed gene: SHH: Rating: GREEN; Mode of pathogenicity: ; Publications: 12503095, 20425842; Phenotypes: Holoprosencephaly-3, 142945, Microphthalmia with coloboma 5, 611638, Single median maxillary central incisor, 147250, Schizencephaly, 269160; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Structural eye disease v0.76 SALL4 Nicola Ragge reviewed gene: SALL4: Rating: GREEN; Mode of pathogenicity: ; Publications: 12843316, 6426304; Phenotypes: Duane-radial ray syndrome, 607323; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 RPGRIP1L Nicola Ragge reviewed gene: RPGRIP1L: Rating: GREEN; Mode of pathogenicity: ; Publications: 19574260; Phenotypes: COACH syndrome, 216360; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 RAX Nicola Ragge reviewed gene: RAX: Rating: GREEN; Mode of pathogenicity: ; Publications: 14662654, 18783408, 24033328; Phenotypes: Anophthalmia/Microphthalmia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 RARB Nicola Ragge reviewed gene: RARB: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: 24859618; Phenotypes: Microphthalmia, syndromic 12, 615524; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 RAB3GAP2 Nicola Ragge reviewed gene: RAB3GAP2: Rating: GREEN; Mode of pathogenicity: ; Publications: 23420520; Phenotypes: Martsolf syndrome, 212720Warburg micro syndrome 2, 614225, Warburg Micro Syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 RAB3GAP1 Nicola Ragge reviewed gene: RAB3GAP1: Rating: GREEN; Mode of pathogenicity: ; Publications: 21473985; Phenotypes: Warburg micro syndrome 1, 600118, Warburg Micro Syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 RAB18 Nicola Ragge reviewed gene: RAB18: Rating: GREEN; Mode of pathogenicity: ; Publications: 21473985; Phenotypes: Warburg micro syndrome 3, 614222, Warburg Micro Syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PUF60 Nicola Ragge reviewed gene: PUF60: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: 19464398, 24140112, 27804958, 28327570; Phenotypes: Verheij syndrome, 615583, VRJS, ocular abnormalities, PUF60 syndrome, Chromosome 8q24.3 deletion syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 PRSS56 Nicola Ragge reviewed gene: PRSS56: Rating: GREEN; Mode of pathogenicity: ; Publications: 29450879; Phenotypes: Microphthalmia, isolated 6, 613517; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PORCN Nicola Ragge reviewed gene: PORCN: Rating: GREEN; Mode of pathogenicity: ; Publications: 17546030, 24859618; Phenotypes: Focal dermal hypoplasia 305600; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Structural eye disease v0.76 PITX2 Nicola Ragge reviewed gene: PITX2: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: 9685346, 9618168, 10051017, 8944018, 18723525, 11487566; Phenotypes: Anterior segment dysgenesis 4 137600, Axenfeld-Rieger syndrome, type 1 180500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Structural eye disease v0.76 PAX6 Nicola Ragge reviewed gene: PAX6: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: 12552561, 11826019, 11553050, 17406642, 7666404, 17595013, 8111379, 7550230, 7951315, 9931324, 1302030, 19876904, 17148041; Phenotypes: Anophthalmia, Gillespie syndrome, 206700, Cataract with late-onset corneal dystrohpy, 106210, ?Morning glory disc anomaly, 120430, Aniridia, 106210, Peters anomaly, 604229, Coloboma of optic nerve, 120430, Aniridia 106210, Foveal hypoplasia 1, 136520, Keratitis, 148190, Optic nerve hypoplasia, 165550, Coloboma, ocular, 120200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 PAX2 Nicola Ragge reviewed gene: PAX2: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: 8589702, 22213154, 10533062; Phenotypes: Papillorenal syndrome 120330; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 OTX2 Nicola Ragge reviewed gene: OTX2: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: 15846561, 18781617,24859618; Phenotypes: OTX2-Related Syndromic Microphthalmia, severe, bilateral cases, Microphthalmia, syndromic 5, 610125; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 MYOC Nicola Ragge reviewed gene: MYOC: Rating: GREEN; Mode of pathogenicity: ; Publications: 9535666, 12522550, 9345106, 9328473, 9005853, 9697688, 10330365; Phenotypes: Glaucoma 1A, primary open angle, 137750; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 MFRP Nicola Ragge reviewed gene: MFRP: Rating: GREEN; Mode of pathogenicity: ; Publications: 29450879; Phenotypes: Microphthalmia, isolated 5, 611040, Isolated Microphthalmia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 MAB21L2 Nicola Ragge reviewed gene: MAB21L2: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: 24906020, 25719200; Phenotypes: Microphthalmia, syndromic 14, 615877; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 LTBP2 Nicola Ragge reviewed gene: LTBP2: Rating: GREEN; Mode of pathogenicity: ; Publications: 19656777, 19361779, 21081970, 20179738; Phenotypes: Glaucoma 3, primary congenital, D 613086, Primary Congenital Glaucoma; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 HCCS Nicola Ragge reviewed gene: HCCS: Rating: GREEN; Mode of pathogenicity: ; Publications: 17033964, 24859618; Phenotypes: Linear skin defects with multiple congenital anomalies 1, 309801, Microphthalmia, syndromic 7, 309801; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Structural eye disease v0.76 GRIP1 Nicola Ragge reviewed gene: GRIP1: Rating: GREEN; Mode of pathogenicity: ; Publications: 22510445; Phenotypes: FRASER SYNDROME 3, 617667; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 FREM2 Nicola Ragge reviewed gene: FREM2: Rating: GREEN; Mode of pathogenicity: ; Publications: 15838507; Phenotypes: FRASER SYNDROME 2, 617666; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 FREM1 Nicola Ragge reviewed gene: FREM1: Rating: GREEN; Mode of pathogenicity: ; Publications: 21507892, ; Phenotypes: MANITOBA OCULOTRICHOANAL SYNDROME, 248450; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 FRAS1 Nicola Ragge reviewed gene: FRAS1: Rating: GREEN; Mode of pathogenicity: ; Publications: 12766769; Phenotypes: FRASER SYNDROME 1, 219000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 FOXE3 Nicola Ragge reviewed gene: FOXE3: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: 11159941, 21150893, 27218149, 16826526, 20361012, 24859618, 19708017; Phenotypes: Anterior segment dysgenesis 2, multiple subtypes 610256, Anterior segment mesenchymal dysgenesis 107250; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 FOXD3 Nicola Ragge reviewed gene: FOXD3: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: 22815627; Phenotypes: aniridia, Peters anomaly, Anterior segment dysgenesis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 FOXC1 Nicola Ragge reviewed gene: FOXC1: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: 9620769, 10713890, 12036988, 17210863, 12614756, 11007653; Phenotypes: Anterior segment dysgenesis 3, multiple subtypes 601631, Axenfeld-Rieger syndrome, type 3 602482; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 CYP1B1 Nicola Ragge reviewed gene: CYP1B1: Rating: GREEN; Mode of pathogenicity: ; Publications: 9463332, 9097971, 9497261, 12372064; Phenotypes: Glaucoma 3, Primary Congenital, A, GLC3A, 231300, Peters anomaly, 604229, Glaucoma 3A, primary open angle, congenital, juvenile, or adult onset, primary congenital glaucoma, Primary Congenital Glaucoma; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 COL4A1 Nicola Ragge reviewed gene: COL4A1: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: 24628545, 30181649; Phenotypes: BRAIN SMALL VESSEL DISEASE WITH OR WITHOUT OCULAR ANOMALIES, 607595; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Structural eye disease v0.76 CLDN19 Nicola Ragge reviewed gene: CLDN19: Rating: GREEN; Mode of pathogenicity: ; Publications: 17033971, 500385; Phenotypes: Hypomagnesemia 5, renal, with ocular involvement, 248190; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CHD7 Nicola Ragge reviewed gene: CHD7: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: 16400610; Phenotypes: CHARGE syndrome, 214800; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 CC2D2A Nicola Ragge reviewed gene: CC2D2A: Rating: GREEN; Mode of pathogenicity: ; Publications: 19574260; Phenotypes: COACH syndrome, 216360; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 C12orf57 Nicola Ragge reviewed gene: C12orf57: Rating: GREEN; Mode of pathogenicity: ; Publications: 23453665, 24859618; Phenotypes: Temtamy syndrome, 218340; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 BMP4 Nicola Ragge reviewed gene: BMP4: Rating: AMBER; Mode of pathogenicity: ; Publications: 18252212, 2427285; Phenotypes: Orofacial cleft 11, 600625, BMP4-Related Syndromic Microphthalmia, Microphthalmia, syndromic 6, 607932; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Structural eye disease v0.76 BCOR Nicola Ragge reviewed gene: BCOR: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: 15004558, 17517692, 29974297; Phenotypes: Microphthalmia, syndromic 2, 300166; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Structural eye disease v0.76 ALDH1A3 Nicola Ragge reviewed gene: ALDH1A3: Rating: GREEN; Mode of pathogenicity: ; Publications: 24859610, 23591992; Phenotypes: Microphthalmia, isolated 8 615113; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ADAMTS17 Nicola Ragge reviewed gene: ADAMTS17: Rating: GREEN; Mode of pathogenicity: ; Publications: 19836009; Phenotypes: Weill-Marchesani-like syndrome- lenticular myopia, ectopia lentis, glaucoma, spherophakia, and short stature, but no brachydactyly (AR); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ADAMTS10 Nicola Ragge reviewed gene: ADAMTS10: Rating: GREEN; Mode of pathogenicity: ; Publications: 18567016, 19836009, 15368195; Phenotypes: Weill-Marchesani syndrome 1, recessive; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ACTG1 Nicola Ragge reviewed gene: ACTG1: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: 22366783; Phenotypes: Baraitser-Winter syndrome 2, 614583; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 ACTB Nicola Ragge reviewed gene: ACTB: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: 2505231; Phenotypes: Baraitser-Winter syndrome 1, 243310; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dystonia, chorea or related movement disorder, adult onset v0.87 ATXN1 Louise Daugherty edited their review of gene: ATXN1: Changed rating: RED
Dystonia, chorea or related movement disorder, adult onset v0.87 ATXN1 Louise Daugherty commented on gene: ATXN1: New RED gene added from James Polke (Neurogenetics Laboratory, Institute of Neurology, London), this is likely to relate to the STR ATXN1_CAG and not the gene entity, as there are no SNVs for this gene being associated to the disorder, this gene is rated RED, the STR ATXN1_CAG is rated GREEN. To clarify with the Neurology Test Group in July 2019
Primary lymphoedema v1.38 FLT4 Sarah Leigh Added comment: Comment on phenotypes: Previously known as Milroy disease.
Primary lymphoedema v1.38 FLT4 Sarah Leigh Phenotypes for gene: FLT4 were changed from Lymphedema, hereditary, IA 153100 to Lymphedema, hereditary, IA 153100
Primary lymphoedema v1.37 EPHB4 Sarah Leigh Deleted their review
Primary lymphoedema v1.37 EPHB4 Sarah Leigh Publications for gene: EPHB4 were set to 27400125
Primary lymphoedema v1.36 EPHB4 Sarah Leigh Added comment: Comment on phenotypes: This can manifest with fetal hydrops or Atrial septal defect.
Primary lymphoedema v1.36 EPHB4 Sarah Leigh Phenotypes for gene: EPHB4 were changed from Autosomal Dominant Lymphatic Related Hydrops Fetalis to Lymphatic malformation 7 617300
Retinal disorders v1.140 ABCA4 Ivone Leong Added comment: Comment on mode of inheritance: Changed from both monoallelic and biallelic to just biallelic as adviced by Gavin Arno (UCL Institute of Ophthalmology/Moorfields Eye Hospital). ABCA4 is a susceptibility factor rather than a monogenic cause of macular degeneration; therefore, the monoallelic MOI was removed.
Retinal disorders v1.140 ABCA4 Ivone Leong Mode of inheritance for gene: ABCA4 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Rare multisystem ciliopathy disorders v1.97 LBR Eleanor Williams commented on gene: LBR: Consulting with the Genomics England clinical team as to the appropriate rating for this gene on this panel.
Rare multisystem ciliopathy disorders v1.97 LBR Eleanor Williams commented on gene: LBR
RASopathies v1.53 SPRED1 Sarah Leigh Phenotypes for gene: SPRED1 were changed from Legius Syndrome; Neurofibromatosis-like syndrome to Legius syndrome 611431
RASopathies v1.52 SPRED1 Sarah Leigh Publications for gene: SPRED1 were set to PMID: 17704776; 19366998; 19443465; 21649642; 21548021
RASopathies v1.51 SOS2 Sarah Leigh Phenotypes for gene: SOS2 were changed from Noonan syndrome 9 to Noonan syndrome 9 616559
Congenital hypothyroidism v1.27 SLC26A7 Ivone Leong Classified gene: SLC26A7 as Green List (high evidence)
Congenital hypothyroidism v1.27 SLC26A7 Ivone Leong Added comment: Comment on list classification: Promoted from red to green. SLC26A7 is not associated with a phenotype in OMIM or Gene2Phenotype; however, there is enough evidence to support promoting this gene to green status. PMID: 29546359 describes a Saudi Arabian family with 2 affected daughters who are homozygous for two tandem SLC26A7 deletions (located next to each other). Slc26a7 knockout mice exhibit hypothyroidism and hyperplastic thyroid changes.

PMID: 30333321 describes 6 families with congenital hypothyroidism. 2 Pakistani families with consanguineous parents, 1 Turkish family with consanguineous parents and 3 Finnish families with non-consanguineous parents. The Pakistani and Turkish families have the same homozygous nonsense variant and the Finnish families have the same homozygous frameshift variant. The study also included a Slc26a7-null mouse model that exhibited hypothyoidism phenotype.
Congenital hypothyroidism v1.27 SLC26A7 Ivone Leong Gene: slc26a7 has been classified as Green List (High Evidence).
RASopathies v1.50 SOS1 Sarah Leigh Phenotypes for gene: SOS1 were changed from Noonan syndrome; Noonan syndrome 4 to Noonan syndrome 4 610733
Rare multisystem ciliopathy disorders v1.97 SCLT1 Eleanor Williams Phenotypes for gene: SCLT1 were changed from No OMIM phenotype; Oro-facio-digital syndrome type IX (Adly (2014) Hum Mutat 35,36) to No OMIM phenotype; Oro-facio-digital syndrome type IX; Senior-Løken Syndrome
RASopathies v1.49 SOS1 Sarah Leigh Publications for gene: SOS1 were set to PMID: 19438935; 17143285; 17143282; 17586837
RASopathies v1.48 SHOC2 Sarah Leigh commented on gene: SHOC2
RASopathies v1.48 SHOC2 Sarah Leigh Publications for gene: SHOC2 were set to PMID: 19684605; 22528146; 23918763
Congenital hypothyroidism v1.26 SLC26A7 Ivone Leong Publications for gene: SLC26A7 were set to
RASopathies v1.47 RIT1 Sarah Leigh Publications for gene: RIT1 were set to PMID: 23791108; 25124994; 24939608
RASopathies v1.46 RIT1 Sarah Leigh Phenotypes for gene: RIT1 were changed from Noonan syndrome 8; Noonan syndrome type 8 to Noonan syndrome 8 615355
RASopathies v1.45 RAF1 Sarah Leigh Publications for gene: RAF1 were set to PMID: 17603483; 17603482
RASopathies v1.44 RAF1 Sarah Leigh Phenotypes for gene: RAF1 were changed from Noonan syndrome; Noonan syndrome 5; LEOPARD syndrome; LEOPARD syndrome 2 to LEOPARD syndrome 2 611554; Noonan syndrome 5 611553
RASopathies v1.43 PTPN11 Sarah Leigh Publications for gene: PTPN11 were set to PMID: 17603483; 11704759; 12529711; 12634870; 15384080; 15240615; 16263833; 17497712; 18678287
Rare multisystem ciliopathy disorders v1.96 SCLT1 Eleanor Williams Publications for gene: SCLT1 were set to 15797711
Rare multisystem ciliopathy disorders v1.95 SCLT1 Eleanor Williams Classified gene: SCLT1 as Green List (high evidence)
Rare multisystem ciliopathy disorders v1.95 SCLT1 Eleanor Williams Added comment: Comment on list classification: 3 cases plus a mouse model and functional evidence that the protein is a ciliary protein.
Rare multisystem ciliopathy disorders v1.95 SCLT1 Eleanor Williams Gene: sclt1 has been classified as Green List (High Evidence).
Rare multisystem ciliopathy disorders v1.94 SCLT1 Eleanor Williams commented on gene: SCLT1
Dystonia, chorea or related movement disorder, adult onset v0.87 ATN1 Louise Daugherty edited their review of gene: ATN1: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180) and Hereditary ataxia v1.148 - Brain channelopathy v1.46.
This gene was uploaded from the curation template sent out to the GLHs for GMS Neurology specialist test group as it is a RED gene on the Brain channelopathy panel. The GREEN review from James Polke (Neurogenetics Laboratory, Institute of Neurology, London) is likely to relate to the STR ATN1_CAG and not the gene entity, as there are no SNVs for this gene being associated to the disorder, this gene is rated RED.; Changed rating: RED
Congenital hypothyroidism v1.25 TUBB1 Ivone Leong Classified gene: TUBB1 as Amber List (moderate evidence)
Congenital hypothyroidism v1.25 TUBB1 Ivone Leong Added comment: Comment on list classification: Promoted from red to amber. TUBB1 is not associated with congenital hypothyroidism in OMIM or Gene2Phenotype. PMID: 30446499 reported on 3 unrelated families with affected individuals who have different variants in TUBB1.

Family #1: consanguineous family of Algerian descent with 3 out of 5 children affected by disease. All 3 children are homozygous for a missense variant and both parents are heterozygous.

Family #2: Moroccan father and French mother with 1 affected child (3 children in total). The affected child is heterozygous for a nonsense variant. The father has the same heterozygous variant, but no tests could be done to confirm phenotype. A paternal aunt with the same heterozygous variant also presented with disease.

Family #3: French family with 1 affected child (3 children in total). Affected child is heterozygous for a frameshift variant. The father has the same heterozygous variant but has normal thyroid function (did not present with disease).

Knockout mouse model showed a thyroid phenotype.

Due to the evidence from family #2 and #3 it was decided that there was not yet enough evidence to promote TUBB1 to green gene status.
Congenital hypothyroidism v1.25 TUBB1 Ivone Leong Gene: tubb1 has been classified as Amber List (Moderate Evidence).
Hereditary ataxia, adult onset v1.171 TUBB2A Louise Daugherty Mode of inheritance for gene: TUBB2A was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia, adult onset v1.170 TUBB Louise Daugherty Mode of pathogenicity for gene: TUBB was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Hereditary ataxia, adult onset v1.169 TUBB Louise Daugherty Mode of inheritance for gene: TUBB was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia, adult onset v1.168 TUBA8 Louise Daugherty Mode of inheritance for gene: TUBA8 was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary ataxia, adult onset v1.167 THG1L Louise Daugherty Mode of inheritance for gene: THG1L was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary ataxia, adult onset v1.166 TBP Louise Daugherty reviewed gene: TBP: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Hereditary ataxia, adult onset v1.166 SMPD4 Louise Daugherty edited their review of gene: SMPD4: Added comment: To clarify, this gene was uploaded by the GLH from a gene list submitted for R54. The gene SMPD4 is rated Amber on the following Rare Disease 100K PanelApp panels : Cerebellar hypoplasia, Arthrogryposis, Intellectual disabilit, due to work presented at ESHG 2018 by Pamela Magini: three unrelated families with ID, cerebellar hypoplasia, arthrogryposis. Still unpublished.; Changed rating: RED
Hereditary ataxia, adult onset v1.166 SLC25A32 Louise Daugherty Mode of inheritance for gene: SLC25A32 was changed from to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v1.394 VPS13C Sarah Leigh Classified gene: VPS13C as Red List (low evidence)
Mitochondrial disorders v1.394 VPS13C Sarah Leigh Added comment: Comment on list classification: This gene was demoted from Green to Red, based on the reviews of clinical experts.
Mitochondrial disorders v1.394 VPS13C Sarah Leigh Gene: vps13c has been classified as Red List (Low Evidence).
Hereditary ataxia, adult onset v1.165 PPP2R2B Louise Daugherty reviewed gene: PPP2R2B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mitochondrial disorders v1.393 GLUD1 Sarah Leigh Classified gene: GLUD1 as Red List (low evidence)
Mitochondrial disorders v1.393 GLUD1 Sarah Leigh Added comment: Comment on list classification: This gene was demoted from Green to Red, based on the reviews of clinical experts.
Mitochondrial disorders v1.393 GLUD1 Sarah Leigh Gene: glud1 has been classified as Red List (Low Evidence).
Hereditary ataxia, adult onset v1.165 PI4KA Louise Daugherty Mode of inheritance for gene: PI4KA was changed from to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v1.392 DHTKD1 Sarah Leigh Classified gene: DHTKD1 as Red List (low evidence)
Mitochondrial disorders v1.392 DHTKD1 Sarah Leigh Added comment: Comment on list classification: This gene was demoted from Green to Red, based on the reviews of clinical experts.
Mitochondrial disorders v1.392 DHTKD1 Sarah Leigh Gene: dhtkd1 has been classified as Red List (Low Evidence).
Hereditary ataxia, adult onset v1.164 PAX2 Louise Daugherty Phenotypes for gene: PAX2 were changed from Ataxia,spastic2,autosomalrecessive(2); Papillorenal syndrome, AR to Ataxia,spastic2,autosomal recessive; Papillorenal syndrome, AR
Hereditary ataxia, adult onset v1.163 PAX2 Louise Daugherty Mode of inheritance for gene: PAX2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mitochondrial disorders v1.391 DARS Sarah Leigh Classified gene: DARS as Red List (low evidence)
Mitochondrial disorders v1.391 DARS Sarah Leigh Added comment: Comment on list classification: This gene was demoted from Green to Red, based on the reviews of clinical experts.
Mitochondrial disorders v1.391 DARS Sarah Leigh Gene: dars has been classified as Red List (Low Evidence).
Hereditary ataxia, adult onset v1.162 MME Louise Daugherty Mode of inheritance for gene: MME was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia, adult onset v1.161 GLI3 Louise Daugherty Mode of inheritance for gene: GLI3 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia, adult onset v1.160 FRMD4A Louise Daugherty Mode of inheritance for gene: FRMD4A was changed from to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v1.390 CHKB Sarah Leigh Classified gene: CHKB as Red List (low evidence)
Mitochondrial disorders v1.390 CHKB Sarah Leigh Added comment: Comment on list classification: This gene was demoted from Green to Red, based on the reviews of clinical experts.
Mitochondrial disorders v1.390 CHKB Sarah Leigh Gene: chkb has been classified as Red List (Low Evidence).
Hereditary ataxia, adult onset v1.159 DMXL2 Louise Daugherty Mode of inheritance for gene: DMXL2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Hereditary ataxia, adult onset v1.158 DCC Louise Daugherty Mode of inheritance for gene: DCC was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mitochondrial disorders v1.389 C19orf12 Sarah Leigh Classified gene: C19orf12 as Red List (low evidence)
Mitochondrial disorders v1.389 C19orf12 Sarah Leigh Added comment: Comment on list classification: This gene was demoted from Green to Red, based on the reviews of clinical experts.
Mitochondrial disorders v1.389 C19orf12 Sarah Leigh Gene: c19orf12 has been classified as Red List (Low Evidence).
Mitochondrial disorders v1.388 VPS13C Anna de Burca reviewed gene: VPS13C: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Parkinson disease 23, autosomal recessive, early onset, 616840; Mode of inheritance:
Mitochondrial disorders v1.388 TANGO2 Anna de Burca reviewed gene: TANGO2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration, 616878; Mode of inheritance:
Mitochondrial disorders v1.388 STAT2 Anna de Burca reviewed gene: STAT2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Immunodeficiency 44, 616636; Mode of inheritance:
Mitochondrial disorders v1.388 ROBO3 Anna de Burca reviewed gene: ROBO3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Gaze palsy, familial horizontal, with progressive scoliosis, 1, 607313; Mode of inheritance:
Mitochondrial disorders v1.388 IER3IP1 Anna de Burca reviewed gene: IER3IP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Microcephaly, epilepsy, and diabetes syndrome, 614231; Mode of inheritance:
Mitochondrial disorders v1.388 HMGCL Anna de Burca reviewed gene: HMGCL: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: HMG-CoA lyase deficiency, 246450; Mode of inheritance:
Mitochondrial disorders v1.388 GLUD1 Anna de Burca reviewed gene: GLUD1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Hyperinsulinism-hyperammonemia syndrome, 606762; Mode of inheritance:
Mitochondrial disorders v1.388 FXN Anna de Burca reviewed gene: FXN: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Friedreich ataxia, 229300; Mode of inheritance:
Mitochondrial disorders v1.388 DHTKD1 Anna de Burca reviewed gene: DHTKD1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: 2-aminoadipic 2-oxoadipic aciduria, 204750, ?Charcot-Marie-Tooth disease, axonal, type 2Q 615025; Mode of inheritance:
Mitochondrial disorders v1.388 DARS Anna de Burca reviewed gene: DARS: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Hypomyelination with brainstem and spinal cord involvement and leg spasticity, 615281; Mode of inheritance:
Mitochondrial disorders v1.388 CHKB Anna de Burca reviewed gene: CHKB: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Muscular dystrophy, congenital, megaconial type, 602541; Mode of inheritance:
Mitochondrial disorders v1.388 C19orf12 Anna de Burca reviewed gene: C19orf12: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Neurodegeneration with brain iron accumulation 4, 614298, ?Spastic paraplegia 43, autosomal recessive, 615043; Mode of inheritance:
Hereditary ataxia, adult onset v1.157 DAB1 Louise Daugherty edited their review of gene: DAB1: Added comment: New gene added by Wessex and West Midlands GLH and London North GLH. Gene and Green rating to be discussed by the Neurology Test Group in July 2019 - since this relates to repeat STR entity and not a gene entity. DAB1 STR has not yet been validated by the pipeline.; Changed rating: RED
Hereditary ataxia, adult onset v1.157 BEAN1 Louise Daugherty commented on gene: BEAN1: New gene added by Wessex and West Midlands GLH and London North GLH. Gene and Green rating to be discussed by the Neurology Test Group in July 2019 - since this relates to repeat STR entity and not a gene entity. BEAN1 STR has not yet been validated by the pipeline.
Hereditary ataxia, adult onset v1.157 B3GALNT2 Louise Daugherty Classified gene: B3GALNT2 as Green List (high evidence)
Hereditary ataxia, adult onset v1.157 B3GALNT2 Louise Daugherty Added comment: Comment on list classification: New gene added by Wessex and West Midlands GLH. Gene and Green rating to be discussed by the Neurology Test Group in July 2019.
Hereditary ataxia, adult onset v1.157 B3GALNT2 Louise Daugherty Gene: b3galnt2 has been classified as Green List (High Evidence).
Hereditary ataxia, adult onset v1.156 B3GALNT2 Louise Daugherty Mode of inheritance for gene: B3GALNT2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary ataxia, adult onset v1.155 ATXN7 Louise Daugherty edited their review of gene: ATXN7: Added comment: This gene was uploaded from the curation template sent out to the GLHs for GMS Neurology specialist test group. The GREEN review from Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust) on behalf of Wessex and West Midlands GLH relates to the STR and not the gene entity
(and is indicated in her comments), as there are no SNVs for this gene being associated to the disorder, this gene is rated RED.; Changed rating: RED
Hereditary ataxia, adult onset v1.155 ATXN3 Louise Daugherty edited their review of gene: ATXN3: Added comment: This gene was uploaded from the curation template sent out to the GLHs for GMS Neurology specialist test group. The GREEN review from Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust) on behalf of Wessex and West Midlands GLH relates to the STR and not the gene entity (and is indicated in her comments), as there are no SNVs for this gene being associated to the disorder, this gene is rated RED.; Changed rating: RED
Hereditary ataxia, adult onset v1.155 ATXN2 Louise Daugherty edited their review of gene: ATXN2: Added comment: This gene was uploaded from the curation template sent out to the GLHs for GMS Neurology specialist test group. The GREEN review from Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust) on behalf of Wessex and West Midlands GLH relates to the STR and not the gene (and is indicated in her comments), as there are no SNVs for this gene being associated to the disorder, this gene is rated RED.; Changed rating: RED
Hereditary ataxia, adult onset v1.155 ATXN10 Louise Daugherty edited their review of gene: ATXN10: Added comment: This gene was uploaded from the curation template sent out to the GLHs for GMS Neurology specialist test group. The GREEN review from Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust) on behalf of Wessex and West Midlands GLH relates to the STR and not the gene (and is indicated in her comments), as there are no SNVs for this gene being associated to the disorder, this gene is rated RED.; Changed rating: RED
Hereditary ataxia, adult onset v1.155 ATXN1 Louise Daugherty edited their review of gene: ATXN1: Added comment: This gene was uploaded from the curation template sent out to the GLHs for GMS Neurology specialist test group. The Green review from Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust) on behalf of Wessex and West Midlands GLH relates to the STR and not the gene (and is indicated in her comments), as there are no SNVs for this gene being associated to the disorder, this gene is rated RED.; Changed rating: RED
Hereditary ataxia, adult onset v1.155 ATN1 Louise Daugherty edited their review of gene: ATN1: Added comment: This gene was uploaded from the curation template sent out to the GLHs for GMS Neurology specialist test group. The Green review from Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust) on behalf of Wessex and West Midlands GLH relates to the STR and not the gene (and is indicated in her comments), as there are no SNVs for this gene being associated to the disorder, this gene is rated RED.; Changed rating: RED
Early onset or syndromic epilepsy v1.62 ALKBH8 Catherine Snow commented on gene: ALKBH8: Expert review by Konstantinos Varvagiannis on ALKBH8. Monies et al. (2019 - PMID: 31079898) report on 7 individuals from 2 different consanguineous Saudi families, harboring homozygous truncating ALKBH8 pathogenic variants. The same individuals are included in another concurrent publication from the same group (Monies et al. 2019 - PMID: 31130284).

Epilepsy was reported for 6/7 individuals although the type has not been commented on (onset 9-12 months to 2 years). Variable other phenotype features were noted in few.

ALKBH8 is not currently associated with any phenotype in OMIM / G2P.


ALKBH8 can be included in the epilepsy panel as Amber awaiting further evidence and tagged on the watchlist.
Early onset or syndromic epilepsy v1.62 ALKBH8 Catherine Snow reviewed gene: ALKBH8: Rating: AMBER; Mode of pathogenicity: None; Publications: 31079898; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary ataxia, adult onset v1.155 ISCA-37478-Loss Louise Daugherty commented on Region: ISCA-37478-Loss
Hereditary ataxia, adult onset v1.155 ISCA-37478-Gain Louise Daugherty commented on Region: ISCA-37478-Gain: This panel was initially created as a merge of genomic entities form the following Rare Disease 100K two panels : Hereditary ataxia v1.148 and Brain channelopathy v1.46.
This region (rated Green) comes from the Hereditary ataxia v1.148 panel and will need to discussed by the Neurology Test Group in July 2019.
Hereditary ataxia, adult onset v1.155 ISCA-37404-Loss Louise Daugherty commented on Region: ISCA-37404-Loss: This panel was initially created as a merge of genomic entities form the following Rare Disease 100K two panels : Hereditary ataxia v1.148 and Brain channelopathy v1.46.
This region (rated Green) comes from the Hereditary ataxia v1.148 panel and will need to discussed by the Neurology Test Group in July 2019.
Hereditary ataxia, adult onset v1.155 ISCA-37468-Loss Louise Daugherty commented on Region: ISCA-37468-Loss: This panel was initially created as a merge of genomic entities form the following Rare Disease 100K two panels: Hereditary ataxia v1.148 and Brain channelopathy v1.46. This region (rated Green) comes from the Brain channelopathy v1.46 panel, and will need to discussed for inclusion on this panel by the Neurology Test Group in July 2019.
Intellectual disability v2.876 MED12L Eleanor Williams Classified gene: MED12L as Amber List (moderate evidence)
Intellectual disability v2.876 MED12L Eleanor Williams Added comment: Comment on list classification: Rating Amber. CNVs encompass other genes. Two cases with SNVs have moderate/severe ID and one of these also has a VUS in TUBB2B. The other two SNV cases have mild ID.
Intellectual disability v2.876 MED12L Eleanor Williams Gene: med12l has been classified as Amber List (Moderate Evidence).
Intellectual disability v2.875 MED12L Eleanor Williams commented on gene: MED12L
Early onset or syndromic epilepsy v1.62 SLC35A2 Eleanor Williams Phenotypes for gene: SLC35A2 were changed from Congenital disorder of glycosylation, type IIm, 300896 (includes Epileptic encephalopathy); Epileptic encephalopathy, early infantile, 22 (EIEE22); early-onset epileptic encephalopathy to Congenital disorder of glycosylation, type IIm, 300896 (includes Epileptic encephalopathy); Epileptic encephalopathy, early infantile, 22 (EIEE22); early-onset epileptic encephalopathy; epilepsy
Early onset or syndromic epilepsy v1.61 SLC35A2 Eleanor Williams Publications for gene: SLC35A2 were set to 24115232; 27743886
Early onset or syndromic epilepsy v1.60 PIGQ Eleanor Williams Phenotypes for gene: PIGQ were changed from Intractable seizures; developmental delay; optic atrophy to Intractable seizures; developmental delay; optic atrophy; epilepsy; Ohtahara syndrome
Early onset or syndromic epilepsy v1.59 PIGQ Eleanor Williams Publications for gene: PIGQ were set to 24463883; 25558065
Early onset or syndromic epilepsy v1.58 PIGQ Eleanor Williams Classified gene: PIGQ as Green List (high evidence)
Early onset or syndromic epilepsy v1.58 PIGQ Eleanor Williams Added comment: Comment on list classification: 3 cases plus some functional data.
Early onset or syndromic epilepsy v1.58 PIGQ Eleanor Williams Gene: pigq has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v1.57 PIGQ Eleanor Williams commented on gene: PIGQ
Intellectual disability v2.875 KMT5B Eleanor Williams Deleted their comment
Intellectual disability v2.875 KMT5B Eleanor Williams Deleted their comment
Congenital hypothyroidism v1.24 IRS4 Ivone Leong Classified gene: IRS4 as Green List (high evidence)
Congenital hypothyroidism v1.24 IRS4 Ivone Leong Added comment: Comment on list classification: Promoted from red to green. IRS4 is not associated with a phenotype in OMIM or Gene2Phenotype. PMID: 30061370 reported on 5 Dutch families (paper didn't mention whether they are are unrelated or not) with different variants in the gene. The different variants are nonsense and frameshift variants. The paper also describe results from a knockout mouse model that did not show any signs of disease, which is contradictory to the knockout mouse model described in PMID: 10644546, which showed mild metabolic differences to WT controls. However, despite the mouse results there is enough evidence to support promoting this gene to grene status.
Congenital hypothyroidism v1.24 IRS4 Ivone Leong Gene: irs4 has been classified as Green List (High Evidence).
Congenital hypothyroidism v1.23 IRS4 Ivone Leong Publications for gene: IRS4 were set to 30061370
Congenital hypothyroidism v1.22 ISCA-37478-Loss Ivone Leong Classified Region: ISCA-37478-Loss as Amber List (moderate evidence)
Congenital hypothyroidism v1.22 ISCA-37478-Loss Ivone Leong Added comment: Comment on list classification: Demoted from green to amber as adviced by Nadia Schoenmakers (East of England GLH).
Congenital hypothyroidism v1.22 ISCA-37478-Loss Ivone Leong Region: isca-37478-loss has been classified as Amber List (Moderate Evidence).
Congenital hypothyroidism v1.21 ISCA-37404-Loss Ivone Leong Classified Region: ISCA-37404-Loss as Amber List (moderate evidence)
Congenital hypothyroidism v1.21 ISCA-37404-Loss Ivone Leong Added comment: Comment on list classification: Demoted from green to amber as adviced by Nadia Schoenmakers (East of England GLH).
Congenital hypothyroidism v1.21 ISCA-37404-Loss Ivone Leong Region: isca-37404-loss has been classified as Amber List (Moderate Evidence).
Proteinuric renal disease v1.107 LMX1B Eleanor Williams Phenotypes for gene: LMX1B were changed from to Nail-patella syndrome #161200; FSGS; proteinuria; kidney failure; isolated glomerulopathy
Proteinuric renal disease v1.106 LMX1B Eleanor Williams Publications for gene: LMX1B were set to
Proteinuric renal disease v1.105 LAMB2 Eleanor Williams Publications for gene: LAMB2 were set to
Proteinuric renal disease v1.104 LAMB2 Eleanor Williams Phenotypes for gene: LAMB2 were changed from to Nephrotic syndrome, type 5, with or without ocular abnormalities #614199; Pierson syndrome #609049
Proteinuric renal disease v1.103 INF2 Eleanor Williams Publications for gene: INF2 were set to
Proteinuric renal disease v1.102 INF2 Eleanor Williams Phenotypes for gene: INF2 were changed from to Glomerulosclerosis, focal segmental, 5 #613237; Adult onset nephrotic syndrome (+CMT); FSGS; proteinuria; renal failure
Proteinuric renal disease v1.101 CUBN Eleanor Williams Publications for gene: CUBN were set to 21903995
Proteinuric renal disease v1.100 COQ6 Eleanor Williams Phenotypes for gene: COQ6 were changed from to Coenzyme Q10 deficiency, primary, 6 #614650
Proteinuric renal disease v1.99 COQ6 Eleanor Williams Publications for gene: COQ6 were set to
Proteinuric renal disease v1.98 COQ2 Eleanor Williams Publications for gene: COQ2 were set to 17855635; 29637272; 30180404
Proteinuric renal disease v1.98 COQ2 Eleanor Williams Phenotypes for gene: COQ2 were changed from Coenzyme Q10 deficiency, primary, 1 #607426 to Coenzyme Q10 deficiency, primary, 1 #607426
Proteinuric renal disease v1.97 COQ2 Eleanor Williams Phenotypes for gene: COQ2 were changed from to Coenzyme Q10 deficiency, primary, 1 #607426
Proteinuric renal disease v1.96 COQ2 Eleanor Williams Publications for gene: COQ2 were set to PubMed: 17855635
Proteinuric renal disease v1.95 COL4A5 Eleanor Williams Phenotypes for gene: COL4A5 were changed from to Alports; Familial benign haematuria; Alport syndrome; proteinuria; haematuria; FSGS
Proteinuric renal disease v1.94 COL4A5 Eleanor Williams Publications for gene: COL4A5 were set to
Proteinuric renal disease v1.93 COL4A4 Eleanor Williams Publications for gene: COL4A4 were set to
Proteinuric renal disease v1.92 COL4A3 Eleanor Williams Phenotypes for gene: COL4A3 were changed from to Alport syndrome, autosomal dominant #104200; Alport syndrome, autosomal recessive #203780; Hematuria, benign familial #141200
Proteinuric renal disease v1.91 COL4A3 Eleanor Williams Publications for gene: COL4A3 were set to
Proteinuric renal disease v1.90 CLCN5 Eleanor Williams Publications for gene: CLCN5 were set to
Proteinuric renal disease v1.89 ACTN4 Eleanor Williams Phenotypes for gene: ACTN4 were changed from to Glomerulosclerosis, focal segmental, 1 603278
Proteinuric renal disease v1.88 ACTN4 Eleanor Williams Publications for gene: ACTN4 were set to 10700177; 26301083; J Am Soc Nephrol 16: 3694–3701, 2005. doi: 10.1681/ASN.2005070706; 29043128
Proteinuric renal disease v1.87 ACTN4 Eleanor Williams Publications for gene: ACTN4 were set to 10700177; 26301083; J Am Soc Nephrol 16: 3694–3701, 2005. doi: 10.1681/ASN.2005070706; 29043128
Proteinuric renal disease v1.86 ACTN4 Eleanor Williams Publications for gene: ACTN4 were set to PubMed: 10700177; 26301083; J Am Soc Nephrol 16: 3694–3701, 2005. doi: 10.1681/ASN.2005070706
Renal tubulopathies v1.81 GATM Eleanor Williams Phenotypes for gene: GATM were changed from to Renal fanconi syndrome and kidney failure (no MIM number); Cerebral creatine deficiency syndrome 3, 612718 (AR)
Renal tubulopathies v1.80 GATM Eleanor Williams Publications for gene: GATM were set to
Renal tubulopathies v1.79 GNAS Eleanor Williams Phenotypes for gene: GNAS were changed from to Unexplained hyponatremia in infancy, severe early-onset gonadotrophin-independent precocious puberty and skeletal abnormalities.
Renal tubulopathies v1.78 GNAS Eleanor Williams Publications for gene: GNAS were set to
Renal tubulopathies v1.77 MAGED2 Eleanor Williams Phenotypes for gene: MAGED2 were changed from to Bartter syndrome, type 5, antenatal, transient, 300971
Renal tubulopathies v1.76 MAGED2 Eleanor Williams Publications for gene: MAGED2 were set to
Renal tubulopathies v1.75 FOXI1 Eleanor Williams Phenotypes for gene: FOXI1 were changed from deafness; renal tubular acidosis to deafness; renal tubular acidosis; Early onset sensorinerual deafness and distal renal tubular acidosis (no OMIM number); Enlarged vestibular aqueducts, 6007910
Renal tubulopathies v1.74 ATP1A1 Eleanor Williams Phenotypes for gene: ATP1A1 were changed from to Renal hypomagnesemia, refractory seizures and intellectual disability (no OMIM number); Charcot-Marie-Tooth disease, axonal, type 2DD, 618036
Renal tubulopathies v1.73 ATP1A1 Eleanor Williams Publications for gene: ATP1A1 were set to
Renal tubulopathies v1.72 CLDN10 Eleanor Williams Phenotypes for gene: CLDN10 were changed from to Hypokalemic-alkalotic salt-losing tubulopathy (no OMIM number); HELIX syndrome, 617671
Renal tubulopathies v1.71 CLDN10 Eleanor Williams Publications for gene: CLDN10 were set to
Renal tubulopathies v1.70 WNK4 Eleanor Williams Phenotypes for gene: WNK4 were changed from to Pseudohypoaldosteronism, type IIB, 614491
Renal tubulopathies v1.69 WNK1 Eleanor Williams Phenotypes for gene: WNK1 were changed from to Pseudohypoaldosteronism, type IIC, 614492; Neuropathy, hereditary sensory and autonomic, type II, 201300 (AR)
Renal tubulopathies v1.68 UMOD Eleanor Williams Phenotypes for gene: UMOD were changed from to Hyperuricemic nephropathy, familial juvenile 1, 162000; Glomerulocystic kidney disease with hyperuricemia and isosthenuria, 609886; Medullary cystic kidney disease 2, 603860
Renal tubulopathies v1.67 TRPM6 Eleanor Williams Phenotypes for gene: TRPM6 were changed from 602014 to Hypomagnesemia 1, intestinal, 602014
Renal tubulopathies v1.66 SLC9A3R1 Eleanor Williams Phenotypes for gene: SLC9A3R1 were changed from to Nephrolithiasis/osteoporosis, hypophosphatemic, 2, 612287
Renal tubulopathies v1.65 SLC5A2 Eleanor Williams Phenotypes for gene: SLC5A2 were changed from to Renal glucosuria, 233100
Renal tubulopathies v1.64 SLC4A1 Eleanor Williams Phenotypes for gene: SLC4A1 were changed from Distal Renal Tubular Acidosis, Dominant; Ovalocytosis; Distal renal tubular acidosis to Distal Renal Tubular Acidosis, Dominant; Ovalocytosis; Distal renal tubular acidosis; Renal tubular acidosis, distal, AD,179800; Renal tubular acidosis, distal, AR, 611590; Cryohydrocytosis, 185020; Ovalocystois, SA type 166900; Spherocytoisis type 4, 612653; various blood group associations.
Renal tubulopathies v1.63 SLC4A1 Eleanor Williams Publications for gene: SLC4A1 were set to
Renal tubulopathies v1.62 SLC34A3 Eleanor Williams Phenotypes for gene: SLC34A3 were changed from to Hypophosphatemic rickets with hypercalciuria, 241530
Renal tubulopathies v1.61 SLC34A1 Eleanor Williams Phenotypes for gene: SLC34A1 were changed from to Hypercalcemia, infantile, 2, MIM 616963; Nephrolithiasis/osteoporosis, hypophosphatemic, 1, 612286; ?Fanconi renotubular syndrome 2 613388
Renal tubulopathies v1.60 SLC2A9 Eleanor Williams Phenotypes for gene: SLC2A9 were changed from to Hypouricemia, renal, 2, 612076; {Uric acid concentration, serum, QTL 2}, 612076
Congenital hypothyroidism v1.20 SLC26A7 Nadia Schoenmakers reviewed gene: SLC26A7: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Primary congenital hypothyroidism (dyshormonogenesis), OMIM 608479; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital hypothyroidism v1.20 TUBB1 Nadia Schoenmakers reviewed gene: TUBB1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: Primary congenital hypothyroidism, thyroid dysgenesis, macroplatelets; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital hypothyroidism v1.20 IRS4 Nadia Schoenmakers reviewed gene: IRS4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Congenital central hypothyroidism OMIM 300904; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Congenital hypothyroidism v1.19 SLC26A7 Ivone Leong gene: SLC26A7 was added
gene: SLC26A7 was added to Congenital hypothyroidism. Sources: East of England GLH
Mode of inheritance for gene: SLC26A7 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC26A7 were set to Primary congenital hypothyroidism (dyshormonogenesis)
Congenital hypothyroidism v1.19 TUBB1 Ivone Leong gene: TUBB1 was added
gene: TUBB1 was added to Congenital hypothyroidism. Sources: East of England GLH
Mode of inheritance for gene: TUBB1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TUBB1 were set to 30446499
Phenotypes for gene: TUBB1 were set to Primary congenital hypothyroidism, thyroid dysgenesis, macroplatelets
Congenital hypothyroidism v1.19 IRS4 Ivone Leong gene: IRS4 was added
gene: IRS4 was added to Congenital hypothyroidism. Sources: East of England GLH
Mode of inheritance for gene: IRS4 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: IRS4 were set to 30061370
Phenotypes for gene: IRS4 were set to Congenital central hypothyroidism
Rare multisystem ciliopathy disorders v1.94 WDR60 Eleanor Williams Phenotypes for gene: WDR60 were changed from Short-rib thoracic dysplasia 8 with or without polydactyly, 615503; Jeune syndrome; Short-rib thoracic dysplasia 8 with or without polydactyly to Short-rib thoracic dysplasia 8 with or without polydactyly, 615503; Jeune syndrome; Short-rib thoracic dysplasia 8 with or without polydactyly; SHORT-RIB POLYDACTYLY
Rare multisystem ciliopathy disorders v1.93 WDR60 Eleanor Williams Publications for gene: WDR60 were set to 23910462
Rare multisystem ciliopathy disorders v1.92 WDR60 Eleanor Williams Classified gene: WDR60 as Green List (high evidence)
Rare multisystem ciliopathy disorders v1.92 WDR60 Eleanor Williams Added comment: Comment on list classification: More than 3 unrelated cases now reported
Rare multisystem ciliopathy disorders v1.92 WDR60 Eleanor Williams Gene: wdr60 has been classified as Green List (High Evidence).
Rare multisystem ciliopathy disorders v1.91 WDR60 Eleanor Williams commented on gene: WDR60
Anophthalmia or microphthalmia v1.20 KMT2D Ivone Leong Classified gene: KMT2D as Green List (high evidence)
Anophthalmia or microphthalmia v1.20 KMT2D Ivone Leong Added comment: Comment on list classification: Added to the panel as a Green gene. KMT2D is associated to a phenotype in both OMIM and Gene2Phenotype. There is sufficient evidence to support gene-disease phenotype for this gene and the Clinical team at Genomics England agrees that this gene is relevant for this panel.
Anophthalmia or microphthalmia v1.20 KMT2D Ivone Leong Gene: kmt2d has been classified as Green List (High Evidence).
Anophthalmia or microphthalmia v1.19 KMT2D Ivone Leong Phenotypes for gene: KMT2D were changed from microphthalmia to microphthalmia; Kabuki syndrome 1, 147920
Anophthalmia or microphthalmia v1.18 KMT2D Ivone Leong Publications for gene: KMT2D were set to PMID: 26049589; 27530281
Intellectual disability v2.875 CNOT1 Rebecca Foulger Classified gene: CNOT1 as Green List (high evidence)
Intellectual disability v2.875 CNOT1 Rebecca Foulger Added comment: Comment on list classification: Promoted to green on advice from Helen Brittain (Genomics England Clinical Fellow)- there are 3+ cases with a range of causative variants and a relevant phenotype.
Intellectual disability v2.875 CNOT1 Rebecca Foulger Gene: cnot1 has been classified as Green List (High Evidence).
Fetal anomalies v0.284 CNOT1 Rebecca Foulger commented on gene: CNOT1: Keep as amber and added watchlist tag on advice from Helen Brittain (Genomics England Clinical Fellow);this might be a specific variant-related phenotype, and there is insufficient evidence for the gene in general at present.
Holoprosencephaly v1.13 CNOT1 Rebecca Foulger Tag watchlist tag was added to gene: CNOT1.
Holoprosencephaly v1.13 CNOT1 Rebecca Foulger commented on gene: CNOT1: Keep as amber on advice from Helen Brittain (Genomics England Clinical Fellow), and added watchlist tag; this might be a specific variant-related phenotype.
Familial hypercholesterolaemia v1.21 CYP27A1 Philip Dawson reviewed gene: CYP27A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24442603: 29484516; Phenotypes: Cerebrotendinous xanthomatosis, 213700, Tendon Xanthomas, suspected FH; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.87 ISPD Chiara Marini Bettolo commented on gene: ISPD: this gene is listed on the LGMD classification
https://www.nmd-journal.com/article/S0960-8966(18)30214-1/pdf
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.87 DES Chiara Marini Bettolo commented on gene: DES: this gene is currently provided as part of our diagnostic service and is listed on the LGMD classification
https://www.nmd-journal.com/article/S0960-8966(18)30214-1/pdf
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.87 HNRNPDL Chiara Marini Bettolo commented on gene: HNRNPDL: this gene is now listed on the old and new classification for LGMD (LGMD D3)

https://doi.org/10.1016/j.nmd.2018.05.007
Renal tubulopathies v1.59 SLC22A12 Eleanor Williams Phenotypes for gene: SLC22A12 were changed from to Hypouricemia, renal, 220150
Renal tubulopathies v1.58 SLC12A3 Eleanor Williams Phenotypes for gene: SLC12A3 were changed from Hypokalaemic alkalosis with hypomagnesaemia & hypocalciuria to Hypokalaemic alkalosis with hypomagnesaemia & hypocalciuria; Gitelman syndrome, 263800
Renal tubulopathies v1.57 SLC12A1 Eleanor Williams Phenotypes for gene: SLC12A1 were changed from Type 1 Bartter syndrome: infantile onset, pregnancy noted for polyhydramnios. Hyperprostagladinuria. Hypokalaemia and metabolic alkalosis +/- nephrocalcinosis. to Type 1 Bartter syndrome: infantile onset, pregnancy noted for polyhydramnios. Hyperprostagladinuria. Hypokalaemia and metabolic alkalosis +/- nephrocalcinosis; Bartter syndrome, type 1, 601678
Renal tubulopathies v1.56 SCNN1G Eleanor Williams Phenotypes for gene: SCNN1G were changed from to Pseudohypoaldosteronism, type I, 264350
Renal tubulopathies v1.55 SCNN1B Eleanor Williams Phenotypes for gene: SCNN1B were changed from genes for Liddle, GRA, PHA1, hypomagnesemia without stones, AME are all missing to genes for Liddle, GRA, PHA1, hypomagnesemia without stones, AME are all missing; Pseudohypoaldosteronism, type I, 264350
Renal tubulopathies v1.54 SCNN1A Eleanor Williams Phenotypes for gene: SCNN1A were changed from to Pseudohypoaldosteronism, type I, 264350; ?Liddle syndrom 3, 618126; Bronchiectasis with or without elevated sweat chloride 2 613021
Renal tubulopathies v1.53 REN Eleanor Williams Phenotypes for gene: REN were changed from to Hyperuricemic nephropathy, familial juvenile 2, 613092; Renal tubular dysgenesis 267430 AR
Renal tubulopathies v1.52 OCRL Eleanor Williams Phenotypes for gene: OCRL were changed from to Dent disease 2, 300555. Lowe syndrome, 309000
Renal tubulopathies v1.51 NR3C2 Eleanor Williams Phenotypes for gene: NR3C2 were changed from to Pseudohypoaldosteronism type I, autosomal dominant, 177735; Hypertension, early-onset, autosomal dominant, with exacerbation in pregnancy, 605115 no inheritance pattern
Renal tubulopathies v1.50 KLHL3 Eleanor Williams Phenotypes for gene: KLHL3 were changed from to Pseudohypoaldosteronism, type IID, 614495
Renal tubulopathies v1.49 KCNJ10 Eleanor Williams Phenotypes for gene: KCNJ10 were changed from to SESAME/EAST syndrome, 612780; Enlarged vestibular aqueduct, digenic, 60079
Renal tubulopathies v1.48 KCNJ1 Eleanor Williams Phenotypes for gene: KCNJ1 were changed from Hypokalaemic alkalosis with hypercalciuria; Type 2 Bartter syndrome; often initial transient hyperkalemia to Hypokalaemic alkalosis with hypercalciuria; Type 2 Bartter syndrome; often initial transient hyperkalemia; Bartter syndrome, type 2, 241200
Renal tubulopathies v1.47 KCNA1 Eleanor Williams Phenotypes for gene: KCNA1 were changed from to Autosomal dominant hypomagnesemia; Episodic ataxia/myokymia syndrome,160120
Renal tubulopathies v1.46 KCNA1 Eleanor Williams Publications for gene: KCNA1 were set to
Renal tubulopathies v1.45 HNF1B Eleanor Williams Phenotypes for gene: HNF1B were changed from to Renal cysts and diabetes syndrome, 137920; Diabetes mellitus, noninsulin-dependent, 125853
Renal tubulopathies v1.44 GNA11 Eleanor Williams Phenotypes for gene: GNA11 were changed from to Hypocalcemia, autosomal dominant 2 615361
Renal tubulopathies v1.43 FXYD2 Eleanor Williams Phenotypes for gene: FXYD2 were changed from to Hypomagnesemia 2, renal, 154020
Renal tubulopathies v1.42 EHHADH Eleanor Williams Phenotypes for gene: EHHADH were changed from metabolic acidosis, glucosuria, phosphaturia, aminoaciduria, and proteinuria to metabolic acidosis, glucosuria, phosphaturia, aminoaciduria, and proteinuria; ?Fanconi renotubular syndrome 3, 605615
Renal tubulopathies v1.41 EGF Eleanor Williams Phenotypes for gene: EGF were changed from to Hypomagnesemia 4, renal, 611718
Renal tubulopathies v1.40 EGF Eleanor Williams Publications for gene: EGF were set to
Renal tubulopathies v1.39 CYP24A1 Eleanor Williams Phenotypes for gene: CYP24A1 were changed from to Hypercalcemia, infantile, 1 143880
Renal tubulopathies v1.38 CUL3 Eleanor Williams Phenotypes for gene: CUL3 were changed from to Pseudohypoaldosteronism, type IIE, 214496
Renal tubulopathies v1.37 CTNS Eleanor Williams Phenotypes for gene: CTNS were changed from Cystinosis, atypical nephropathic 219800; Cystinosis, late-onset juvenile or adolescent nephropathic 219900; Cystinosis, nephropathic 219800 to Cystinosis, atypical nephropathic 219800; Cystinosis, late-onset juvenile or adolescent nephropathic 219900; Cystinosis, nephropathic 219800; Cystinosis, ocular nonnephropathic 219750
Renal tubulopathies v1.36 CLDN19 Eleanor Williams Phenotypes for gene: CLDN19 were changed from to Hypomagnesemia 5, renal, with ocular involvement, 248190
Renal tubulopathies v1.35 CLDN16 Eleanor Williams Phenotypes for gene: CLDN16 were changed from to Hypomagnesemia 3, renal 248250
Renal tubulopathies v1.34 CLCNKB Eleanor Williams Phenotypes for gene: CLCNKB were changed from Hypokalaemic alkalosis with hypomagnesaemia & hypocalciuria to Hypokalaemic alkalosis with hypomagnesaemia & hypocalciuria; Bartter syndrome, type 3, 607394
Renal tubulopathies v1.33 CLCNKA Eleanor Williams Phenotypes for gene: CLCNKA were changed from to Bartter syndrome, type 4b, digenic 613090
Renal tubulopathies v1.32 CLCNKA Eleanor Williams Publications for gene: CLCNKA were set to
Renal tubulopathies v1.31 CLCN5 Eleanor Williams Phenotypes for gene: CLCN5 were changed from Dent disease, MIM 300009. Hypophosphatemic rickets, 300554. Nephrolithiasis, type I, 310468. Proteinuria, low molecular weight, with hypercalciuric nephrocalcinosis, 308990 to Dent disease, 300009. Hypophosphatemic rickets, 300554. Nephrolithiasis, type I, 310468. Proteinuria, low molecular weight, with hypercalciuric nephrocalcinosis, 308990
Renal tubulopathies v1.30 CLCN5 Eleanor Williams Phenotypes for gene: CLCN5 were changed from to Dent disease, MIM 300009. Hypophosphatemic rickets, 300554. Nephrolithiasis, type I, 310468. Proteinuria, low molecular weight, with hypercalciuric nephrocalcinosis, 308990
Renal tubulopathies v1.29 CASR Eleanor Williams Phenotypes for gene: CASR were changed from to Hypocalcemia, autosomal dominant, (with Bartter syndrome), 601198; Hypocalciuric hypercalcemia, type I, 145980; Hyperparathyroidism, neonatal, 239200
Renal tubulopathies v1.28 AVPR2 Eleanor Williams Phenotypes for gene: AVPR2 were changed from Diabetes insipidus, nephrogenic, 304800; Nephrogenic Diabetes Insipidus; Diabetes Insipidus, Nephrogenic, X-Linked; nephrogenic diabetes insipidus (commonest cause, affected females also reported often with a milder and later presentation) to Diabetes insipidus, nephrogenic, 304800; Nephrogenic Diabetes Insipidus; Diabetes Insipidus, Nephrogenic, X-Linked; nephrogenic diabetes insipidus (commonest cause, affected females also reported often with a milder and later presentation); Nephrogenic syndrome of inappropriate antidiuresis, 300539
Renal tubulopathies v1.27 ATP6V0A4 Eleanor Williams Phenotypes for gene: ATP6V0A4 were changed from Distal Renal Tubular Acidosis, Recessive; Renal tubular acidosis, distal, autosomal recessive, 602722; Distal renal tubular acidosis to Distal Renal Tubular Acidosis, Recessive; Renal tubular acidosis, distal, autosomal recessive, 602722; Distal renal tubular acidosis; Autosomal recessive distal renal tubular acidosis
Renal tubulopathies v1.26 AQP2 Eleanor Williams Phenotypes for gene: AQP2 were changed from Diabetes insipidus, nephrogenic, 125800 to Diabetes insipidus, nephrogenic, 125800; Nephrogenic diabetes insipidus
Renal tubulopathies v1.25 AP2S1 Eleanor Williams Phenotypes for gene: AP2S1 were changed from to Familial hypocalciuric hypercalcemia type III 600740
Renal tubulopathies v1.24 ABCG2 Eleanor Williams Phenotypes for gene: ABCG2 were changed from to Serum uric acid concentration and susceptibility to gout, 138900
Renal tubulopathies v1.23 ABCG2 Eleanor Williams Mode of inheritance for gene: ABCG2 was changed from to Unknown
Haematuria v1.28 NPHS2 Eleanor Williams Phenotypes for gene: NPHS2 were changed from Hematuria, Benign Familial; Alport Syndrome, X-Linked; Alport Syndrome, Autosomal Recessive; Alport Syndrome, Autosomal Dominant; Nephrotic Syndrome, Type 2 to Hematuria, Benign Familial; Alport Syndrome, X-Linked; Alport Syndrome, Autosomal Recessive; Alport Syndrome, Autosomal Dominant; Nephrotic Syndrome, Type 2; ?Modifier of COL4A variants
Haematuria v1.27 NPHS2 Eleanor Williams Publications for gene: NPHS2 were set to
Haematuria v1.26 MYH9 Eleanor Williams Phenotypes for gene: MYH9 were changed from Macrothrombocytopaenia; leukocyte inclusion bodies; sensorineural deafness; proteinuria; haematuria; cataracts; renal failure to Macrothrombocytopaenia; leukocyte inclusion bodies; sensorineural deafness; proteinuria; haematuria; cataracts; renal failure; Epstein syndrome, 153650; Fechtner syndrome, 153640
Haematuria v1.25 MYH9 Eleanor Williams Publications for gene: MYH9 were set to 10973259
Haematuria v1.24 COL4A4 Eleanor Williams Publications for gene: COL4A4 were set to 17942953
Haematuria v1.23 COL4A3 Eleanor Williams Publications for gene: COL4A3 were set to 17942953
Haematuria v1.22 COL4A1 Eleanor Williams Publications for gene: COL4A1 were set to 18160688; 20818663; 27190376; 26839400; 26260163; 28717939
Paediatric disorders - additional genes v0.9 TRAP1 Rebecca Foulger commented on gene: TRAP1
Paediatric disorders - additional genes v0.9 CDX1 Rebecca Foulger commented on gene: CDX1
Paediatric disorders - additional genes v0.7 CDX1 Rebecca Foulger gene: CDX1 was added
gene: CDX1 was added to Paediatric disorders - additional genes. Sources: Expert Review Green
Mode of inheritance for gene: CDX1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CDX1 were set to 23329892; 27042391
Phenotypes for gene: CDX1 were set to anorectal malformation
Paediatric disorders - additional genes v0.7 TRAP1 Rebecca Foulger gene: TRAP1 was added
gene: TRAP1 was added to Paediatric disorders - additional genes. Sources: Expert Review Green
Mode of inheritance for gene: TRAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRAP1 were set to PMID: 24152966 - recessive mutations reported in 2 families with CAKUT, and 3 families with VACTERL.
Phenotypes for gene: TRAP1 were set to CAKUT; VACTERL
Hereditary neuropathy v1.320 PTEN Louise Daugherty Deleted their comment
Hereditary neuropathy v1.320 PPOX Louise Daugherty Deleted their comment
Hereditary neuropathy v1.320 POLR3A Louise Daugherty Deleted their comment
Hereditary neuropathy v1.320 PNKP Louise Daugherty Deleted their comment
Hereditary neuropathy v1.320 PMM2 Louise Daugherty Deleted their comment
Rare multisystem ciliopathy disorders v1.91 IFT43 Rebecca Foulger Classified gene: IFT43 as Green List (high evidence)
Rare multisystem ciliopathy disorders v1.91 IFT43 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green based on two Green reviews from Penny Clouston and Zornitza Stark. Sufficient cases in the literature to support inclusion on the Ciliopathy panel.
Rare multisystem ciliopathy disorders v1.91 IFT43 Rebecca Foulger Gene: ift43 has been classified as Green List (High Evidence).
Rare multisystem ciliopathy disorders v1.90 IFT43 Rebecca Foulger Phenotypes for gene: IFT43 were changed from Cranioectodermal dysplasia 3, 614099 to Cranioectodermal dysplasia 3, 614099; Short-rib polydactyly syndrome; Sensenbrenner syndrome
Rare multisystem ciliopathy disorders v1.89 IFT43 Rebecca Foulger Publications for gene: IFT43 were set to 21378380; 22791528; 26892345 - a case report of a girl with mild intellectual disability, skeletal anomalies, congenital heart defect, myopia, and facial dysmorphisms identified a 4q24.2q24.3 microdeletion containing the IFT43 gene could provide some additional evidence: "immunocytochemistry showed increased accumulation of IFT-B proteins at the ciliary tip in patient-derived fibroblasts compared to control cells, demonstrating defective retrograde ciliary transport. This could suggest a ciliary defect in the pathogenesis of this disorder."; 24027799 (GeneReviews)
Rare multisystem ciliopathy disorders v1.88 IFT43 Rebecca Foulger commented on gene: IFT43
Rare multisystem ciliopathy disorders v1.88 GLIS2 Rebecca Foulger commented on gene: GLIS2: Kept rating as Amber following Red reviews from Penny Clouston and Andrea Nemeth- insufficient evidence for inclusion of GLIS2 on this Ciliopathy panel.
Rare multisystem ciliopathy disorders v1.88 GLIS2 Rebecca Foulger Tag watchlist tag was added to gene: GLIS2.
Rare multisystem ciliopathy disorders v1.88 GLIS2 Rebecca Foulger Phenotypes for gene: GLIS2 were changed from Nephronophthisis 7, 611498; Nephronophthisis to Nephronophthisis 7, 611498; Nephronophthisis; NPHP
Rare multisystem ciliopathy disorders v1.87 GLIS2 Rebecca Foulger Publications for gene: GLIS2 were set to 26374130 (functional study); 23559409; 18227149 Glis2 mutant (Glis2(mut)) mice exhibit significantly shorter life spans compared to wild-type (WT) mice, due to the development of progressive chronic kidney disease with features resembling nephronophthisis; 17618285 - Canadian Oji-Cree kindred
Rare multisystem ciliopathy disorders v1.86 GLIS2 Rebecca Foulger commented on gene: GLIS2
Early onset or syndromic epilepsy v1.57 KMT5B Eleanor Williams gene: KMT5B was added
gene: KMT5B was added to Genetic epilepsy syndromes. Sources: Literature
Mode of inheritance for gene: KMT5B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KMT5B were set to 29276005
Phenotypes for gene: KMT5B were set to Mental retardation, autosomal dominant 51, 617788
Review for gene: KMT5B was set to RED
Added comment: KMT5B is associated with Mental retardation, autosomal dominant 51 (#617788) in OMIM and KMT5B syndrome on Gene2phenotype. This syndrome has intellectual disability and overgrowth listed as phenotypes.

PMID: 29276005 - Faundes et al 2018 - looked at patients from the Deciphering Developmental Disorders (DDD) study that high-quality-call genetic variants in methyltransferases (KMTs) and demethylases (KDMs) not yet firmly associated with DDs. 4 patients identified with either variants or deletions in KMT5B. 2 had nonsense variants, 2 had deletions encompassing KMT5B (399 kb and 839 kb). All had mild to severe intellectual disability. 2 (1 with nonsense variant, 1 with a deletion) also had seizures.
Sources: Literature
Early onset or syndromic epilepsy v1.57 KMT5B Eleanor Williams gene: KMT5B was added
gene: KMT5B was added to Genetic epilepsy syndromes. Sources: Literature
Mode of inheritance for gene: KMT5B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KMT5B were set to 29276005
Phenotypes for gene: KMT5B were set to Mental retardation, autosomal dominant 51, 617788
Review for gene: KMT5B was set to RED
Added comment: KMT5B is associated with Mental retardation, autosomal dominant 51 (#617788) in OMIM and KMT5B syndrome on Gene2phenotype. This syndrome has intellectual disability and overgrowth listed as phenotypes.

PMID: 29276005 - Faundes et al 2018 - looked at patients from the Deciphering Developmental Disorders (DDD) study that high-quality-call genetic variants in methyltransferases (KMTs) and demethylases (KDMs) not yet firmly associated with DDs. 4 patients identified with either variants or deletions in KMT5B. 2 had nonsense variants, 2 had deletions encompassing KMT5B (399 kb and 839 kb). All had mild to severe intellectual disability. 2 (1 with nonsense variant, 1 with a deletion) also had seizures.
Sources: Literature
Intellectual disability v2.874 KMT5B Eleanor Williams Phenotypes for gene: KMT5B were changed from Mental retardation, autosomal dominant 51 to Mental retardation, autosomal dominant 51, 617788
Intellectual disability v2.873 KMT5B Eleanor Williams Classified gene: KMT5B as Green List (high evidence)
Intellectual disability v2.873 KMT5B Eleanor Williams Added comment: Comment on list classification: Sufficient cases of patients with ID to rate green
Intellectual disability v2.873 KMT5B Eleanor Williams Gene: kmt5b has been classified as Green List (High Evidence).
Intellectual disability v2.872 KMT5B Eleanor Williams Classified gene: KMT5B as Green List (high evidence)
Intellectual disability v2.872 KMT5B Eleanor Williams Added comment: Comment on list classification: Sufficient cases of patients with ID to rate green
Intellectual disability v2.872 KMT5B Eleanor Williams Gene: kmt5b has been classified as Green List (High Evidence).
Intellectual disability v2.871 KMT5B Eleanor Williams Classified gene: KMT5B as Green List (high evidence)
Intellectual disability v2.871 KMT5B Eleanor Williams Added comment: Comment on list classification: Sufficient cases of patients with ID to rate green
Intellectual disability v2.871 KMT5B Eleanor Williams Gene: kmt5b has been classified as Green List (High Evidence).
Intellectual disability v2.870 KMT5B Eleanor Williams commented on gene: KMT5B
Intellectual disability v2.870 SEPSECS Ivone Leong Classified gene: SEPSECS as Green List (high evidence)
Intellectual disability v2.870 SEPSECS Ivone Leong Added comment: Comment on list classification: Promoted from red to green based on evidence provided by previous review.
Intellectual disability v2.870 SEPSECS Ivone Leong Gene: sepsecs has been classified as Green List (High Evidence).
Intellectual disability v2.869 SEPSECS Ivone Leong gene: SEPSECS was added
gene: SEPSECS was added to Intellectual disability. Sources: Expert Review
Mode of inheritance for gene: SEPSECS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SEPSECS were set to 26805434; 29464431; 28133863; 26115735; 27576344; 26888482
Phenotypes for gene: SEPSECS were set to Pontocerebellar hypoplasia type 2D, 613811
Review for gene: SEPSECS was set to GREEN
Added comment: Submitted on behalf of Professor Sian Ellard (South West Genomic Laboratory Hub), who has a patient with compound heterozygous SEPSECS variants identified through a gene-agnostic trio analysis of the 100,000 Genome Project data.

SEPSECS is associated with a phenotype in OMIM and Gene2Phenotype and it is a green gene in the Genetic epilepsy syndromes panel (v1.56). There are >3 unrelated cases (PMID: 26805434;29464431;28133863;26115735;26888482) of different missense and frameshift variants in this gene associated with patients who are diagnosed with Pontocerebellar hypoplasia type 2D. All patients have profound intellectual disability and some have developmental delay. PMID: 27576344 is a study that looked at the structural porperties of some of the disease-associated variants and found showed that the variants cause reduced stability and increased propensity towards misfolding of the protein.
Sources: Expert Review
Mitochondrial disorders v1.387 PYCR1 Ellen McDonagh Classified gene: PYCR1 as Red List (low evidence)
Mitochondrial disorders v1.387 PYCR1 Ellen McDonagh Added comment: Comment on list classification: Demoted from Green to Red due to review from the GMS mitochondrial specialist group review, submitted by Carl Fratter on 11th June 2019, and agreement with Anna De Burca and Helen Brittain in the Genomics England Clinical Team on 14th June 2019. This is not considered a mitochondrial disease and is covered as Green by other gene panels.
Mitochondrial disorders v1.387 PYCR1 Ellen McDonagh Gene: pycr1 has been classified as Red List (Low Evidence).
Mitochondrial disorders v1.386 SLC25A22 Ellen McDonagh Classified gene: SLC25A22 as Red List (low evidence)
Mitochondrial disorders v1.386 SLC25A22 Ellen McDonagh Gene: slc25a22 has been classified as Red List (Low Evidence).
Mitochondrial disorders v1.385 SLC25A22 Ellen McDonagh Classified gene: SLC25A22 as Amber List (moderate evidence)
Mitochondrial disorders v1.385 SLC25A22 Ellen McDonagh Added comment: Comment on list classification: Demoted from Green to Amber due to review from the GMS mitochondrial specialist group review, submitted by Carl Fratter, and agreement with Anna De Burca and Helen Brittain in the Genomics England Clinical Team.
Mitochondrial disorders v1.385 SLC25A22 Ellen McDonagh Gene: slc25a22 has been classified as Amber List (Moderate Evidence).
Intellectual disability v2.868 PUF60 Leanne Baxter reviewed gene: PUF60: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Syndromic intellectual disability, prenatal onset growth failure, bifid uvula, retinal atrophy, congenital microcephaly, short stature, long fingers, deviation of toes, short thorax; Mode of inheritance: None
RASopathies v1.42 PTPN11 Sarah Leigh Phenotypes for gene: PTPN11 were changed from LEOPARD syndrome; LEOPARD syndrome 1; Noonan syndrome; Noonan syndrome 1 to LEOPARD syndrome 1 151100; Noonan syndrome 1 163950
RASopathies v1.41 NRAS Sarah Leigh Phenotypes for gene: NRAS were changed from Noonan syndrome; Noonan syndrome 6; Cardio-Facio-cutanenous syndrome; CFC Syndrome to Noonan syndrome 6 613224; Cardio-Facio-cutanenous syndrome; CFC Syndrome
RASopathies v1.40 NRAS Sarah Leigh Publications for gene: NRAS were set to PMID: 19966803; 19775298
RASopathies v1.39 NF1 Sarah Leigh Publications for gene: NF1 were set to PMID: 16380919; 19845691; 12707950
RASopathies v1.38 NF1 Sarah Leigh Phenotypes for gene: NF1 were changed from Neurofibromatosis-Noonan syndrome 601321 to Neurofibromatosis-Noonan syndrome 601321; Neurofibromatosis, type 1 162200
RASopathies v1.37 NF1 Sarah Leigh Phenotypes for gene: NF1 were changed from Neurofibromatosis-Noonan Syndrome; Neurofibromatosis Noonan syndrome; Noonan syndrome; Neurofibromatosis syndrome 1 to Neurofibromatosis-Noonan syndrome 601321
RASopathies v1.36 MAP2K2 Sarah Leigh Publications for gene: MAP2K2 were set to PMID: 21396583; 23379592
RASopathies v1.35 MAP2K2 Sarah Leigh Phenotypes for gene: MAP2K2 were changed from Cardiofaciocutaneous syndrome 4; Cardio-Facio-Cutaneous syndrome type 4; Cardiofaciocutaneous Syndrome; Cardio-Facio-Cutaneous syndrome; CFC syndrome to Cardiofaciocutaneous syndrome 4 615280
RASopathies v1.34 LZTR1 Sarah Leigh Phenotypes for gene: LZTR1 were changed from Noonan syndrome 10; Prenatal hydrops; increased nuchal translucency; cardiac findings to Noonan syndrome 10 616564; Schwannomatosis-2, susceptibility to 615670
RASopathies v1.33 KRAS Sarah Leigh Phenotypes for gene: KRAS were changed from Noonan syndrome 3; Noonan syndrome; Cardiofaciocutaneous syndrome 2; Cardiofaciocutaneous Syndrome; Cardio-Facio-Cutaneous syndrome; CFC syndrome to Noonan syndrome 3 609942; Cardiofaciocutaneous syndrome 2 615278
RASopathies v1.32 HRAS Sarah Leigh Publications for gene: HRAS were set to PMID: 16170316; 16969868; 16443854; 21396583
RASopathies v1.31 CBL Sarah Leigh Phenotypes for gene: CBL were changed from Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia to Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia 613563
RASopathies v1.30 CBL Sarah Leigh Publications for gene: CBL were set to PMID: 20619386; 20543203; 19571318
RASopathies v1.29 BRAF Sarah Leigh Phenotypes for gene: BRAF were changed from LEOPARD Syndrome; Noonan Syndrome; Cardiofaciocutaneous Syndrome; LEOPARD syndrome 3; Cardio-facio-cutaneous syndrome to LEOPARD syndrome 3 613707; Cardiofaciocutaneous syndrome 115150; Noonan syndrome 7 613706
RASopathies v1.28 BRAF Sarah Leigh Publications for gene: BRAF were set to PMID: 19206169; 21396583; PMID: 19206169; 21396583; PMID: 19206169; 21396583; PMID: 19206169; 21396583
Intellectual disability v2.868 KMT2E Eleanor Williams Phenotypes for gene: KMT2E were changed from to Global developmental delay; Intellectual disability; Autism; Seizures; Abnormality of skull size
Intellectual disability v2.867 KMT2E Eleanor Williams Classified gene: KMT2E as Green List (high evidence)
Intellectual disability v2.867 KMT2E Eleanor Williams Added comment: Comment on list classification: Sufficient cases with ID to rate green.
Intellectual disability v2.867 KMT2E Eleanor Williams Gene: kmt2e has been classified as Green List (High Evidence).
Intellectual disability v2.866 KMT2E Eleanor Williams Publications for gene: KMT2E were set to 31079897
Intellectual disability v2.865 KMT2E Eleanor Williams Publications for gene: KMT2E were set to
Intellectual disability v2.864 KMT2E Eleanor Williams commented on gene: KMT2E
Intellectual disability v2.864 KMT2E Eleanor Williams Mode of inheritance for gene: KMT2E was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy v1.56 KMT2E Eleanor Williams Classified gene: KMT2E as Green List (high evidence)
Early onset or syndromic epilepsy v1.56 KMT2E Eleanor Williams Added comment: Comment on list classification: Sufficient cases to rate green.
Early onset or syndromic epilepsy v1.56 KMT2E Eleanor Williams Gene: kmt2e has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v1.55 KMT2E Eleanor Williams commented on gene: KMT2E: Not associated with any phenotype in OMIM. Confirmed association with Intellectual disability in Gene2Phenotype (monoallelic)

PMID: 31079897 O'Donnell-Luria et al 2019 - report on additional 35 individuals with heterozygous variants in KMT2E and 3 previously reported males. New cases were ascertained from GeneMatcher through the Matchmaker Exchange Network and MyGene2. 34 individuals from 32 families were found to have single-nucleotide or indel variants in KMT2E, and four additional individuals had copy-number variants encompassing KMT2E. 11 unrelated individuals had epilepsy - 3 had microdeletions, 4 missense variants, 2 frameshift, 1 nonsense and 1 a variant affecting a splice site.

Sufficient cases with likely disease-causing variants to rate as green.
Early onset or syndromic epilepsy v1.55 KMT2E Eleanor Williams Added comment: Comment on publications: URL was to the paper in Bioxriv. Paper is now in Am J Hum Genet
Early onset or syndromic epilepsy v1.55 KMT2E Eleanor Williams Publications for gene: KMT2E were set to https://doi.org/10.1101/566091
Clefting v1.37 ALX1 Eleanor Williams Phenotypes for gene: ALX1 were changed from to ?Frontonasal dysplasia 3, 613456
Clefting v1.36 ALX1 Eleanor Williams Publications for gene: ALX1 were set to
Monogenic hearing loss v1.114 GJB6 Eleanor Williams Classified gene: GJB6 as Amber List (moderate evidence)
Monogenic hearing loss v1.114 GJB6 Eleanor Williams Added comment: Comment on list classification: After consideration by the Genomics England rare disease clinical team it was decided to rate this gene Amber until there is further evidence for the role of SNVs in this gene causing hearing loss.
Monogenic hearing loss v1.114 GJB6 Eleanor Williams Gene: gjb6 has been classified as Amber List (Moderate Evidence).
Intellectual disability v2.863 ALKBH8 Catherine Snow Publications for gene: ALKBH8 were set to
Unexplained young onset end-stage renal disease v0.16 GLA Eleanor Williams commented on gene: GLA: GLA is associated with Fabry disease (#301500) in OMIM


PMID: 28006774 - Turkmen et al 2016 - 3 out of 313 chronic kidney disease patients not receiving renal replacement therapy (0.95%) were diagnosed of Fabry disease by GLA gene mutation analysis. The age of the patients and their family members with Fabry disease ( total number =11) was 41.3 +/- 14.5.

PMID: 15861341 - Cybulla et al 2005 - describe a family presenting with chronic renal failure and proteinuria in which classic skin and neurological features were absent and the diagnosis of Fabry disease was difficult and not established until a second family member developed renal abnormalities. The index patient was 35 years old. Analysis of the alpha-GLA gene showed the mutation E66K. The mutation also was found in another asymptomatic 30-year-old brother who also had chronic renal failure and proteinuria, but normal extrarenal findings. Mutation carriers also included the mother, a sister (both without abnormalities), and a nephew (with episodic pains in his feet).

PMID: 15100373 - Kotanko et al 2004 - Nationwide screening of Anderson-Fabry disease among dialysis patients in Austria. Individuals with decreased leukocyte AGAL activity were subjected to mutation testing in the GLA gene, Genetic testing revealed mutations associated with Fabry disease in all four men with severely decreased AGAL activity resulting in a prevalence of 0.161% for the entire study population. Age at start of dialysis ranged from 27 to 53.
Hereditary neuropathy v1.320 FXN_GAA Louise Daugherty reviewed STR: FXN_GAA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Monogenic hearing loss v1.113 HGF Eleanor Williams Tag watchlist tag was added to gene: HGF.
Monogenic hearing loss v1.113 HGF Eleanor Williams Classified gene: HGF as Amber List (moderate evidence)
Monogenic hearing loss v1.113 HGF Eleanor Williams Added comment: Comment on list classification: After review with the GMS hearing specialist test group in a Webex on 2019-02-13 and consultation with the Genomics England clinical team it was decided to rate this gene Amber and add a watchlist tag.
Monogenic hearing loss v1.113 HGF Eleanor Williams Gene: hgf has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v1.112 SLC17A8 Eleanor Williams Classified gene: SLC17A8 as Green List (high evidence)
Monogenic hearing loss v1.112 SLC17A8 Eleanor Williams Added comment: Comment on list classification: Upgrading from red to green based on new evidence added.
Monogenic hearing loss v1.112 SLC17A8 Eleanor Williams Gene: slc17a8 has been classified as Green List (High Evidence).
Monogenic hearing loss v1.111 DIAPH1 Eleanor Williams Classified gene: DIAPH1 as Green List (high evidence)
Monogenic hearing loss v1.111 DIAPH1 Eleanor Williams Added comment: Comment on list classification: Upgrading from red to green after discussion with the GMS musculoskeletal specialist test group in a Webex on 2019-05-13 and consultation with the Genomics England clinical team
Monogenic hearing loss v1.111 DIAPH1 Eleanor Williams Gene: diaph1 has been classified as Green List (High Evidence).
Monogenic hearing loss v1.110 SIX5 Eleanor Williams Classified gene: SIX5 as Amber List (moderate evidence)
Monogenic hearing loss v1.110 SIX5 Eleanor Williams Added comment: Comment on list classification: Upgrading from red to amber. Amber rating agreed at the GMS hearing specialist test group Webex on 2019-02-13
Monogenic hearing loss v1.110 SIX5 Eleanor Williams Gene: six5 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy v1.320 NOP56_GGCCTG Louise Daugherty Source Expert list was removed from STR: NOP56_GGCCTG.
Source Expert Review was added to STR: NOP56_GGCCTG.
Hereditary neuropathy v1.319 FMR1_CGG Louise Daugherty Source Expert list was removed from STR: FMR1_CGG.
Source Expert Review was added to STR: FMR1_CGG.
Hereditary neuropathy v1.318 ATXN7_CAG Louise Daugherty Source Expert list was removed from STR: ATXN7_CAG.
Source Expert Review was added to STR: ATXN7_CAG.
Hereditary neuropathy v1.317 AR_CAG Louise Daugherty Source Expert list was removed from STR: AR_CAG.
Source Expert Review was added to STR: AR_CAG.
Hereditary neuropathy v1.316 PPP2R2B_CAG Louise Daugherty Source Expert list was removed from STR: PPP2R2B_CAG.
Hereditary neuropathy v1.315 PPP2R2B_CAG Louise Daugherty Source Expert Review was added to STR: PPP2R2B_CAG.
DDG2P v1.66 FMR1 Rebecca Foulger Added comment: Comment on mode of inheritance: DDG2P mode of inheritance is hemizygous for FRAGILE X SYNDROME (confirmed); hemizygous for FRAGILE X TREMOR/ATAXIA SYNDROME (both DD and IF); x-linked dominant for PREMATURE OVARIAN FAILURE SYNDROME TYPE 1 (both DD and IF).
DDG2P v1.66 FMR1 Rebecca Foulger Mode of inheritance for gene: FMR1 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)
DDG2P v1.65 EFNB1 Rebecca Foulger Added comment: Comment on mode of inheritance: Changed Mode of inheritance from 'x-linked over-dominance' to standardised PanelApp term for X-linked dominant; this matches the MOI of EFNB1 on other PanelApp panels.
DDG2P v1.65 EFNB1 Rebecca Foulger Mode of inheritance for gene: EFNB1 was changed from x-linked over-dominance to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
DDG2P v1.64 ADAR Rebecca Foulger Added comment: Comment on mode of inheritance: DDG2P MOI is biallelic for SPONDYLOEPIMETAPHYSEAL DYSPLASIA AGGRECAN TYPE; monoallelic for SPONDYLOEPIPHYSEAL DYSPLASIA TYPE KIMBERLEY. Both disorders have a confirmed Disease confidence rating.
DDG2P v1.64 ADAR Rebecca Foulger Mode of inheritance for gene: ADAR was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
DDG2P v1.63 ADAR Rebecca Foulger Added comment: Comment on mode of inheritance: DDG2P MOI is both monoallelic and biallelic for AICARDI-GOUTIERES SYNDROME ASSOCIATED WITH A TYPE I INTERFERON SIGNATURE; monoallelic for DYSCHROMATOSIS SYMMETRICA HEREDITARIA 1. Both disorders have a confirmed Disease confidence rating.
DDG2P v1.63 ADAR Rebecca Foulger Mode of inheritance for gene: ADAR was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
DDG2P v1.62 ALDH18A1 Rebecca Foulger Added comment: Comment on mode of inheritance: DDG2P MOI is monoallelic for CUTIS LAXA, AUTOSOMAL DOMINANT 3;biallelic for MENTAL RETARDATION-JOINT HYPERMOBILITY-SKIN LAXITY WITH OR WITHOUT METABOLIC ABNORMALITIES; monoallelic for SPASTIC PARAPLEGIA 9, AUTOSOMAL DOMINANT. All disorders have a confirmed Disease confidence rating.
DDG2P v1.62 ALDH18A1 Rebecca Foulger Mode of inheritance for gene: ALDH18A1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary neuropathy v1.314 ATXN7_CAG Louise Daugherty Classified STR: ATXN7_CAG as Amber List (moderate evidence)
Hereditary neuropathy v1.314 ATXN7_CAG Louise Daugherty Str: atxn7_cag has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy v1.313 ATXN7_CAG Louise Daugherty STR: ATXN7_CAG was added
STR: ATXN7_CAG was added to Hereditary neuropathy. Sources: Expert list
STR tags were added to STR: ATXN7_CAG.
Mode of inheritance for STR: ATXN7_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: ATXN7_CAG were set to 25614072
Phenotypes for STR: ATXN7_CAG were set to Spinocerebellar ataxia 7 164500; Adult onset, cerebellar ataxia, pigmentary macular degeneration, sensory-motor axonal neuropathy
Review for STR: ATXN7_CAG was set to GREEN
Added comment: New Green STR submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group. This STR has been rated Amber until further discussion with the Neurology Test Group on 21st June 2019- although appropriate to have on this panel, they can be more late-onset, this panel is used for children so needs further discussion with the GLHs and Genomics England Clinical team before upgrading to Green
Sources: Expert list
Hereditary neuropathy v1.312 FMR1_CGG Louise Daugherty Classified STR: FMR1_CGG as Amber List (moderate evidence)
Hereditary neuropathy v1.312 FMR1_CGG Louise Daugherty Str: fmr1_cgg has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy v1.311 FMR1_CGG Louise Daugherty STR: FMR1_CGG was added
STR: FMR1_CGG was added to Hereditary neuropathy. Sources: Expert list
currently-ngs-unreportable, STR tags were added to STR: FMR1_CGG.
Mode of inheritance for STR: FMR1_CGG 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 STR: FMR1_CGG were set to 26212380
Phenotypes for STR: FMR1_CGG were set to Fragile X syndrome 300624; Late onset tremor, ataxia, parkinsonism, sensory axonal neuropathy, middle cerebellar peduncle changes on MRI
Review for STR: FMR1_CGG was set to GREEN
Added comment: New Green STR submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group. This STR has been rated Amber until further discussion with the Neurology Test Group on 21st June 2019- although appropriate to have on this panel, they can be more late-onset, this panel is used for children so needs further discussion with the GLHs and Genomics England Clinical team before upgrading to Green
Sources: Expert list
Hereditary neuropathy v1.310 NOP56_GGCCTG Louise Daugherty Classified STR: NOP56_GGCCTG as Amber List (moderate evidence)
Hereditary neuropathy v1.310 NOP56_GGCCTG Louise Daugherty Str: nop56_ggcctg has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy v1.309 NOP56_GGCCTG BRIDGE consortium Deleted their review
Hereditary neuropathy v1.309 NOP56_GGCCTG BRIDGE consortium reviewed STR: NOP56_GGCCTG: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Hereditary neuropathy v1.309 NOP56_GGCCTGTT BRIDGE consortium STR: NOP56_GGCCTGTT was added
STR: NOP56_GGCCTGTT was added to Hereditary neuropathy. Sources: Expert list
Mode of inheritance for STR: NOP56_GGCCTGTT was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Review for STR: NOP56_GGCCTGTT was set to AMBER
Added comment: test
Sources: Expert list
Hereditary neuropathy v1.309 NOP56_GGCCTG Louise Daugherty STR: NOP56_GGCCTG was added
STR: NOP56_GGCCTG was added to Hereditary neuropathy. Sources: Expert list
STR tags were added to STR: NOP56_GGCCTG.
Mode of inheritance for STR: NOP56_GGCCTG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for STR: NOP56_GGCCTG were set to Spinocerebellar ataxia 36, 614153Late adult onset gait ataxia, tongue atrophy and fasciculation, distal motor neuropathy
Review for STR: NOP56_GGCCTG was set to GREEN
Added comment: New Green STR submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group. This STR has been rated Amber until further discussion with the Neurology Test Group on 21st June 2019- although appropriate to have on this panel, they can be more late-onset, this panel is used for children so needs further discussion with the GLHs and Genomics England Clinical team before upgrading to Green
Sources: Expert list
Hereditary neuropathy v1.308 Louise Daugherty removed STR:FXTS from the panel
Hereditary neuropathy v1.307 FXTS Louise Daugherty STR: FXTS was added
STR: FXTS was added to Hereditary neuropathy. Sources: Expert Review
Mode of inheritance for STR: FXTS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added comment: test
Sources: Expert Review
Hereditary neuropathy v1.306 Louise Daugherty removed STR:FXTS from the panel
Hereditary neuropathy v1.305 PPP2R2B_CAG Louise Daugherty edited their review of STR: PPP2R2B_CAG: Changed rating: GREEN
Hereditary neuropathy v1.305 PPP2R2B_CAG Louise Daugherty Classified STR: PPP2R2B_CAG as Amber List (moderate evidence)
Hereditary neuropathy v1.305 PPP2R2B_CAG Louise Daugherty Added comment: Comment on list classification: New Green STR submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group. This STR has been rated Amber until further discussion with the Neurology Test Group on 21st June 2019- although appropriate to have on this panel, they can be more late-onset, this panel is used for children so needs further discussion with the GLHs and Genomics England Clinical team before upgrading to Green
Hereditary neuropathy v1.305 PPP2R2B_CAG Louise Daugherty Str: ppp2r2b_cag has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy v1.304 PPP2R2B_CAG Louise Daugherty Classified STR: PPP2R2B_CAG as Amber List (moderate evidence)
Hereditary neuropathy v1.304 PPP2R2B_CAG Louise Daugherty Str: ppp2r2b_cag has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy v1.303 PPP2R2B_CAG Louise Daugherty STR: PPP2R2B_CAG was added
STR: PPP2R2B_CAG was added to Hereditary neuropathy. Sources: Expert list
STR tags were added to STR: PPP2R2B_CAG.
Mode of inheritance for STR: PPP2R2B_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: PPP2R2B_CAG were set to 16138911
Phenotypes for STR: PPP2R2B_CAG were set to Spinocerebellar ataxia 12 604326; Adult onset cerebellar ataxia, tremor of head and arms, subclinical sensory-motor axonal neuropathy; neuropathy minor feature
Review for STR: PPP2R2B_CAG was set to AMBER
Added comment: Sources: Expert list
Paediatric motor neuronopathies v1.21 Louise Daugherty removed STR:AR_CAG from the panel
Amyotrophic lateral sclerosis/motor neuron disease v1.27 AR_CAG Louise Daugherty GRCh38 position for AR_CAG was changed from 67545318-67545383 to 67545316-67545383.
Mode of inheritance for STR: AR_CAG 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)
Rating Changed from Green List (high evidence) to Green List (high evidence)
Hereditary neuropathy v1.302 AR_CAG Louise Daugherty GRCh37 position for AR_CAG was changed from - to 66765160-66765225.
GRCh38 position for AR_CAG was changed from 67544622-67730618 to 67545316-67545383.
Normal Number of Repeats for AR_CAG was changed from 36 to 34.
Mode of inheritance for STR: AR_CAG 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)
Clefting v1.35 ALX1 Eleanor Williams commented on gene: ALX1: This gene is provisionally associated with ?Frontonasal dysplasia 3 (#613456) in OMIM.

PMID: 20451171 - Uz et al. (2010) - 2 families presenting with autosomal-recessive frontonasal dysplasia (FND) characterized by bilateral extreme microphthalmia, bilateral oblique facial cleft, complete cleft palate, hypertelorism, wide nasal bridge with hypoplasia of the ala nasi, and low-set, posteriorly rotated ears in two distinct families. In one family they found a three siblings were affected, and CNV analysis of the critical region showed a homozygous 3.7 Mb deletion containing the ALX1 (CART1) gene. In the second family a homozygous donor-splice-site mutation (c.531+1G > A) in the ALX1 gene was found.

PMID: 27324866 - Ullah et al 2017 - report a consanguineous family from Pakistan with four individuals presenting a milder form of Frontonasal dysplasia. Using exome sequencing, a homozygous splice acceptor site variant has been identified in the ALX1 gene. NO CLEFTING REPORTED.
Mitochondrial disorders v1.384 VPS13C Carl Fratter reviewed gene: VPS13C: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Parkinson disease 23, autosomal recessive, early onset, 616840; Mode of inheritance:
Mitochondrial disorders v1.384 TANGO2 Carl Fratter reviewed gene: TANGO2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration, 616878; Mode of inheritance:
Mitochondrial disorders v1.384 STAT2 Carl Fratter reviewed gene: STAT2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Immunodeficiency 44, 616636; Mode of inheritance:
Mitochondrial disorders v1.384 SLC25A22 Carl Fratter reviewed gene: SLC25A22: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Epileptic encephalopathy, early infantile, 3, 609304; Mode of inheritance:
Mitochondrial disorders v1.384 ROBO3 Carl Fratter reviewed gene: ROBO3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Gaze palsy, familial horizontal, with progressive scoliosis, 1, 607313; Mode of inheritance:
Mitochondrial disorders v1.384 PYCR1 Carl Fratter reviewed gene: PYCR1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cutis laxa, autosomal recessive, type IIB, 612940, Cutis laxa, autosomal recessive, type IIIB, 614438; Mode of inheritance:
Mitochondrial disorders v1.384 IER3IP1 Carl Fratter reviewed gene: IER3IP1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Microcephaly, epilepsy, and diabetes syndrome, 614231; Mode of inheritance:
Mitochondrial disorders v1.384 HMGCL Carl Fratter reviewed gene: HMGCL: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: HMG-CoA lyase deficiency, 246450; Mode of inheritance:
Mitochondrial disorders v1.384 GLUD1 Carl Fratter reviewed gene: GLUD1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Hyperinsulinism-hyperammonemia syndrome, 606762; Mode of inheritance:
Mitochondrial disorders v1.384 FXN Carl Fratter reviewed gene: FXN: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Friedreich ataxia, 229300; Mode of inheritance:
Mitochondrial disorders v1.384 DHTKD1 Carl Fratter reviewed gene: DHTKD1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: 2-aminoadipic 2-oxoadipic aciduria, 204750, ?Charcot-Marie-Tooth disease, axonal, type 2Q 615025; Mode of inheritance:
Mitochondrial disorders v1.384 DARS Carl Fratter reviewed gene: DARS: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Hypomyelination with brainstem and spinal cord involvement and leg spasticity, 615281; Mode of inheritance:
Mitochondrial disorders v1.384 CHKB Carl Fratter reviewed gene: CHKB: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Muscular dystrophy, congenital, megaconial type, 602541; Mode of inheritance:
Mitochondrial disorders v1.384 C19orf12 Carl Fratter reviewed gene: C19orf12: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Neurodegeneration with brain iron accumulation 4, 614298, ?Spastic paraplegia 43, autosomal recessive, 615043; Mode of inheritance:
Clefting v1.35 ALX1 Eleanor Williams gene: ALX1 was added
gene: ALX1 was added to Clefting. Sources: Expert list
Mode of inheritance for gene: ALX1 was set to BIALLELIC, autosomal or pseudoautosomal
Review for gene: ALX1 was set to AMBER
Added comment: Gene suggested by Andrew Wilkie, University of Oxford
Sources: Expert list
Hereditary neuropathy v1.301 AR_CAG Louise Daugherty Classified STR: AR_CAG as Amber List (moderate evidence)
Hereditary neuropathy v1.301 AR_CAG Louise Daugherty Added comment: Comment on list classification: New Green STR submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group. This STR has been rated Amber until further discussion with the Neurology Test Group on 21st June 2019- although appropriate to have on this panel, they can be more late-onset, this panel is used for children so needs further discussion with the GLHs and Genomics England Clinical team before upgrading to Green.
Hereditary neuropathy v1.301 AR_CAG Louise Daugherty Str: ar_cag has been classified as Amber List (Moderate Evidence).
DDG2P v1.61 FBN1 Rebecca Foulger Added comment: Comment on mode of inheritance: In DDG2P, MOI is listed as both monoallelic (dominant negative) and biallelic (loss of function) for confirmed MARFAN SYNDROME; monoallelic for confirmed MASS SYNDROME/OVERLAP CONNECTIVE TISSUE DISEASE; monoallelic for confirmed SHPRINTZEN-GOLDBERG CRANIOSYNOSTOSIS SYNDROME.
DDG2P v1.61 FBN1 Rebecca Foulger Mode of inheritance for gene: FBN1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
DDG2P v1.60 GJC2 Rebecca Foulger Added comment: Comment on mode of inheritance: In DDG2P, MOI is listed as biallelic for LEUKODYSTROPHY, HYPOMYELINATING, 2; monoallelic for LYMPHEDEMA, HEREDITARY, IC; monoallelic for SPASTIC PARAPLEGIA, 44. All disorders have a confirmed Disease confidence rating.
DDG2P v1.60 GJC2 Rebecca Foulger Mode of inheritance for gene: GJC2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
DDG2P v1.59 IHH Rebecca Foulger Added comment: Comment on mode of inheritance: In DDG2P, MOI is listed as biallelic for ACROCAPITOFEMORAL DYSPLASIA; confirmed for BRACHYDACTYLY, TYPE A1. Both diseases have a confirmed Disease confidence rating.
DDG2P v1.59 IHH Rebecca Foulger Mode of inheritance for gene: IHH was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
DDG2P v1.58 ITPR1 Rebecca Foulger Added comment: Comment on mode of inheritance: In DDG2P, MOI is listed as both monoallelic (dominant negative) and biallelic (loss of function) for confirmed Gillespie Syndrome.
DDG2P v1.58 ITPR1 Rebecca Foulger Mode of inheritance for gene: ITPR1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
DDG2P v1.57 KIF1A Rebecca Foulger Added comment: Comment on mode of inheritance: DDG2P MOI is listed as monoallelic for MENTAL RETARDATION, AUTOSOMAL DOMINANT 9 (all missense/in frame); biallelic for NEUROPATHY, HEREDITARY SENSORY, TYPE IIC (loss of function).
DDG2P v1.57 KIF1A Rebecca Foulger Mode of inheritance for gene: KIF1A was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Osteogenesis imperfecta v1.50 CASR Eleanor Williams Classified gene: CASR as Green List (high evidence)
Osteogenesis imperfecta v1.50 CASR Eleanor Williams Added comment: Comment on list classification: This gene was discussed in the GMS musculoskeletal specialist test group Webex on 2019-06-04. It was decided that due to further evidence, it should be made green.
Osteogenesis imperfecta v1.50 CASR Eleanor Williams Gene: casr has been classified as Green List (High Evidence).
Osteogenesis imperfecta v1.49 B4GALT7 Eleanor Williams Classified gene: B4GALT7 as Green List (high evidence)
Osteogenesis imperfecta v1.49 B4GALT7 Eleanor Williams Added comment: Comment on list classification: This gene was discussed in the GMS musculoskeletal specialist test group Webex on 2019-06-04. It was decided that due to further evidence, it should be made green.
Osteogenesis imperfecta v1.49 B4GALT7 Eleanor Williams Gene: b4galt7 has been classified as Green List (High Evidence).
DDG2P v1.56 LRP5 Rebecca Foulger Added comment: Comment on mode of inheritance: DDG2P lists MOI as monoallelic for ENDOSTEAL HYPEROSTOSIS WORTH TYPE; monoallelic for HIGH BONE MASS TRAIT; monoallelic for OSTEOPETROSIS AUTOSOMAL DOMINANT TYPE 1; biallelic for OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME; monoallelic for VITREORETINOPATHY EXUDATIVE TYPE 4. All diseases have a confirmed Disease confidence rating.
DDG2P v1.56 LRP5 Rebecca Foulger Mode of inheritance for gene: LRP5 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
DDG2P v1.55 MAB21L2 Rebecca Foulger Added comment: Comment on mode of inheritance: In DDG2P, MICROPHTHALMIA, SYNDROMIC 14 is listed as monoallelic for an activating mutation consequence, and biallelic for a LOF mutation consequence.
DDG2P v1.55 MAB21L2 Rebecca Foulger Mode of inheritance for gene: MAB21L2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
DDG2P v1.54 MMP13 Rebecca Foulger Added comment: Comment on mode of inheritance: In DDG2P, MOI is listed as biallelic for METAPHYSEAL ANADYSPLASIA TYPE 1; monoallelic for SPONDYLOEPIMETAPHYSEAL DYSPLASIA MISSOURI TYPE. Both diseases have a Confirmed Disease Confidence rating.
DDG2P v1.54 MMP13 Rebecca Foulger Mode of inheritance for gene: MMP13 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
DDG2P v1.53 NALCN Rebecca Foulger Added comment: Comment on mode of inheritance: In DDG2P, MOI is listed as monoallelic for CONGENITAL CONTRACTURES OF THE LIMBS AND FACE, HYPOTONIA, AND DEVELOPMENTAL DELAY; biallelic for HYPOTONIA, INFANTILE, WITH PSYCHOMOTOR RETARDATION AND CHARACTERISTIC FACIES; biallelic for SEVERE HYPOTONIA, SPEECH IMPAIRMENT, AND COGNITIVE DELAY. All diseases have a Confirmed Disease Confidence rating.
DDG2P v1.53 NALCN Rebecca Foulger Mode of inheritance for gene: NALCN was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
DDG2P v1.52 PIEZO2 Rebecca Foulger Added comment: Comment on mode of inheritance: In DDG2P, MOI is listed as monoallelic for ARTHROGRYPOSIS, DISTAL, TYPE 3; biallelic for Ataxia, dysmetria, contractures & scoliosis with normal cognition but loss of discriminative touch perception. Both diseases have a confirmed Disease confidence rating.
DDG2P v1.52 PIEZO2 Rebecca Foulger Mode of inheritance for gene: PIEZO2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
DDG2P v1.51 PIK3R1 Rebecca Foulger Added comment: Comment on mode of inheritance: In DDG2P, MOI is listed as biallelic for AGAMMAGLOBULINEMIA 7, AUTOSOMAL RECESSIVE; monoallelic for SHORT SYNDROME. Both syndromes have a Disease confidence rating of 'confirmed'.
DDG2P v1.51 PIK3R1 Rebecca Foulger Mode of inheritance for gene: PIK3R1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
DDG2P v1.50 PTH1R Rebecca Foulger Added comment: Comment on mode of inheritance: In DDG2P, MOI is listed as biallelic for CHONDRODYSPLASIA BLOMSTRAND TYPE; biallelic for EIKEN SKELETAL DYSPLASIA; monoallelic for ANSEN METAPHYSEAL CHONDRODYSPLASIA; monoallelic for PRIMARY FAILURE OF TOOTH ERUPTION. All diseases have a confirmed Disease confidence rating.
DDG2P v1.50 PTH1R Rebecca Foulger Mode of inheritance for gene: PTH1R was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
DDG2P v1.49 FLNA Rebecca Foulger Added comment: Comment on mode of inheritance: DDG2P MOI is listed as hemizygous mosaic for Childhood Interstitial Lung Disease; x-linked dominant for EPILEPTIC ENCEPHALOPATHY; hemizygous for FG SYNDROME TYPE 2; x-linked dominant for MELNICK-NEEDLES SYNDROME; hemizygous for FRONTOMETAPHYSEAL DYSPLASIA; hemizygous for OTOPALATODIGITAL SYNDROME TYPE 1; hemizygous for OTOPALATODIGITAL SYNDROME TYPE 2; hemizygous for TERMINAL OSSEOUS DYSPLASIA; hemizygous for X-LINKED CONGENITAL IDIOPATHIC INTESTINAL PSEUDOOBSTRUCTION. All disorders have a Confirmed Disease confidence rating.
DDG2P v1.49 FLNA Rebecca Foulger Mode of inheritance for gene: FLNA 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)
Osteogenesis imperfecta v1.48 NUDT6 Eleanor Williams Classified gene: NUDT6 as Amber List (moderate evidence)
Osteogenesis imperfecta v1.48 NUDT6 Eleanor Williams Added comment: Comment on list classification: Following discussion in the GMS musculoskeletal specialist test group Webex on 2019-06-04 it was decided to rate this gene amber until there is more evidence for an association.
Osteogenesis imperfecta v1.48 NUDT6 Eleanor Williams Gene: nudt6 has been classified as Amber List (Moderate Evidence).
Osteogenesis imperfecta v1.47 COPB2 Eleanor Williams Classified gene: COPB2 as Amber List (moderate evidence)
Osteogenesis imperfecta v1.47 COPB2 Eleanor Williams Added comment: Comment on list classification: Following discussion in the GMS musculoskeletal specialist test group Webex on 2019-06-04 it was decided to make this gene amber.
Osteogenesis imperfecta v1.47 COPB2 Eleanor Williams Gene: copb2 has been classified as Amber List (Moderate Evidence).
Osteogenesis imperfecta v1.46 NBAS Eleanor Williams Classified gene: NBAS as Green List (high evidence)
Osteogenesis imperfecta v1.46 NBAS Eleanor Williams Added comment: Comment on list classification: Following discussion in the GMS musculoskeletal specialist test group Webex on 2019-06-04 it was decided to make this gene green. 2 cases plus functional data.
Osteogenesis imperfecta v1.46 NBAS Eleanor Williams Gene: nbas has been classified as Green List (High Evidence).
DDG2P v1.48 IKBKG Rebecca Foulger Added comment: Comment on mode of inheritance: DDG2P records an MOI of hemizygous for ECTODERMAL DYSPLASIA ANHIDROTIC WITH IMMUNODEFICIENCY X-LINKED; ECTODERMAL DYSPLASIA ANHIDROTIC WITH IMMUNODEFICIENCY-OSTEOPETROSIS-LYMPHEDEMA; IMMUNODEFICIENCY NEMO-RELATED WITHOUT ANHIDROTIC ECTODERMAL DYSPLASIA; SUSCEPTIBILITY TO X-LINKED FAMILIAL ATYPICAL MICOBACTERIOSIS TYPE 1. DDG2P records an MOI of monoallelic for INCONTINENTIA PIGMENTI 308300.
DDG2P v1.48 IKBKG Rebecca Foulger Mode of inheritance for gene: IKBKG 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)
Osteogenesis imperfecta v1.45 NBAS Eleanor Williams Deleted their comment
Osteogenesis imperfecta v1.45 NBAS Eleanor Williams Classified gene: NBAS as Red List (low evidence)
Osteogenesis imperfecta v1.45 NBAS Eleanor Williams Added comment: Comment on list classification: Following discussion in the GMS musculoskeletal specialist test group Webex on 2019-06-04 it was decided to make this gene green. 2 cases plus functional data.
Osteogenesis imperfecta v1.45 NBAS Eleanor Williams Gene: nbas has been classified as Red List (Low Evidence).
Osteogenesis imperfecta v1.44 NBAS Eleanor Williams Mode of inheritance for gene: NBAS was changed from to BIALLELIC, autosomal or pseudoautosomal
DDG2P v1.47 NSDHL Rebecca Foulger Added comment: Comment on mode of inheritance: In DDG2P, the MOI is recorded as hemizygous for CK SYNDROME and x-linked dominant for CONGENITAL HEMIDYSPLASIA WITH ICHTHYOSIFORM ERYTHRODERMA AND LIMB DEFECTS.
DDG2P v1.47 NSDHL Rebecca Foulger Mode of inheritance for gene: NSDHL 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)
DDG2P v1.46 PDHA1 Rebecca Foulger Added comment: Comment on mode of inheritance: IN DDG2P, the MOI is listed as hemizygous for INTELLECTUAL DISABILTIY (note typo in DDG2P disease name); x-linked dominant for PYRUVATE DEHYDROGENASE E1-ALPHA DEFICIENCY IN FEMALES; hemizygous for X-LINKED LEIGH SYNDROME. All disorders have a confirmed Disease confidence rating. Therefore have selected an X-linked dominant MOI in PanelApp so all cases can be caught.
DDG2P v1.46 PDHA1 Rebecca Foulger Mode of inheritance for gene: PDHA1 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)
Osteogenesis imperfecta v1.43 GORAB Eleanor Williams Classified gene: GORAB as Green List (high evidence)
Osteogenesis imperfecta v1.43 GORAB Eleanor Williams Added comment: Comment on list classification: Following discussion in the GMS musculoskeletal specialist test group Webex on 2019-06-04 it was decided to rate this gene green. Sufficient cases.
Osteogenesis imperfecta v1.43 GORAB Eleanor Williams Gene: gorab has been classified as Green List (High Evidence).
Osteogenesis imperfecta v1.42 GORAB Eleanor Williams Mode of inheritance for gene: GORAB was changed from to BIALLELIC, autosomal or pseudoautosomal
Osteogenesis imperfecta v1.41 DSPP Eleanor Williams Classified gene: DSPP as Green List (high evidence)
Osteogenesis imperfecta v1.41 DSPP Eleanor Williams Added comment: Comment on list classification: Following discussion in the GMS musculoskeletal specialist test group Webex on 2019-06-04 it was decided to make this gene green. Sufficient cases.
Osteogenesis imperfecta v1.41 DSPP Eleanor Williams Gene: dspp has been classified as Green List (High Evidence).
Osteogenesis imperfecta v1.40 DSPP Eleanor Williams Mode of inheritance for gene: DSPP was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Osteogenesis imperfecta v1.39 CREB3L1 Eleanor Williams Classified gene: CREB3L1 as Green List (high evidence)
Osteogenesis imperfecta v1.39 CREB3L1 Eleanor Williams Added comment: Comment on list classification: Following discussion in the GMS musculoskeletal specialist test group Webex on 2019-06-04 it was decided to make this green gene. There is more evidence since the last review.
Osteogenesis imperfecta v1.39 CREB3L1 Eleanor Williams Gene: creb3l1 has been classified as Green List (High Evidence).
Rare multisystem ciliopathy disorders v1.86 ARMC9 Rebecca Foulger Classified gene: ARMC9 as Green List (high evidence)
Rare multisystem ciliopathy disorders v1.86 ARMC9 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Green to Red. Confirmed Disease confidence rating in DDG2P for Joubert syndrome 30. Green rating by Zornitza Stark and Olivia Niblock. Sufficient cases to support causation from PMID:28625504: In 11 patients from 8 unrelated families with Joubert syndrome-30 (MIM:617622), Van De Weghe et al. (2017, PMID:28625504) identified 10 different homozygous or compound heterozygous variants in the ARMC9 gene. Variants in the first 2 families were found by WES of 53 patients from 51 families with a clinical diagnosis of Joubert syndrome. Variants in 3 additional unrelated patients were found by targeted sequencing of the ARMC9 gene, and the remaining 2 families were ascertained from a cohort of Saudi Arabian families who underwent exome sequencing.
Rare multisystem ciliopathy disorders v1.86 ARMC9 Rebecca Foulger Gene: armc9 has been classified as Green List (High Evidence).
Rare multisystem ciliopathy disorders v1.85 ARMC9 Rebecca Foulger Phenotypes for gene: ARMC9 were changed from Joubert syndrome to Joubert syndrome 30, 617622
Osteogenesis imperfecta v1.38 B4GALT7 Eleanor Williams Mode of inheritance for gene: B4GALT7 was changed from to BIALLELIC, autosomal or pseudoautosomal
Osteogenesis imperfecta v1.37 CASR Eleanor Williams Mode of inheritance for gene: CASR was changed from to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Osteogenesis imperfecta v1.36 COL11A2 Eleanor Williams commented on gene: COL11A2: Following discussion in the GMS musculoskeletal specialist test group Webex on 2019-06-04 it was decided to keep this gene red as it is associated with Stickler syndrome which is covered by other panels.
Osteogenesis imperfecta v1.36 COL11A1 Eleanor Williams commented on gene: COL11A1: Following discussion in the GMS musculoskeletal specialist test group Webex on 2019-06-04 it was decided to keep this gene red as it is associated with Stickler syndrome which is covered by other panels.
Osteogenesis imperfecta v1.36 CASR Eleanor Williams commented on gene: CASR: This gene was discussed in the GMS musculoskeletal specialist test group Webex on 2019-06-04. It was decided that due to further evidence, it should be made green.
Osteogenesis imperfecta v1.36 CASR Eleanor Williams commented on gene: CASR: Associated with Hyperparathyroidism, neonatal, Hypocalcemia, autosomal dominant, Hypocalcemia, autosomal dominant, with Bartter syndrome and Hypocalciuric hypercalcemia, type I in OMIM.

Multiple fractures is listed as one of the clinical phenotypes for Hyperparathyroidism, neonatal in OMIM.

PMID: 22620673 - Tonyushkina et al 2012 - report a case of an unusually severe neonatal Familial Hypocalciuric Hypercalcemia due to a novel CaSR gene mutation that presented with perinatal fractures and moderate hypercalcemia. A heterozygous nucleotide substitution c.1664 T>C in exon 6, resulting in an amino acid change I555T.

PMID: 30376845 - Capozza et al 2018 - report a case of a child with Neonatal severe primary hyperparathyroidism. Phenotype included fracture of the humerus neck and severe osteoporosis. The patient was found to have a homozygous novel mutation of the splicing donor site of the intron 5 ( c.1608 + 1G > A –IVS5 + 1G > A. Both asymptomatic parents were found to be heterozygous.

PMID: 26161261 - Fisher et al 2015 - report two unrelated patients with neonatal severe hyperparathyroidism and de novo R185Q heterozygous inactivating CASR mutations. Patient 2 had multiple rib fractures.

Summary: 3 cases reported of patients with variants in CASR and neonatal severe hyperparathyroidism or severe neonatal Familial Hypocalciuric Hypercalcemia. Patients homo- and hetero-zygous for variants in CASR are reported.
Hereditary neuropathy v1.300 ZFYVE26 Louise Daugherty commented on gene: ZFYVE26: Review and rating uploaded from file (Curation_Template_GMS_Neuro_AR_20190521.xlsx) submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group.
Hereditary neuropathy v1.300 XRCC1 Louise Daugherty commented on gene: XRCC1: Review and rating uploaded from file (Curation_Template_GMS_Neuro_AR_20190521.xlsx) submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group.
Hereditary neuropathy v1.300 XPA Louise Daugherty commented on gene: XPA: Review and rating uploaded from file (Curation_Template_GMS_Neuro_AR_20190521.xlsx) submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group.
Hereditary neuropathy v1.300 XK Louise Daugherty commented on gene: XK: Review and rating uploaded from file (Curation_Template_GMS_Neuro_AR_20190521.xlsx) submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group.
Hereditary neuropathy v1.300 WARS Louise Daugherty commented on gene: WARS: Review and rating uploaded from file (Curation_Template_GMS_Neuro_AR_20190521.xlsx) submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group.
Hereditary neuropathy v1.300 VRK1 Louise Daugherty edited their review of gene: VRK1: Added comment: Review and rating uploaded from file (Curation_Template_GMS_Neuro_AR_20190521.xlsx) submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group.; Changed rating: AMBER
Hereditary neuropathy v1.300 VPS13A Louise Daugherty commented on gene: VPS13A: Review and rating uploaded from file (Curation_Template_GMS_Neuro_AR_20190521.xlsx) submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group.
Hereditary neuropathy v1.300 VCP Louise Daugherty commented on gene: VCP: Review and rating uploaded from file (Curation_Template_GMS_Neuro_AR_20190521.xlsx) submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group.
Hereditary neuropathy v1.300 TWNK Louise Daugherty commented on gene: TWNK: Review and rating uploaded from file (Curation_Template_GMS_Neuro_AR_20190521.xlsx) submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group.
Hereditary neuropathy v1.300 TTPA Louise Daugherty commented on gene: TTPA: Review and rating uploaded from file (Curation_Template_GMS_Neuro_AR_20190521.xlsx) submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group.
Hereditary neuropathy v1.300 SURF1 Louise Daugherty commented on gene: SURF1: Review and rating uploaded from file (Curation_Template_GMS_Neuro_AR_20190521.xlsx) submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group.
Hereditary neuropathy v1.300 SUCLA2 Louise Daugherty commented on gene: SUCLA2: Review and rating uploaded from file (Curation_Template_GMS_Neuro_AR_20190521.xlsx) submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group.
Hereditary neuropathy v1.300 SPG7 Louise Daugherty commented on gene: SPG7: Review and rating uploaded from file (Curation_Template_GMS_Neuro_AR_20190521.xlsx) submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group.
Hereditary neuropathy v1.300 SPG11 Louise Daugherty commented on gene: SPG11: Review and rating uploaded from file (Curation_Template_GMS_Neuro_AR_20190521.xlsx) submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group.
Hereditary neuropathy v1.300 SPAST Louise Daugherty commented on gene: SPAST: Review and rating uploaded from file (Curation_Template_GMS_Neuro_AR_20190521.xlsx) submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group.
Hereditary neuropathy v1.300 SOX10 Louise Daugherty commented on gene: SOX10: Review and rating uploaded from file (Curation_Template_GMS_Neuro_AR_20190521.xlsx) submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group.
Hereditary neuropathy v1.300 SLC5A7 Louise Daugherty commented on gene: SLC5A7: Review and rating uploaded from file (Curation_Template_GMS_Neuro_AR_20190521.xlsx) submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group.
Hereditary neuropathy v1.300 SLC25A46 Louise Daugherty commented on gene: SLC25A46: Review and rating uploaded from file (Curation_Template_GMS_Neuro_AR_20190521.xlsx) submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group.
Hereditary neuropathy v1.300 SLC25A19 Louise Daugherty commented on gene: SLC25A19: Review and rating uploaded from file (Curation_Template_GMS_Neuro_AR_20190521.xlsx) submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group.
Hereditary neuropathy v1.300 SELENOI Louise Daugherty commented on gene: SELENOI: Review and rating uploaded from file (Curation_Template_GMS_Neuro_AR_20190521.xlsx) submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group.
Hereditary neuropathy v1.300 SCYL1 Louise Daugherty commented on gene: SCYL1: Review and rating uploaded from file (Curation_Template_GMS_Neuro_AR_20190521.xlsx) submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group.
Hereditary neuropathy v1.300 SCP2 Louise Daugherty commented on gene: SCP2: Review and rating uploaded from file (Curation_Template_GMS_Neuro_AR_20190521.xlsx) submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group.
Hereditary neuropathy v1.300 SCARB2 Louise Daugherty commented on gene: SCARB2: Review and rating uploaded from file (Curation_Template_GMS_Neuro_AR_20190521.xlsx) submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group.
Hereditary neuropathy v1.300 PTRH2 Louise Daugherty commented on gene: PTRH2: Review and rating uploaded from file (Curation_Template_GMS_Neuro_AR_20190521.xlsx) submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group.
Hereditary neuropathy v1.300 PTPN11 Louise Daugherty commented on gene: PTPN11: Review and rating uploaded from file (Curation_Template_GMS_Neuro_AR_20190521.xlsx) submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group.
Hereditary neuropathy v1.300 PTEN Louise Daugherty commented on gene: PTEN: Review and rating uploaded from file (Curation_Template_GMS_Neuro_AR_20190521.xlsx) submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group.
Hereditary neuropathy v1.300 PRKCG Louise Daugherty commented on gene: PRKCG: Review and rating uploaded from file (Curation_Template_GMS_Neuro_AR_20190521.xlsx) submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group.
Hereditary neuropathy v1.300 PPOX Louise Daugherty commented on gene: PPOX: Review and rating uploaded from file (Curation_Template_GMS_Neuro_AR_20190521.xlsx) submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group.
Hereditary neuropathy v1.300 POLR3A Louise Daugherty commented on gene: POLR3A: Review and rating uploaded from file (Curation_Template_GMS_Neuro_AR_20190521.xlsx) submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group.
Hereditary neuropathy v1.300 PNPLA6 Louise Daugherty commented on gene: PNPLA6: Review and rating uploaded from file (Curation_Template_GMS_Neuro_AR_20190521.xlsx) submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group.
Hereditary neuropathy v1.300 PNKP Louise Daugherty commented on gene: PNKP: Review and rating uploaded from file (Curation_Template_GMS_Neuro_AR_20190521.xlsx) submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group.
Hereditary neuropathy v1.300 PMP2 Louise Daugherty commented on gene: PMP2: Review and rating uploaded from file (Curation_Template_GMS_Neuro_AR_20190521.xlsx) submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group.
Hereditary neuropathy v1.300 PMM2 Louise Daugherty commented on gene: PMM2: Review and rating uploaded from file (Curation_Template_GMS_Neuro_AR_20190521.xlsx) submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group.
Hereditary neuropathy v1.300 XRCC1 Louise Daugherty reviewed gene: XRCC1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 XPA Louise Daugherty reviewed gene: XPA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 XK Louise Daugherty reviewed gene: XK: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 VPS13A Louise Daugherty reviewed gene: VPS13A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 SUCLA2 Louise Daugherty reviewed gene: SUCLA2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 SLC25A46 Louise Daugherty reviewed gene: SLC25A46: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 SLC25A19 Louise Daugherty reviewed gene: SLC25A19: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 SELENOI Louise Daugherty reviewed gene: SELENOI: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 SCYL1 Louise Daugherty reviewed gene: SCYL1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 SCP2 Louise Daugherty reviewed gene: SCP2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 SCARB2 Louise Daugherty reviewed gene: SCARB2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 PTRH2 Louise Daugherty reviewed gene: PTRH2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 PTEN Louise Daugherty reviewed gene: PTEN: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 PRKCG Louise Daugherty commented on gene: PRKCG: Review and rating uploaded from file (Curation_Template_GMS_Neuro_AR_20190521.xlsx) submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group.
Hereditary neuropathy v1.300 PPOX Louise Daugherty reviewed gene: PPOX: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 POLR3A Louise Daugherty reviewed gene: POLR3A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 PNKP Louise Daugherty reviewed gene: PNKP: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 PMM2 Louise Daugherty reviewed gene: PMM2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 PEX10 Louise Daugherty reviewed gene: PEX10: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 PDYN Louise Daugherty reviewed gene: PDYN: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 OPA3 Louise Daugherty reviewed gene: OPA3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 OPA1 Louise Daugherty reviewed gene: OPA1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 NAGA Louise Daugherty reviewed gene: NAGA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 MT-TL1 Louise Daugherty reviewed gene: MT-TL1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 MT-RNR1 Louise Daugherty reviewed gene: MT-RNR1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 MMACHC Louise Daugherty reviewed gene: MMACHC: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 LYST Louise Daugherty reviewed gene: LYST: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 KLC2 Louise Daugherty reviewed gene: KLC2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 KCNA2 Louise Daugherty reviewed gene: KCNA2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 IARS2 Louise Daugherty reviewed gene: IARS2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 HMBS Louise Daugherty reviewed gene: HMBS: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 GLE1 Louise Daugherty reviewed gene: GLE1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 GJC2 Louise Daugherty reviewed gene: GJC2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 GBA2 Louise Daugherty reviewed gene: GBA2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 GALC Louise Daugherty reviewed gene: GALC: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 FLVCR1 Louise Daugherty reviewed gene: FLVCR1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 FAM126A Louise Daugherty reviewed gene: FAM126A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 FAH Louise Daugherty reviewed gene: FAH: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 FA2H Louise Daugherty reviewed gene: FA2H: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 ETFDH Louise Daugherty reviewed gene: ETFDH: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 ERCC8 Louise Daugherty reviewed gene: ERCC8: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 ERCC6 Louise Daugherty reviewed gene: ERCC6: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 ERBB3 Louise Daugherty reviewed gene: ERBB3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 DSTYK Louise Daugherty reviewed gene: DSTYK: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 DNAJC3 Louise Daugherty reviewed gene: DNAJC3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 DGUOK Louise Daugherty reviewed gene: DGUOK: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 DEGS1 Louise Daugherty reviewed gene: DEGS1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 DARS2 Louise Daugherty reviewed gene: DARS2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 CYP27A1 Louise Daugherty reviewed gene: CYP27A1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 CPOX Louise Daugherty reviewed gene: CPOX: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 COA7 Louise Daugherty reviewed gene: COA7: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 CD59 Louise Daugherty reviewed gene: CD59: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 C19orf12 Louise Daugherty reviewed gene: C19orf12: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 BCKDHB Louise Daugherty reviewed gene: BCKDHB: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 B4GALNT1 Louise Daugherty reviewed gene: B4GALNT1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 ARSA Louise Daugherty reviewed gene: ARSA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 ARL6IP1 Louise Daugherty reviewed gene: ARL6IP1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 APOA1 Louise Daugherty reviewed gene: APOA1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 AP1S1 Louise Daugherty reviewed gene: AP1S1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 AGXT Louise Daugherty reviewed gene: AGXT: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 AGTPBP1 Louise Daugherty reviewed gene: AGTPBP1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 ABHD12 Louise Daugherty reviewed gene: ABHD12: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy v1.300 ABCA1 Louise Daugherty reviewed gene: ABCA1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.284 POMK Rebecca Foulger Marked gene: POMK as ready
Fetal anomalies v0.284 POMK Rebecca Foulger Gene: pomk has been classified as Green List (High Evidence).
Fetal anomalies v0.284 COG4 Rebecca Foulger Marked gene: COG4 as ready
Fetal anomalies v0.284 COG4 Rebecca Foulger Gene: cog4 has been classified as Green List (High Evidence).
Fetal anomalies v0.284 HNRNPK Rebecca Foulger Marked gene: HNRNPK as ready
Fetal anomalies v0.284 HNRNPK Rebecca Foulger Added comment: Comment when marking as ready: Anna de Burca (Genomics England clinical team) confirmed that Green rating was correct for HNRNPK.
Fetal anomalies v0.284 HNRNPK Rebecca Foulger Gene: hnrnpk has been classified as Green List (High Evidence).
Osteogenesis imperfecta v1.36 B4GALT7 Eleanor Williams commented on gene: B4GALT7: This gene was discussed in the GMS musculoskeletal specialist test group Webex on 2019-06-04. It was decided that due to further evidence, it should be made green.
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.122 JAG1 Eleanor Williams Mode of inheritance for gene: JAG1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.284 MYRF Rebecca Foulger Classified gene: MYRF as Green List (high evidence)
Fetal anomalies v0.284 MYRF Rebecca Foulger Added comment: Comment on list classification: Updated rating from Grey to Green. MYRF gene was added to the panel and reviewed by Julia Baptista. Sufficient cases to support MYRF variants causing Cardiac-urogenital syndrome (MIM:618280) from Pinz et al 2018 (PMID:29446546), Chitayat et al., (PMID:30070761), Qi et al.,2018 (PMID:30532227) and Rossetti et al., 2019 (PMID: 31069960). The phenotype is fetally-relevant (includes congenital diaphragmatic hernia/CDH, genital defects and cardiac defects) with multiple papers reporting detection in-utero: In both patients identified in Pinz et al 2018, anomalies were detected by ultrasound at 20 weeks gestation: mesocardia without other signs of heterotaxy (Patient 1), and a complex congenital heart defect with pericardial effusion (Patient 2). Chitayat et al., report a fetus with a novel de novo LOF variant in MYRF and a hypoplastic left heart and female external genitalia. In Rossetti et al., 2019, cardiac malformation and/or CDH was detected on a prenatal ultrasound.
Fetal anomalies v0.284 MYRF Rebecca Foulger Gene: myrf has been classified as Green List (High Evidence).
Fetal anomalies v0.283 MYRF Rebecca Foulger Added comment: Comment on publications: PMID:30985895 (Hamanaka et al., 2019) also report (in an enrichment study plus an independent cohort) that MYRF haploinsufficiencey causes disorders of sex development.
Fetal anomalies v0.283 MYRF Rebecca Foulger Publications for gene: MYRF were set to 30532227; 30985895; 31069960; 30070761; 29446546
Osteogenesis imperfecta v1.36 B4GALT7 Eleanor Williams Publications for gene: B4GALT7 were set to 15211654; 26940150
Fetal anomalies v0.282 MYRF Rebecca Foulger Mode of inheritance for gene: MYRF was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v0.281 MYRF Rebecca Foulger Phenotypes for gene: MYRF were changed from congenital diaphragmatic hernia, cardiac defect, disorders of sexual development to Cardiac-urogenital syndrome, 618280; Congenital diaphragmatic hernia (CDH); Disorders of sex development (DSD)
Fetal anomalies v0.280 MYRF Rebecca Foulger Publications for gene: MYRF were set to PMID: 30532227; 30985895; 31069960; 30070761; 29446546 )
Osteogenesis imperfecta v1.35 B4GALT7 Eleanor Williams commented on gene: B4GALT7: Associated with Ehlers-Danlos syndrome, spondylodysplastic type, 1 (#130070) in OMIM.

PMID: 26940150 - Salter et al 2016 - two unrelated patients with compound heterozygous mutations in B4GALT7. Both showed osteopenia (one with fractures, other patient had mild osteopenia). They review the phenotypes reported in previous cases (Table 1): 1 case with osteopenia reported in Faiyaz‐Ul‐Haque et al. [2004] , 1 case reported in Kresse et al. [1987] (with possible rib fracture).

Summary: 3 cases of patients with homozygous or compound heterozygous variants in B4GALT7 and osteopenia, two with fractures.
Fetal anomalies v0.279 H19 Rebecca Foulger Classified gene: H19 as Red List (low evidence)
Fetal anomalies v0.279 H19 Rebecca Foulger Added comment: Comment on list classification: Demoted gene from Green to Red based on group clinical review, and confirmation from Richard Scott.
Fetal anomalies v0.279 H19 Rebecca Foulger Gene: h19 has been classified as Red List (Low Evidence).
Fetal anomalies v0.278 H19 Rebecca Foulger commented on gene: H19: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in Spring 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Epigenetic. Action taken: Demoted H19 gene rating from Green to Red. Additional notes from clinical review: Relevant variants are in the upstream methylation region rather than the coding region, and therefore won't be detected on the exome.
Fetal anomalies v0.278 H19 Richard Scott reviewed gene: H19: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ehlers Danlos syndrome with a likely monogenic cause v1.58 SMAD4 Eleanor Williams Classified gene: SMAD4 as No list
Ehlers Danlos syndrome with a likely monogenic cause v1.58 SMAD4 Eleanor Williams Added comment: Comment on list classification: Following discussion in the GMS musculoskeletal specialist test group Webex on 2019-06-04, it was decided to remove this gene from the panel as there is not enough overlap with the EDS phenotype.
Ehlers Danlos syndrome with a likely monogenic cause v1.58 SMAD4 Eleanor Williams Gene: smad4 has been removed from the panel.
Ehlers Danlos syndrome with a likely monogenic cause v1.57 COL9A3 Eleanor Williams Classified gene: COL9A3 as No list
Ehlers Danlos syndrome with a likely monogenic cause v1.57 COL9A3 Eleanor Williams Added comment: Comment on list classification: Following discussion in the GMS musculoskeletal specialist test group Webex on 2019-06-04, it was decided to remove the genes associated with Stickler syndrome from this panel. These genes are better covered by other panels.
Ehlers Danlos syndrome with a likely monogenic cause v1.57 COL9A3 Eleanor Williams Gene: col9a3 has been removed from the panel.
Ehlers Danlos syndrome with a likely monogenic cause v1.56 COL9A2 Eleanor Williams Classified gene: COL9A2 as No list
Ehlers Danlos syndrome with a likely monogenic cause v1.56 COL9A2 Eleanor Williams Added comment: Comment on list classification: Following discussion in the GMS musculoskeletal specialist test group Webex on 2019-06-04, it was decided to remove the genes associated with Stickler syndrome from this panel. These genes are better covered by other panels.
Ehlers Danlos syndrome with a likely monogenic cause v1.56 COL9A2 Eleanor Williams Gene: col9a2 has been removed from the panel.
Ehlers Danlos syndrome with a likely monogenic cause v1.55 COL9A1 Eleanor Williams Classified gene: COL9A1 as No list
Ehlers Danlos syndrome with a likely monogenic cause v1.55 COL9A1 Eleanor Williams Added comment: Comment on list classification: Following discussion in the GMS musculoskeletal specialist test group Webex on 2019-06-04, it was decided to remove the genes associated with Stickler syndrome from this panel. These genes are better covered by other panels.
Ehlers Danlos syndrome with a likely monogenic cause v1.55 COL9A1 Eleanor Williams Gene: col9a1 has been removed from the panel.
Ehlers Danlos syndrome with a likely monogenic cause v1.54 COL11A2 Eleanor Williams Classified gene: COL11A2 as No list
Ehlers Danlos syndrome with a likely monogenic cause v1.54 COL11A2 Eleanor Williams Added comment: Comment on list classification: Following discussion in the GMS musculoskeletal specialist test group Webex on 2019-06-04, it was decided to remove the genes associated with Stickler syndrome from this panel. These genes are better covered by other panels.
Ehlers Danlos syndrome with a likely monogenic cause v1.54 COL11A2 Eleanor Williams Gene: col11a2 has been removed from the panel.
Ehlers Danlos syndrome with a likely monogenic cause v1.53 COL11A1 Eleanor Williams Classified gene: COL11A1 as No list
Ehlers Danlos syndrome with a likely monogenic cause v1.53 COL11A1 Eleanor Williams Added comment: Comment on list classification: Following discussion in the GMS musculoskeletal specialist test group Webex on 2019-06-04, it was decided to remove the genes associated with Stickler syndrome from this panel. These genes are better covered by other panels.
Ehlers Danlos syndrome with a likely monogenic cause v1.53 COL11A1 Eleanor Williams Gene: col11a1 has been removed from the panel.
Ehlers Danlos syndrome with a likely monogenic cause v1.52 GGCX Eleanor Williams Classified gene: GGCX as No list
Ehlers Danlos syndrome with a likely monogenic cause v1.52 GGCX Eleanor Williams Added comment: Comment on list classification: Following discussion at the GMS musculoskeletal specialist test group Webex on 2019-06-04, removing this gene from the panel as the associated PXE phenotype is beyond the scope of this panel.
Ehlers Danlos syndrome with a likely monogenic cause v1.52 GGCX Eleanor Williams Gene: ggcx has been removed from the panel.
Ehlers Danlos syndrome with a likely monogenic cause v1.51 ABCC6 Eleanor Williams Classified gene: ABCC6 as No list
Ehlers Danlos syndrome with a likely monogenic cause v1.51 ABCC6 Eleanor Williams Added comment: Comment on list classification: Following discussion at the GMS musculoskeletal specialist test group Webex on 2019-06-04, removing this gene from the panel as the associated PXE phenotype is beyond the scope of this panel.
Ehlers Danlos syndrome with a likely monogenic cause v1.51 ABCC6 Eleanor Williams Gene: abcc6 has been removed from the panel.
Amelogenesis imperfecta v1.14 DLX3 Eleanor Williams Added comment: Comment on phenotypes: Adding phenotype of Tricho-Dento-Osseous syndrome , Amelogenesis Imperfecta, hypoplastic to this gene at suggestion of Dr Susan Parekh (Consultant in Pediatric Dentistry, GOSH)
Amelogenesis imperfecta v1.14 DLX3 Eleanor Williams Phenotypes for gene: DLX3 were changed from Amelogenesis imperfecta, type IV, 104510; Amelogenesis Imperfecta, Type IV, 104510; Amelogenesis Imperfecta, Dominant; amelogenesis imperfecta with taurodontism; Trichodontoosseous syndrome, 190320; Tricho-dento-osseous syndrome (TDO) (includes enamel hypoplasia); hypoplastic AI, taurodontism and kinky hair to Amelogenesis imperfecta, type IV, 104510; Amelogenesis Imperfecta, Type IV, 104510; Amelogenesis Imperfecta, Dominant; amelogenesis imperfecta with taurodontism; Trichodontoosseous syndrome, 190320; Tricho-dento-osseous syndrome (TDO) (includes enamel hypoplasia); hypoplastic AI, taurodontism and kinky hair; Tricho-Dento-Osseous syndrome , Amelogenesis Imperfecta, hypoplastic
Intellectual disability v2.862 USP7 Rebecca Foulger Publications for gene: USP7 were set to
Intellectual disability v2.861 POLA1 Rebecca Foulger Classified gene: POLA1 as Green List (high evidence)
Intellectual disability v2.861 POLA1 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Red to Green based on additional 2019 paper provided by Konstantinos Varvagiannis. PMID:31006512 (Van Esch et al., 2019) report 9 additional males from 5 families hemizygous for POLA1. ID or DD was a feature in all patients (Table 1) and is seen alongside short stature, microcephaly and hypogonadism. The phenotype was distinct from the previously-reported XLPDR. Although the phenotype spectrum is broad for POLA1 variants, there are sufficient cases of ID/DD (>3 from PMID:31006512 and PMID:27019227, with ID/DD being a consistent phenotype in PMID:31006512 individuals), thereby warranting a Green rating.
Intellectual disability v2.861 POLA1 Rebecca Foulger Gene: pola1 has been classified as Green List (High Evidence).
Intellectual disability v2.860 POLA1 Rebecca Foulger Publications for gene: POLA1 were set to 15844784; 27019227; 19377476
Intellectual disability v2.859 POLA1 Rebecca Foulger Phenotypes for gene: POLA1 were changed from Pigmentary disorder, reticulate, with systemic manifestations, X-linked, 301220; XLPDR to Pigmentary disorder, reticulate, with systemic manifestations, X-linked, 301220; XLPDR; X-Linked Intellectual Disability associated with short stature, microcephaly, and hypogonadism
Intellectual disability v2.858 ASH1L Ellen McDonagh Publications for gene: ASH1L were set to 25961944; 26350204; 29276005; 29753921
Early onset or syndromic epilepsy v1.54 Ellen McDonagh Panel status changed from internal to public
Cytopenias and congenital anaemias v1.69 SLC46A1 Julia Baptista gene: SLC46A1 was added
gene: SLC46A1 was added to Cytopenias and congenital anaemias. Sources: Expert Review,Literature
Mode of inheritance for gene: SLC46A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC46A1 were set to PMID: 21333572; 17446347; 29390264; 11804211; 17641272
Phenotypes for gene: SLC46A1 were set to Folate malabsorption; anemia; pancytopenia
Review for gene: SLC46A1 was set to GREEN
Added comment: Hereditary folate malabsorption is an autosomal recessive disorder, shown to be due to loss-of-function mutations of the proton-coupled folate transporter (SLC46A1). Affected individuals present with early onset macrocytic anemia, thrombocytopenia, neutropenia, leukopenianand/or pancytopenia.
Sources: Expert Review, Literature
Intellectual disability v2.857 MED12L Konstantinos Varvagiannis gene: MED12L was added
gene: MED12L was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: MED12L was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MED12L were set to 31155615
Phenotypes for gene: MED12L were set to Motor delay; Delayed speech and language development; Intellectual disability; Behavioral abnormality; Abnormality of the abdomen; Seizures; Abnormality of the corpus callosum
Penetrance for gene: MED12L were set to unknown
Review for gene: MED12L was set to AMBER
Added comment: Nizon et al. (2019 - PMID: 31155615) report on 7 unrelated individuals with nucleotide or copy-number variants in MED12L.

Features included motor delay (4/7), speech impairment (7/7) with ID of variable degrees (7/7 - mild to severe). Variable behavioral abnormalities (ASD in 4/7, aggressive behavior, ADHD, etc), functional GI anomalies, corpus callosum abnormalities and seizures were among other features noted in some/few. There was no recognizable facial phenotype.

Nucleotide variants included 1 stopgain, 1 frameshift and 2 splice site variants. 3 CNVs were reported (two 3q25.1 microduplications of 460- and 147-kb respectively and one microdeletion of 291-kb) although all spanned also other genes.

De novo occurrence was shown for 2 CNVs and 2 SNVs, as parental samples were unavailable for 3 of the subjects.

Contribution of other genetic (eg. an inherited 22q11.2 microduplication, VUS in other genes) or environmental factors could not be ruled out for few individuals.

Among the arguments provided:

MED12L encodes a subunit of the kinase module of the mediator complex, a complex required for transcription by RNA polymerase II. Mutations in other subunits of the kinase module (eg. MED12, MED13L, etc) have been implicated in intellectual disability.

The protein is localized in the nucleus. The gene is mainly expressed in the brain.

The functional effect of 2 CNVs was evaluated using the recovery of RNA synthesis assay, an assay reflecting global transcriptional activity. Fibrobast studies from one individual with microdeletion and one further subject with microduplication demonstrated decreased RNA synthesis compared to controls. Decreased RNA synthesis was also observed in cell lines from individuals with mutations in other genes for subunits of the mediator complex (eg. MED12 or MED13L) or from individuals with Cockayne syndrome.

Therefore haploinsufficiency is suggested to underly the transcriptional defect. (MED12L also appears to be intolerant to LoF variation with a pLI score of 1).

Some features appear to be common among the disorders caused by pathogenic variants in MED12L or other subunits of the kinase module (MED12, MED13, MED13L) eg. ID, abnormal behaviour or autistic features.

Animal models are not discussed / (probably not) available (MGI for Med12l : http://www.informatics.jax.org/marker/MGI:2139916).

MED12L is not associated with any phenotype in OMIM or G2P. The gene is not commonly included in gene panels for ID offered by diagnostic laboratories.

As a result, this gene can be considered for inclusion in the ID panel, probably as amber (4 variants affecting only MED12L, segregation studies performed for 2, degree of ID reported mild on 2 occasions) pending further reports.
Sources: Literature
Hereditary neuropathy v1.299 ABCA1 Louise Daugherty Phenotypes for gene: ABCA1 were changed from to Tangier disease, 205400; Multifocal relapsing mononeuropathies. Orange tonsils, organomegaly; pain, paresthesias, anaesthesia
Hereditary neuropathy v1.298 ABCA1 Louise Daugherty Publications for gene: ABCA1 were set to
Hereditary neuropathy v1.297 ABCA1 Louise Daugherty Mode of inheritance for gene: ABCA1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.296 ABHD12 Louise Daugherty Mode of inheritance for gene: ABHD12 was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.295 ABHD12 Louise Daugherty Publications for gene: ABHD12 were set to
Hereditary neuropathy v1.294 ABHD12 Louise Daugherty Phenotypes for gene: ABHD12 were changed from to Neurodegeneration, childhood-onset, with cerebellar atrophy,612674; Onset 2nd decade, neuropathy with SNCV, sensory neuronal hearing loss, retinitis pigmentosa, spastic paraplegia, ataxia
Hereditary neuropathy v1.293 AGTPBP1 Louise Daugherty Phenotypes for gene: AGTPBP1 were changed from to Neurodegeneration, childhood-onset, with cerebellar atrophy, 618276; Early onset cerebellar atrophy, developmental delay, and feeding and respiratory difficulties, severe motor neuronopathy
Hereditary neuropathy v1.292 AGTPBP1 Louise Daugherty Publications for gene: AGTPBP1 were set to
Hereditary neuropathy v1.291 AGTPBP1 Louise Daugherty Mode of inheritance for gene: AGTPBP1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.290 AGXT Louise Daugherty Publications for gene: AGXT were set to
Hereditary neuropathy v1.289 AGXT Louise Daugherty Phenotypes for gene: AGXT were changed from to Hyperoxaluria, primary, type 1, 259900; Renal failure and deposition of calcium oxalate crystals in tissues including nerve and muscle. Sensory and motor axonal neuropathy (some slowing)
Hereditary neuropathy v1.288 AGXT Louise Daugherty Mode of inheritance for gene: AGXT was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.287 AP1S1 Louise Daugherty Publications for gene: AP1S1 were set to
Hereditary neuropathy v1.286 AP1S1 Louise Daugherty Phenotypes for gene: AP1S1 were changed from to MEDNIK syndrome, 609313; Congenital onset, Mental retardation, Enteropathy (severe congenital diarrhoea), Deafness, sensory-motor Neuropathy with intermediate conduction velocities, Ichthyosis, Keratoderma
Hereditary neuropathy v1.285 AP1S1 Louise Daugherty Mode of inheritance for gene: AP1S1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.284 APOA1 Louise Daugherty Phenotypes for gene: APOA1 were changed from to Renal failure, Axonal sensory-motor neuropathy similar to TTR FAP, amyloid nephropathy
Hereditary neuropathy v1.283 APOA1 Louise Daugherty Publications for gene: APOA1 were set to
Hereditary neuropathy v1.282 APOA1 Louise Daugherty Mode of inheritance for gene: APOA1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy v1.281 ARL6IP1 Louise Daugherty Publications for gene: ARL6IP1 were set to
Hereditary neuropathy v1.280 ARL6IP1 Louise Daugherty Phenotypes for gene: ARL6IP1 were changed from to Spastic paraplegia 61, autosomal recessive, 615685; Childhood onset spastic paraplegia with mutilating, sensory to motor axonal neuropathy
Hereditary neuropathy v1.279 ARL6IP1 Louise Daugherty Mode of inheritance for gene: ARL6IP1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.278 ARSA Louise Daugherty Phenotypes for gene: ARSA were changed from to Metachromatic leukodystrophy, 250100; Severe late infantile form with mental retardation and severe course. Regression before 30 months; adult onset, psychiatric symptoms, leukodystrophy on MRI, progressive neuropathy with SNCV, optic atrophy
Hereditary neuropathy v1.277 ARSA Louise Daugherty Mode of inheritance for gene: ARSA was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.276 B4GALNT1 Louise Daugherty Publications for gene: B4GALNT1 were set to
Hereditary neuropathy v1.275 B4GALNT1 Louise Daugherty Mode of inheritance for gene: B4GALNT1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.274 B4GALNT1 Louise Daugherty Phenotypes for gene: B4GALNT1 were changed from to Spastic paraplegia 26, autosomal recessive, 609195; SPG26; Spastic paraplegia, intellectual disability, ataxia, dystonia, axonal sensory-motor neuropathy
Hereditary neuropathy v1.273 BCKDHB Louise Daugherty Phenotypes for gene: BCKDHB were changed from to Maple syrup urine disease, type Ib, 248600; Maple Syrup Urine Disease; Metabolic encephalopathy, elevated branched chain amino acids in urine, acute axonal neuropath
Hereditary neuropathy v1.272 BCKDHB Louise Daugherty Publications for gene: BCKDHB were set to
Hereditary neuropathy v1.271 BCKDHB Louise Daugherty Mode of inheritance for gene: BCKDHB was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.270 C19orf12 Louise Daugherty Publications for gene: C19orf12 were set to
Hereditary neuropathy v1.269 C19orf12 Louise Daugherty Phenotypes for gene: C19orf12 were changed from to Spastic paraplegia 43, autosomal recessive, 615043; Neurodegeneration with brain iron accumulation 4, 614298; SPG43, Childhood onset spastic paraplegia and sensory-motor axonal neuropathy, NBIA with optic atrophy, extrapyramidal signs
Hereditary neuropathy v1.268 C19orf12 Louise Daugherty Mode of inheritance for gene: C19orf12 was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.268 C19orf12 Louise Daugherty Mode of inheritance for gene: C19orf12 was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.267 CD59 Louise Daugherty Publications for gene: CD59 were set to
Hereditary neuropathy v1.266 CD59 Louise Daugherty Phenotypes for gene: CD59 were changed from to Hemolytic anemia, CD59-mediated, with or without immune-mediated polyneuropathy, 612300; Onset 1st and 2nd decade. Haemolytic anaemia, strokes and relapsing immune-mediated demyelinating neuropathy
Hereditary neuropathy v1.265 CD59 Louise Daugherty Mode of inheritance for gene: CD59 was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.264 COA7 Louise Daugherty Phenotypes for gene: COA7 were changed from to Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3, 618387; Cerebellar atrophy, leukoencephalopathy and spinal cord atrophy in some patients. Axonal sensory and motor neuropathy
Hereditary neuropathy v1.263 COA7 Louise Daugherty Publications for gene: COA7 were set to
Hereditary neuropathy v1.262 COA7 Louise Daugherty Mode of inheritance for gene: COA7 was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.261 CPOX Louise Daugherty Mode of inheritance for gene: CPOX was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy v1.260 CPOX Louise Daugherty Phenotypes for gene: CPOX were changed from to Coproporphyria, 121300; Harderoporphyria, 121300; Skin photosensitivity and haemolytic anaemia. Can present acutely similar to AIP
Hereditary neuropathy v1.259 CPOX Louise Daugherty Mode of inheritance for gene: CPOX was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary neuropathy v1.258 CYP27A1 Louise Daugherty Phenotypes for gene: CYP27A1 were changed from to Cerebrotendinous xanthomatosis, 213700; Adolescent-onset progressive ataxia, myelopathy and dementia, cataracts, low cholesterol, atherosclerosis, xanthomas, soft palate myoclonus, intractable infantile-onset diarrhoea, cerebral white matter lesions on MRI, sensory to motor axonal neuropathy; SNCV described in a minority of patients
Hereditary neuropathy v1.257 CYP27A1 Louise Daugherty Publications for gene: CYP27A1 were set to 22878431
Hereditary neuropathy v1.256 CYP27A1 Louise Daugherty Publications for gene: CYP27A1 were set to 22878431
Hereditary neuropathy v1.256 CYP27A1 Louise Daugherty Publications for gene: CYP27A1 were set to
Hereditary neuropathy v1.255 CYP27A1 Louise Daugherty Mode of inheritance for gene: CYP27A1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.254 DARS2 Louise Daugherty Phenotypes for gene: DARS2 were changed from to Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, 611105; Slowly progressive spasticity, ataxia and dorsal column dysfunction, sensory-motor axonal neuropathy, characteristic MRI findings
Hereditary neuropathy v1.253 DARS2 Louise Daugherty Publications for gene: DARS2 were set to
Hereditary neuropathy v1.252 DARS2 Louise Daugherty Mode of inheritance for gene: DARS2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.251 DEGS1 Louise Daugherty Publications for gene: DEGS1 were set to
Hereditary neuropathy v1.250 DEGS1 Louise Daugherty Phenotypes for gene: DEGS1 were changed from to Leukodystrophy, hypomyelinating, 18, 618404; Demyelinating neuropathy. Motor developmental delay, spasticity, cerebellar atrophy and microcephaly, hypomyelination on MRI, scoliosis, neurogenic bladder, enteral nutrition
Hereditary neuropathy v1.249 DEGS1 Louise Daugherty Mode of inheritance for gene: DEGS1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.248 DGUOK Louise Daugherty Publications for gene: DGUOK were set to
Hereditary neuropathy v1.247 DGUOK Louise Daugherty Phenotypes for gene: DGUOK were changed from to Portal hypertension, noncirrhotic, 617068; Mitochondrial DNA depletion syndrome 3 (hepatocerebral type), 251880; Neonatal liver failure, myopathy, sensory-motor axonal neuropathy
Hereditary neuropathy v1.246 DGUOK Louise Daugherty Mode of inheritance for gene: DGUOK was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.245 DNAJC3 Louise Daugherty Publications for gene: DNAJC3 were set to
Hereditary neuropathy v1.244 DNAJC3 Louise Daugherty Phenotypes for gene: DNAJC3 were changed from to Ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus, 616192; Cerebellar ataxia, neuropathy with SNCV, hearing loss, diabetes mellitus
Hereditary neuropathy v1.243 DNAJC3 Louise Daugherty Mode of inheritance for gene: DNAJC3 was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.242 DSTYK Louise Daugherty Phenotypes for gene: DSTYK were changed from to Spastic paraplegia 23, 270750; Childhood onset spastic paraplegia, prominent skin pigment abnormalities (vitiligo, hyperpigmentation, diffuse lentigines), premature greying of hair, sensory predominant axonal neuropathy (mild).
Hereditary neuropathy v1.241 DSTYK Louise Daugherty Mode of inheritance for gene: DSTYK was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.240 ERBB3 Louise Daugherty Publications for gene: ERBB3 were set to
Hereditary neuropathy v1.239 ERBB3 Louise Daugherty Phenotypes for gene: ERBB3 were changed from to Lethal congenital contractural syndrome 2, 607598; Multiple joint contractures, anterior horn atrophy, death in neonatal period, distended urinary bladder
Hereditary neuropathy v1.238 ERBB3 Louise Daugherty Mode of inheritance for gene: ERBB3 was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.237 ERCC6 Louise Daugherty Phenotypes for gene: ERCC6 were changed from to Cockayne syndrome, type B, 133540; Cockayne syndrome, Dwarfism, optic atrophy, mental retardation, cutaneous photosensitivity, pigmentary retinopathy, deafness, neuropathy with slow conduction velocities
Hereditary neuropathy v1.236 ERCC6 Louise Daugherty Mode of inheritance for gene: ERCC6 was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.235 ERCC8 Louise Daugherty Phenotypes for gene: ERCC8 were changed from to Cockayne syndrome, type A, 216400; Cockayne syndrome, Dwarfism, optic atrophy, mental retardation, cutaneous photosensitivity, pigmentary retinopathy, deafness, neuropathy with slow conduction velocities
Hereditary neuropathy v1.234 ERCC8 Louise Daugherty Mode of inheritance for gene: ERCC8 was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.233 ETFDH Louise Daugherty Phenotypes for gene: ETFDH were changed from to Glutaric acidemia IIC, 231680; Neonatal and late onset forms. hypoglycaemia, metabolic acidosis, and hepatomegaly often preceded by metabolic stress. Muscle involvement in the form of pain, weakness, and lipid storage myopathy also occur. Riboflavin responsive
Hereditary neuropathy v1.232 ETFDH Louise Daugherty Mode of inheritance for gene: ETFDH was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.231 FA2H Louise Daugherty Publications for gene: FA2H were set to
Hereditary neuropathy v1.230 FA2H Louise Daugherty Phenotypes for gene: FA2H were changed from to Spastic paraplegia 35, autosomal recessive, 612319; SPG35, Childhood onset spasticity, cognitive decline and leukodystrophy. Mild sensory axonal neuropathy on NCS. Epilepsy, dysphagia, dysarthria and dystonia also observed
Hereditary neuropathy v1.229 FA2H Louise Daugherty Mode of inheritance for gene: FA2H was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.228 FAH Louise Daugherty Phenotypes for gene: FAH were changed from to Tyrosinemia, type I, 276700; Infantile or adolescent onset liver disease, renal tubular dysfunction and hypophosphatemic rickets. Acute episodes of neuropathy similar to AIP
Hereditary neuropathy v1.227 FAH Louise Daugherty Mode of inheritance for gene: FAH was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.226 FAM126A Louise Daugherty Publications for gene: FAM126A were set to
Hereditary neuropathy v1.225 FAM126A Louise Daugherty Phenotypes for gene: FAM126A were changed from to Leukodystrophy, hypomyelinating, 5, 610532; Congenital cataracts, global developmental delay from 1 year, diffuse cerebral hypomyelination on MRI, neuropathy with SNCV
Hereditary neuropathy v1.224 FAM126A Louise Daugherty Mode of inheritance for gene: FAM126A was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.223 FLVCR1 Louise Daugherty Phenotypes for gene: FLVCR1 were changed from to Ataxia, posterior column, with retinitis pigmentosa, 609033; Retinitis pigmentosa, sensory ganglionopathy and abnormal posterior columns on MRI
Hereditary neuropathy v1.222 FLVCR1 Louise Daugherty Publications for gene: FLVCR1 were set to
Hereditary neuropathy v1.221 FLVCR1 Louise Daugherty Mode of inheritance for gene: FLVCR1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.220 GALC Louise Daugherty Phenotypes for gene: GALC were changed from to Krabbe disease, 245200; Krabbe. Spastic paraplegia, developmental delay, optic atrophy; adult onset has spastic paraplegia and sensory-motor axonal neuropathy with slow or normal conduction velocities, MRI shows leukodystrophy
Hereditary neuropathy v1.219 GALC Louise Daugherty Mode of inheritance for gene: GALC was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.218 GBA2 Louise Daugherty Phenotypes for gene: GBA2 were changed from to Spastic paraplegia 46, autosomal recessive, 614409; SPG46, Spastic paraplegia, cognitive decline, thin corpus callosum, ataxia, cataracts, bulbar dysfunction, axonal sensory-motor neuropathy
Hereditary neuropathy v1.217 GBA2 Louise Daugherty Publications for gene: GBA2 were set to
Hereditary neuropathy v1.216 GBA2 Louise Daugherty Mode of inheritance for gene: GBA2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.215 GJC2 Louise Daugherty Phenotypes for gene: GJC2 were changed from to Spastic paraplegia 44, autosomal recessive, 613206; Leukodystrophy, hypomyelinating, 2, 608804; Infantile-onset Pelizaeus-Merzbacher disease-like phenotype slowly evolving into a form of complicated hereditary spastic paraplegia with mental retardation, dysarthria, optic atrophy andperipheral neuropathyin adulthood. Leukodystrophy
Hereditary neuropathy v1.214 GJC2 Louise Daugherty Mode of inheritance for gene: GJC2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.213 GLE1 Louise Daugherty Phenotypes for gene: GLE1 were changed from to Lethal congenital contracture syndrome 1, 253310; Congenital arthrogryposis with anterior horn cell disease, 611890; Micrognathia, pulmonary hypoplasia, loss of anterior horn cells, intrauterine death
Hereditary neuropathy v1.212 GLE1 Louise Daugherty Publications for gene: GLE1 were set to
Hereditary neuropathy v1.211 GLE1 Louise Daugherty Mode of inheritance for gene: GLE1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.210 HMBS Louise Daugherty Phenotypes for gene: HMBS were changed from to Porphyria, acute intermittent, 176000; AIP, Abdominal pain, psychosis, depression, seizures, axonal predominantly motor neuropathy
Hereditary neuropathy v1.209 HMBS Louise Daugherty Mode of inheritance for gene: HMBS was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy v1.208 IARS2 Louise Daugherty Phenotypes for gene: IARS2 were changed from to Cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia, 616007; Spondyloepiphyseal dysplasia, congenital cataracts, nystagmus, dysmorphic facies, sensory neuronal hearing loss, growth hormone deficiency, sensory axonal peripheral neuropathy
Hereditary neuropathy v1.207 IARS2 Louise Daugherty Publications for gene: IARS2 were set to
Hereditary neuropathy v1.206 IARS2 Louise Daugherty Mode of inheritance for gene: IARS2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.205 KCNA2 Louise Daugherty Phenotypes for gene: KCNA2 were changed from to Epileptic encephalopathy, early infantile, 32, 616366; Childhood onset spasticity, intellectual disability, ataxia, seizures, sensory and motor SNCV in one family
Hereditary neuropathy v1.204 KCNA2 Louise Daugherty Publications for gene: KCNA2 were set to
Hereditary neuropathy v1.203 KCNA2 Louise Daugherty Mode of inheritance for gene: KCNA2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy v1.202 KLC2 Louise Daugherty Phenotypes for gene: KLC2 were changed from to Spastic paraplegia, optic atrophy, and neuropathy, 609541; SPOAN, Early onset spastic paraplegia, congenital optic atrophy, and axonal sensory-motor neuropathy
Hereditary neuropathy v1.201 KLC2 Louise Daugherty Publications for gene: KLC2 were set to
Hereditary neuropathy v1.200 KLC2 Louise Daugherty Mode of inheritance for gene: KLC2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.199 LYST Louise Daugherty Phenotypes for gene: LYST were changed from to Chediak-Higashi syndrome, 214500; Partial albinism, immunodeficiency, cerebellar atrophy, sensory-motor axonal neuropathy
Hereditary neuropathy v1.198 LYST Louise Daugherty Publications for gene: LYST were set to
Hereditary neuropathy v1.197 LYST Louise Daugherty Mode of inheritance for gene: LYST was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.196 MMACHC Louise Daugherty Phenotypes for gene: MMACHC were changed from to Methylmalonic aciduria and homocystinuria, cblC type, 277400; Onset infancy to adulthood; thrombotic thrombocytopenia with encephalopathy, myelopathy, renal and pulmonary complications (can be life threatening), retinitis pigmentosa, axonal motor neuropathy. Treated with high dose vitamin B12
Hereditary neuropathy v1.195 MMACHC Louise Daugherty Publications for gene: MMACHC were set to
Hereditary neuropathy v1.194 MMACHC Louise Daugherty Mode of inheritance for gene: MMACHC was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.193 MT-RNR1 Louise Daugherty Phenotypes for gene: MT-RNR1 were changed from to Parkinsonism, deafness, and sensory-motor axonal neuropathy
Hereditary neuropathy v1.192 MT-TL1 Louise Daugherty Phenotypes for gene: MT-TL1 were changed from to Myopathy, deafness, ophthalmoplegia, diabetes, stroke like episodes, predominantly sensory axonal neuropathy
Hereditary neuropathy v1.191 NAGA Louise Daugherty Phenotypes for gene: NAGA were changed from to Kanzaki disease, 609242; Kanzaki disease. Adult onset diffuse angiokeratoma, sensory-neural hearing loss, recurrent episodes of vertigo, sensory-motor axonal neuropathy. Periventricular white matter abnormalities on MRI
Hereditary neuropathy v1.190 NAGA Louise Daugherty Publications for gene: NAGA were set to
Hereditary neuropathy v1.189 NAGA Louise Daugherty Mode of inheritance for gene: NAGA was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.188 OPA1 Louise Daugherty Phenotypes for gene: OPA1 were changed from to Optic atrophy 1, 165500; Optic atrophy plus syndrome, 125250; Optic neuropathy, PEO, deafness, myelopathy, sensory-motor axonal neuropathy
Hereditary neuropathy v1.187 OPA1 Louise Daugherty Mode of inheritance for gene: OPA1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy v1.186 OPA3 Louise Daugherty Phenotypes for gene: OPA3 were changed from to Optic atrophy 3 with cataract, 165300; 3-methylglutaconic aciduria, type III, 258501; Infantile optic atrophy, additionally, extra pyramidal disorder (chorea), ataxia, cognitive defects, axonal sensory neuropathy, autonomic neuropathy, pseudo-obstruction
Hereditary neuropathy v1.185 OPA3 Louise Daugherty Mode of inheritance for gene: OPA3 was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary neuropathy v1.184 PDYN Louise Daugherty Phenotypes for gene: PDYN were changed from to Spinocerebellar ataxia 23, 610245; Cerebellar ataxia, sensory-motor axonal neuropathy
Hereditary neuropathy v1.183 PDYN Louise Daugherty Publications for gene: PDYN were set to
Hereditary neuropathy v1.182 PDYN Louise Daugherty Mode of inheritance for gene: PDYN was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy v1.181 PEX10 Louise Daugherty Phenotypes for gene: PEX10 were changed from to Failure to thrive, facial dismorphism, agenesis of the corpus callosum, death in first year of life, axonal motor neuropathy, progressive ataxia and sensory-motor axonal neuropathy in adulthood described; Peroxisome biogenesis disorder 6A (Zellweger), 614870; Peroxisome biogenesis disorder 6B, 614871
Hereditary neuropathy v1.180 PEX10 Louise Daugherty Publications for gene: PEX10 were set to
Hereditary neuropathy v1.179 PMM2 Louise Daugherty Phenotypes for gene: PMM2 were changed from to Congenital disorder of glycosylation, type Ia, 212065; Neonatal onset, leukodystrophy, abnormal serum glycoproteins, mental retardation, hypotonia, ataxia, retinitis pigmentosa, seizures, slowly progressive neuropathy with SNCV, severe infections, hepatic insufficiency and cardiomyopathy
Hereditary neuropathy v1.178 PMM2 Louise Daugherty Publications for gene: PMM2 were set to
Hereditary neuropathy v1.177 PMM2 Louise Daugherty Mode of inheritance for gene: PMM2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.176 PNKP Louise Daugherty Phenotypes for gene: PNKP were changed from to Ataxia-oculomotor apraxia 4, 616267; Microcephaly, seizures, and developmental delay, 613402; Microcephaly, global developmental delay, progressive cerebellar ataxia and atrophy, sensory-motor axonal neuropathy
Hereditary neuropathy v1.175 PNKP Louise Daugherty Publications for gene: PNKP were set to
Hereditary neuropathy v1.174 PNKP Louise Daugherty Mode of inheritance for gene: PNKP was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.173 POLR3A Louise Daugherty Phenotypes for gene: POLR3A were changed from Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism, 607694; Adolescent onset progressive spastic ataxia, tremor, involvement of central sensory tracts, dental complications to Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism, 607694; Adolescent onset progressive spastic ataxia, tremor, involvement of central sensory tracts, dental complications; Bilateral hyperintensities on MRI from the superior cerebellar peduncle to the dentate nucleus / midbrain
Hereditary neuropathy v1.172 POLR3A Louise Daugherty Phenotypes for gene: POLR3A were changed from Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism, 607694 to Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism, 607694; Adolescent onset progressive spastic ataxia, tremor, involvement of central sensory tracts, dental complications
Hereditary neuropathy v1.171 POLR3A Louise Daugherty Phenotypes for gene: POLR3A were changed from test to Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism, 607694
Hereditary neuropathy v1.170 POLR3A Louise Daugherty Phenotypes for gene: POLR3A were changed from to test
Hereditary neuropathy v1.170 POLR3A Louise Daugherty Phenotypes for gene: POLR3A were changed from to test
Hereditary neuropathy v1.169 POLR3A Louise Daugherty Publications for gene: POLR3A were set to
Hereditary neuropathy v1.168 POLR3A Louise Daugherty Mode of inheritance for gene: POLR3A was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.167 PPOX Louise Daugherty Phenotypes for gene: PPOX were changed from to Porphyria variegata, 176200; Skin photosensitivity. Acute episodes similar to AIP
Hereditary neuropathy v1.166 PPOX Louise Daugherty Mode of inheritance for gene: PPOX was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy v1.165 PRKCG Louise Daugherty Phenotypes for gene: PRKCG were changed from Hereditary Neuropathies to Hereditary Neuropathies; Usually adult onset isolated cerebellar ataxia. Missense mutation in catalytic domain of exon 11 associated with complex syndrome including cerebellar ataxia, sensory motor axonal neuropathy, parkinsonism, dystonia, myoclonus and pyramidal syndrome; Spinocerebellar ataxia 14, 605361
Hereditary neuropathy v1.164 PRKCG Louise Daugherty Publications for gene: PRKCG were set to 26633542
Hereditary neuropathy v1.163 PRKCG Louise Daugherty Mode of inheritance for gene: PRKCG was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy v1.162 PTEN Louise Daugherty Phenotypes for gene: PTEN were changed from multifocal demyelinating motor neuropathy, macrocephaly, autism spectrum disorder and skin hamartomas to Cowden syndrome 1, 158350; multifocal demyelinating motor neuropathy, macrocephaly, autism spectrum disorder and skin hamartomas
Hereditary neuropathy v1.161 PTEN Louise Daugherty Phenotypes for gene: PTEN were changed from to multifocal demyelinating motor neuropathy, macrocephaly, autism spectrum disorder and skin hamartomas
Hereditary neuropathy v1.160 PTEN Louise Daugherty Mode of inheritance for gene: PTEN was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy v1.159 PTRH2 Louise Daugherty Publications for gene: PTRH2 were set to
Hereditary neuropathy v1.158 PTRH2 Louise Daugherty Phenotypes for gene: PTRH2 were changed from to Infantile-onset multisystem neurologic, endocrine, and pancreatic disease, 616263; Infantile-onset multisystem disease with intellectual disability, microcephaly, progressive ataxia, sensory neuronal hearing loss, hepatomegaly, pancreatic insufficiency, proximal placement of thumb, SNCV neuropathy
Hereditary neuropathy v1.157 PTRH2 Louise Daugherty Mode of inheritance for gene: PTRH2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.156 SCARB2 Louise Daugherty Phenotypes for gene: SCARB2 were changed from to Epilepsy, progressive myoclonic 4, with or without renal failure, 254900; Progressive myoclonic epilepsy with preserved cognition, onset 2nd decade, renal impairment, rarely demyelinating sensory-motor neuropathy (without renal failure)
Hereditary neuropathy v1.155 SCARB2 Louise Daugherty Publications for gene: SCARB2 were set to
Hereditary neuropathy v1.154 SCARB2 Louise Daugherty Mode of inheritance for gene: SCARB2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.153 SCP2 Louise Daugherty Phenotypes for gene: SCP2 were changed from to Leukoencephalopathy with dystonia and motor neuropathy, 613724; Dystonia, hyposmia, azoospermia, motor predominant axonal neuropathy, bilateral thalamic T2 high signal on MRI
Hereditary neuropathy v1.152 SCP2 Louise Daugherty Publications for gene: SCP2 were set to
Hereditary neuropathy v1.151 SCP2 Louise Daugherty Mode of inheritance for gene: SCP2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.150 SCYL1 Louise Daugherty Phenotypes for gene: SCYL1 were changed from to Spinocerebellar ataxia, autosomal recessive 21, 616719; Early onset ataxia (<1 yr) with recurrent episodes of liver failure, sensory-motor axonal neuropathy, cerebellar atrophy
Hereditary neuropathy v1.149 SCYL1 Louise Daugherty Publications for gene: SCYL1 were set to
Hereditary neuropathy v1.148 SCYL1 Louise Daugherty Mode of inheritance for gene: SCYL1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.147 SELENOI Louise Daugherty Phenotypes for gene: SELENOI were changed from to Infantile onset, global developmental delay, spasticity, periventricular white mater signal change on MRI, peripheral neuropathy with SNCV. Seizures and bifid uvula in some affected individuals
Hereditary neuropathy v1.146 SELENOI Louise Daugherty Mode of inheritance for gene: SELENOI was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.145 SLC25A19 Louise Daugherty Phenotypes for gene: SLC25A19 were changed from to Thiamine metabolism dysfunction syndrome 4 (progressive polyneuropathy type), 613710; Acute encephalopathic episodes and paralysis following febrile illness with almost complete recovery. Absent sensory-motor action potential during illness. Bilateral striatal necrosis on MRI. Additional chronic progressive axonal neuropathy
Hereditary neuropathy v1.144 SLC25A19 Louise Daugherty Publications for gene: SLC25A19 were set to
Hereditary neuropathy v1.143 SLC25A19 Louise Daugherty Mode of inheritance for gene: SLC25A19 was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.142 SLC25A46 Louise Daugherty Phenotypes for gene: SLC25A46 were changed from Optic atrophy and progressive visual loss in the 1st decade, then spasticity, cerebellar ataxia, sensory-motor axonal neuropathy to Neuropathy, hereditary motor and sensory, type VIB, 616505; Optic atrophy and progressive visual loss in the 1st decade, then spasticity, cerebellar ataxia, sensory-motor axonal neuropathy
Hereditary neuropathy v1.141 SLC25A46 Louise Daugherty Phenotypes for gene: SLC25A46 were changed from to Optic atrophy and progressive visual loss in the 1st decade, then spasticity, cerebellar ataxia, sensory-motor axonal neuropathy
Hereditary neuropathy v1.140 SLC25A46 Louise Daugherty Publications for gene: SLC25A46 were set to
Hereditary neuropathy v1.139 SLC25A46 Louise Daugherty Mode of inheritance for gene: SLC25A46 was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.138 SUCLA2 Louise Daugherty Phenotypes for gene: SUCLA2 were changed from to Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria), 612073; Leigh like syndrome, deafness, progressive dystonia, mild methylmaolic acidaemia
Hereditary neuropathy v1.137 SUCLA2 Louise Daugherty Publications for gene: SUCLA2 were set to
Hereditary neuropathy v1.136 SUCLA2 Louise Daugherty Mode of inheritance for gene: SUCLA2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.135 VPS13A Louise Daugherty Phenotypes for gene: VPS13A were changed from Choreoacanthocytosis. Onset 3rd to 5th decade, red cell acanthocytosis and progressive neurodegeneration, seizures, dysarthria, chorea, orofacial dyskinesia, psychiatric disturbance, axonal sensory-motor neuropathy, raised CK to Choreoacanthocytosis, 200150; Choreoacanthocytosis. Onset 3rd to 5th decade, red cell acanthocytosis and progressive neurodegeneration, seizures, dysarthria, chorea, orofacial dyskinesia, psychiatric disturbance, axonal sensory-motor neuropathy, raised CK
Hereditary neuropathy v1.134 XK Louise Daugherty Phenotypes for gene: XK were changed from Mceod syndrome, Onset 25-60, acanthocytes and Huntington-like syndrome, also epilepsy, cardiomyopathy, axonal motor neuropathy to McLeod syndrome with or without chronic granulomatous disease, 300842; Mceod syndrome, Onset 25-60, acanthocytes and Huntington-like syndrome, also epilepsy, cardiomyopathy, axonal motor neuropathy
Hereditary neuropathy v1.133 XPA Louise Daugherty Phenotypes for gene: XPA were changed from Photosensitivity and increased risk of cutaneous malignancy, global developmental delay, deafness, sensory-motor axonal peripheral neuropathy to Xeroderma pigmentosum, group A, 278700; Photosensitivity and increased risk of cutaneous malignancy, global developmental delay, deafness, sensory-motor axonal peripheral neuropathy
Hereditary neuropathy v1.132 XPA Louise Daugherty Mode of inheritance for gene: XPA was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.131 XRCC1 Louise Daugherty Phenotypes for gene: XRCC1 were changed from Ataxia, developmental delay, azoospermia and hypogonadism, myotonia, sensory and motor axonal neuropathy to Spinocerebellar ataxia, autosomal recessive 26, 617633; Ataxia, developmental delay, azoospermia and hypogonadism, myotonia, sensory and motor axonal neuropathy
Hereditary neuropathy v1.130 VPS13A Louise Daugherty Phenotypes for gene: VPS13A were changed from to Choreoacanthocytosis. Onset 3rd to 5th decade, red cell acanthocytosis and progressive neurodegeneration, seizures, dysarthria, chorea, orofacial dyskinesia, psychiatric disturbance, axonal sensory-motor neuropathy, raised CK
Hereditary neuropathy v1.129 VPS13A Louise Daugherty Mode of inheritance for gene: VPS13A was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.128 XK Louise Daugherty Phenotypes for gene: XK were changed from to Mceod syndrome, Onset 25-60, acanthocytes and Huntington-like syndrome, also epilepsy, cardiomyopathy, axonal motor neuropathy
Hereditary neuropathy v1.127 XK Louise Daugherty Mode of inheritance for gene: XK was changed from to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Hereditary neuropathy v1.126 XPA Louise Daugherty Phenotypes for gene: XPA were changed from to Photosensitivity and increased risk of cutaneous malignancy, global developmental delay, deafness, sensory-motor axonal peripheral neuropathy
Hereditary neuropathy v1.125 XPA Louise Daugherty Publications for gene: XPA were set to
Hereditary neuropathy v1.125 XPA Louise Daugherty Publications for gene: XPA were set to
Hereditary neuropathy v1.124 XRCC1 Louise Daugherty Phenotypes for gene: XRCC1 were changed from to Ataxia, developmental delay, azoospermia and hypogonadism, myotonia, sensory and motor axonal neuropathy
Hereditary neuropathy v1.123 XRCC1 Louise Daugherty Publications for gene: XRCC1 were set to
Hereditary neuropathy v1.122 XRCC1 Louise Daugherty Mode of inheritance for gene: XRCC1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 XRCC1 Alexander Rossor reviewed gene: XRCC1: Rating: GREEN; Mode of pathogenicity: ; Publications: 29472272, 28002403; Phenotypes: Ataxia, developmental delay, azoospermia and hypogonadism, myotonia, sensory and motor axonal neuropathy.; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 XPA Alexander Rossor reviewed gene: XPA: Rating: GREEN; Mode of pathogenicity: ; Publications: 2168777; Phenotypes: Photosensitivity and increased risk of cutaneous malignancy, global developmental delay, deafness, sensory-motor axonal peripheral neuropathy.; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 XK Alexander Rossor reviewed gene: XK: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Mceod syndrome, Onset 25-60, acanthocytes and Huntington-like syndrome, also epilepsy, cardiomyopathy, axonal motor neuropathy; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Hereditary neuropathy v1.121 VPS13A Alexander Rossor reviewed gene: VPS13A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Choreoacanthocytosis. Onset 3rd to 5th decade, red cell acanthocytosis and progressive neurodegeneration, seizures, dysarthria, chorea, orofacial dyskinesia, psychiatric disturbance, axonal sensory-motor neuropathy, raised CK; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 SUCLA2 Alexander Rossor reviewed gene: SUCLA2: Rating: AMBER; Mode of pathogenicity: ; Publications: 17287286; Phenotypes: Leigh like syndrome, deafness, progressive dystonia, mild methylmaolic acidaemia.; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 SLC25A46 Alexander Rossor reviewed gene: SLC25A46: Rating: GREEN; Mode of pathogenicity: ; Publications: 26168012; Phenotypes: Optic atrophy and progressive visual loss in the 1st decade, then spasticity, cerebellar ataxia, sensory-motor axonal neuropathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 SLC25A19 Alexander Rossor reviewed gene: SLC25A19: Rating: GREEN; Mode of pathogenicity: ; Publications: 19798730; Phenotypes: Acute encephalopathic episodes and paralysis following febrile illness with almost complete recovery. Absent sensory-motor action potential during illness. Bilateral striatal necrosis on MRI. Additional chronic progressive axonal neuropathy ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 SELENOI Alexander Rossor reviewed gene: SELENOI: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Infantile onset, global developmental delay, spasticity, periventricular white mater signal change on MRI, peripheral neuropathy with SNCV. Seizures and bifid uvula in some affected individuals; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 SCYL1 Alexander Rossor reviewed gene: SCYL1: Rating: GREEN; Mode of pathogenicity: ; Publications: 26581903; Phenotypes: Early onset ataxia (<1 yr) with recurrent episodes of liver failure, sensory-motor axonal neuropathy, cerebellar atrophy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 SCP2 Alexander Rossor reviewed gene: SCP2: Rating: RED; Mode of pathogenicity: ; Publications: 16685654; Phenotypes: Dystonia, hyposmia, azoospermia, motor predominant axonal neuropathy, bilateral thalamic T2 high signal on MRI; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 SCARB2 Alexander Rossor reviewed gene: SCARB2: Rating: GREEN; Mode of pathogenicity: ; Publications: 21670406, 19597094; Phenotypes: Progressive myoclonic epilepsy with preserved cognition, onset 2nd decade, renal impairment, rarely demyelinating sensory-motor neuropathy (without renal failure); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 PTRH2 Alexander Rossor reviewed gene: PTRH2: Rating: AMBER; Mode of pathogenicity: ; Publications: 25572476, 25558065; Phenotypes: Infantile-onset multisystem disease with intellectual disability, microcephaly, progressive ataxia, sensory neuronal hearing loss, hepatomegaly, pancreatic insufficiency, proximal placement of thumb, SNCV neuropathy.; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 PTEN Alexander Rossor reviewed gene: PTEN: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: multifocal demyelinating motor neuropathy, macrocephaly, autism spectrum disorder and skin hamartomas; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy v1.121 PRKCG Alexander Rossor edited their review of gene: PRKCG: Added comment: Neuropathy rare feature; Changed rating: GREEN; Changed phenotypes: Usually adult onset isolated cerebellar ataxia. Missense mutation in catalytic domain of exon 11 associated with complex syndrome including cerebellar ataxia, sensory motor axonal neuropathy, parkinsonism, dystonia, myoclonus and pyramidal syndrome.
Hereditary neuropathy v1.121 PPOX Alexander Rossor reviewed gene: PPOX: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Skin photosensitivity. Acute episodes similar to AIP.; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy v1.121 POLR3A Alexander Rossor reviewed gene: POLR3A: Rating: GREEN; Mode of pathogenicity: ; Publications: 28459997; Phenotypes: Adolescent onset progressive spastic ataxia, tremor, involvement of central sensory tracts, dental complications (hypodontia, severe peridontal disease. Bilateral hyperintensities on MRI from the superior cerebellar peduncle to the dentate nucleus / midbrain. Abnormal nerve conduction in 8 out of 14 cases.; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 PNKP Alexander Rossor reviewed gene: PNKP: Rating: GREEN; Mode of pathogenicity: ; Publications: 30039206; Phenotypes: Microcephaly, global developmental delay, progressive cerebellar ataxia and atrophy, sensory-motor axonal neuropathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 PMM2 Alexander Rossor reviewed gene: PMM2: Rating: GREEN; Mode of pathogenicity: ; Publications: 9140401; Phenotypes: Neonatal onset, leukodystrophy, abnormal serum glycoproteins, mental retardation, hypotonia, ataxia, retinitis pigmentosa, seizures, slowly progressive neuropathy with SNCV, severe infections, hepatic insufficiency and cardiomyopathy. ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 PEX10 Alexander Rossor reviewed gene: PEX10: Rating: GREEN; Mode of pathogenicity: ; Publications: 27230853, 20695019; Phenotypes: Failure to thrive, facial dismorphism, agenesis of the corpus callosum, death in first year of life, axonal motor neuropathy, progressive ataxia and sensory-motor axonal neuropathy in adulthood described; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 PDYN Alexander Rossor reviewed gene: PDYN: Rating: GREEN; Mode of pathogenicity: ; Publications: 21035104; Phenotypes: Cerebellar ataxia, sensory-motor axonal neuropathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy v1.121 OPA3 Alexander Rossor reviewed gene: OPA3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Infantile optic atrophy, additionally, extra pyramidal disorder (chorea), ataxia, cognitive defects, axonal sensory neuropathy, autonomic neuropathy, pseudo-obstruction; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 OPA1 Alexander Rossor reviewed gene: OPA1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Optic neuropathy, PEO, deafness, myelopathy, sensory-motor axonal neuropathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy v1.121 NAGA Alexander Rossor reviewed gene: NAGA: Rating: GREEN; Mode of pathogenicity: ; Publications: 15136691; Phenotypes: Kanzaki disease. Adult onset diffuse angiokeratoma, sensory-neural hearing loss, recurrent episodes of vertigo, sensory-motor axonal neuropathy. Periventricular white matter abnormalities on MRI.; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 MT-TL1 Alexander Rossor reviewed gene: MT-TL1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Myopathy, deafness, ophthalmoplegia, diabetes, stroke like episodes, predominantly sensory axonal neuropathy; Mode of inheritance: MITOCHONDRIAL
Hereditary neuropathy v1.121 MT-RNR1 Alexander Rossor reviewed gene: MT-RNR1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Parkinsonism, deafness, and sensory-motor axonal neuropathy; Mode of inheritance: MITOCHONDRIAL
Hereditary neuropathy v1.121 MMACHC Alexander Rossor reviewed gene: MMACHC: Rating: GREEN; Mode of pathogenicity: ; Publications: 20610126; Phenotypes: Onset infancy to adulthood, thrombotic thrombocytopenia with encephalopathy, myelopathy, renal and pulmonary complications (can be life threatening), retinitis pigmentosa, axonal motor neuropathy. Treated with high dose vitamin B12.; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 LYST Alexander Rossor reviewed gene: LYST: Rating: GREEN; Mode of pathogenicity: ; Publications: 27669550; Phenotypes: Partial albinism, immunodeficiency, cerebellar atrophy, sensory-motor axonal neuropathy.; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 KLC2 Alexander Rossor reviewed gene: KLC2: Rating: AMBER; Mode of pathogenicity: ; Publications: 26385635; Phenotypes: SPOAN, Early onset spastic paraplegia, congenital optic atrophy, and axonal sensory-motor neuropathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 KCNA2 Alexander Rossor reviewed gene: KCNA2: Rating: GREEN; Mode of pathogenicity: ; Publications: 27543892; Phenotypes: Childhood onset spasticity, intellectual disability, ataxia, seizures, sensory and motor SNCV in one family; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy v1.121 IARS2 Alexander Rossor reviewed gene: IARS2: Rating: GREEN; Mode of pathogenicity: ; Publications: 25130867, 28328135, 30041933, 30419932; Phenotypes: Spondyloepiphyseal dysplasia, congenital cataracts, nystagmus, dysmorphic facies, sensory neuronal hearing loss, growth hormone deficiency, sensory axonal peripheral neuropathy.; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 HMBS Alexander Rossor reviewed gene: HMBS: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: AIP, Abdominal pain, psychosis, depression, seizures, axonal predominantly motor neuropathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy v1.121 GLE1 Alexander Rossor reviewed gene: GLE1: Rating: AMBER; Mode of pathogenicity: ; Publications: 18204449; Phenotypes: Micrognathia, pulmonary hypoplasia, loss of anterior horn cells, intrauterine death.; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 GJC2 Alexander Rossor reviewed gene: GJC2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: Infantile-onset Pelizaeus-Merzbacher disease-like phenotype slowly evolving into a form of complicated hereditary spastic paraplegia with mental retardation, dysarthria, optic atrophy andperipheral neuropathyin adulthood. Leukodystrophy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 GBA2 Alexander Rossor reviewed gene: GBA2: Rating: GREEN; Mode of pathogenicity: ; Publications: 23332916; Phenotypes: SPG46, Spastic paraplegia, cognitive decline, thin corpus callosum, ataxia, cataracts, bulbar dysfunction, axonal sensory-motor neuropathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 GALC Alexander Rossor reviewed gene: GALC: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Krabbe. Spastic paraplegia, developmental delay, optic atrophy, adult onset has spastic paraplegia and sensory-motor axonal neuropathy with slow or normal conduction velocities, MRI shows leukodystrophy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 FLVCR1 Alexander Rossor reviewed gene: FLVCR1: Rating: GREEN; Mode of pathogenicity: ; Publications: 21070897; Phenotypes: Retinitis pigmentosa, sensory ganglionopathy and abnormal posterior columns on MRI; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 FAM126A Alexander Rossor reviewed gene: FAM126A: Rating: GREEN; Mode of pathogenicity: ; Publications: 16951682; Phenotypes: Congenital cataracts, global developmental delay from 1 year, diffuse cerebral hypomyelination on MRI, neuropathy with SNCV; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 FAH Alexander Rossor reviewed gene: FAH: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Infantile or adolescent onset liver disease, renal tubular dysfunction and hypophosphatemic rickets. Acute episodes of neuropathy similar to AIP.; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 FA2H Alexander Rossor reviewed gene: FA2H: Rating: AMBER; Mode of pathogenicity: ; Publications: 22146942; Phenotypes: SPG35, Childhood onset spasticity, cognitive decline and leukodystrophy. Mild sensory axonal neuropathy on NCS. Epilepsy, dysphagia, dysarthria and dystonia also observed.; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 ETFDH Alexander Rossor reviewed gene: ETFDH: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Neonatal and late onset forms. hypoglycaemia, metabolic acidosis, and hepatomegaly often preceded by metabolic stress. Muscle involvement in the form of pain, weakness, and lipid storage myopathy also occur. Riboflavin responsive.; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 ERCC8 Alexander Rossor reviewed gene: ERCC8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Cockayne syndrome, Dwarfism, optic atrophy, mental retardation, cutaneous photosensitivity, pigmentary retinopathy, deafness, neuropathy with slow conduction velocities; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 ERCC6 Alexander Rossor reviewed gene: ERCC6: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Cockayne syndrome, Dwarfism, optic atrophy, mental retardation, cutaneous photosensitivity, pigmentary retinopathy, deafness, neuropathy with slow conduction velocities; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 ERBB3 Alexander Rossor reviewed gene: ERBB3: Rating: AMBER; Mode of pathogenicity: ; Publications: 17709104; Phenotypes: Multiple joint contractures,, anterior horn atrophy, death in neonatal period, distended urinary bladder; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 DSTYK Alexander Rossor reviewed gene: DSTYK: Rating: RED; Mode of pathogenicity: ; Publications: 28157540; Phenotypes: Childhood onset spastic paraplegia, prominent skin pigment abnormalities (vitiligo, hyperpigmentation, diffuse lentigines), premature greying of hair, sensory predominant axonal neuropathy (mild).; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 DNAJC3 Alexander Rossor reviewed gene: DNAJC3: Rating: GREEN; Mode of pathogenicity: ; Publications: 25466870; Phenotypes: Cerebellar ataxia, neuropathy with SNCV, hearing loss, diabetes mellitus; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 DGUOK Alexander Rossor reviewed gene: DGUOK: Rating: AMBER; Mode of pathogenicity: ; Publications: 15883261; Phenotypes: Neonatal liver failure, myopathy, sensory-motor axonal neuropathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 DEGS1 Alexander Rossor reviewed gene: DEGS1: Rating: GREEN; Mode of pathogenicity: ; Publications: 30620338, 30620337; Phenotypes: Demyelinating neuropathy. Motor developmental delay, spasticity, cerebellar atrophy and microcephaly, hypomyelination on MRI, scoliosis, neurogenic bladder, enteral nutrition.; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 DARS2 Alexander Rossor reviewed gene: DARS2: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938; Phenotypes: Slowly progressive spasticity, ataxia and dorsal column dysfunction, sensory-motor axonal neuropathy, characteristic MRI findings ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 CYP27A1 Alexander Rossor reviewed gene: CYP27A1: Rating: GREEN; Mode of pathogenicity: ; Publications: 22878431; Phenotypes: Cerebrotendinous Xanthomatosis. Adolescent-onset progressive ataxia, myelopathy and dementia, cataracts, low cholesterol, atherosclerosis, xanthomas, soft palate myoclonus, intractable infantile-onset diarrhoea, cerebral white matter lesions on MRI, sensory>motor axonal neuropathy, SNCV described in a minority of patients; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 CPOX Alexander Rossor reviewed gene: CPOX: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Skin photosensitivity and haemolytic anaemia. Can present acutely similar to AIP; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy v1.121 COA7 Alexander Rossor reviewed gene: COA7: Rating: GREEN; Mode of pathogenicity: ; Publications: 29718187; Phenotypes: Cerebellar atrophy, leukoencephalopathy and spinal cord atrophy in some patients. Axonal sensory and motor neuropathy.; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 CD59 Alexander Rossor reviewed gene: CD59: Rating: GREEN; Mode of pathogenicity: ; Publications: 23149847, 24382084; Phenotypes: Onset 1st and 2nd decade. Haemolytic anaemia, strokes and relapsing immune-mediated demyelinating neuropathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 C19orf12 Alexander Rossor reviewed gene: C19orf12: Rating: AMBER; Mode of pathogenicity: ; Publications: 20039086, 23857908; Phenotypes: SPG43, Childhood onset spastic paraplegia and sensory-motor axonal neuropathy, NBIA with optic atrophy, extrapyramidal signs; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 BCKDHB Alexander Rossor reviewed gene: BCKDHB: Rating: GREEN; Mode of pathogenicity: ; Publications: 18855118, 11180212; Phenotypes: Maple Syrup Urine Disease, Metabolic encephalopathy, elevated branched chain amino acids in urine, acute axonal neuropathy ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 B4GALNT1 Alexander Rossor reviewed gene: B4GALNT1: Rating: GREEN; Mode of pathogenicity: ; Publications: 23746551; Phenotypes: SPG26, Spastic paraplegia, intellectual disability, ataxia, dystonia, axonal sensory-motor neuropathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 ARSA Alexander Rossor reviewed gene: ARSA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Metachromatic leukodystrophy. Severe late infantile form with mental retardation and severe course. Regression before 30 months, adult onset, psychiatric symptoms, leukodystrophy on MRI, progressive neuropathy with SNCV, optic atrophy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 ARL6IP1 Alexander Rossor reviewed gene: ARL6IP1: Rating: RED; Mode of pathogenicity: ; Publications: 24482476; Phenotypes: Childhood onset spastic paraplegia with mutilating, sensory>motor axonal neuropathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 APOA1 Alexander Rossor reviewed gene: APOA1: Rating: GREEN; Mode of pathogenicity: ; Publications: 23730806; Phenotypes: Renal failure, Axonal sensory-motor neuropathy similar to TTR FAP, amyloid nephropathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy v1.121 AP1S1 Alexander Rossor reviewed gene: AP1S1: Rating: GREEN; Mode of pathogenicity: ; Publications: 19057675; Phenotypes: Congenital onset, Mental retardation, Enteropathy (severe congenital diarrhoea), Deafness, sensory-motor Neuropathy with intermediate conduction velocities, Ichthyosis, Keratoderma; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 AGXT Alexander Rossor reviewed gene: AGXT: Rating: GREEN; Mode of pathogenicity: ; Publications: 4701948, 25363903; Phenotypes: Renal failure and deposition of calcium oxalate crystals in tissues including nerve and muscle. Sensory and motor axonal neuropathy (some slowing); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 AGTPBP1 Alexander Rossor reviewed gene: AGTPBP1: Rating: GREEN; Mode of pathogenicity: ; Publications: 30420557; Phenotypes: Early onset cerebellar atrophy, developmental delay, and feeding and respiratory difficulties, severe motor neuronopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 ABHD12 Alexander Rossor reviewed gene: ABHD12: Rating: GREEN; Mode of pathogenicity: ; Publications: 29571850, 20797687; Phenotypes: Onset 2nd decade, neuropathy with SNCV, sensory neuronal hearing loss, retinitis pigmentosa, spastic paraplegia, ataxia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.121 ABCA1 Alexander Rossor reviewed gene: ABCA1: Rating: GREEN; Mode of pathogenicity: ; Publications: 29582519; Phenotypes: Tangier disease. Multifocal relapsing mononeuropathies. Orange tonsils, organomegaly, pain, paresthesias, anaesthesia.; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v1.53 BCORL1 Rebecca Foulger gene: BCORL1 was added
gene: BCORL1 was added to Genetic epilepsy syndromes. Sources: Literature
Mode of inheritance for gene: BCORL1 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: BCORL1 were set to 30941876
Phenotypes for gene: BCORL1 were set to Intellectual disability and seizures
Added comment: Added BCORL1 to the Genetic epilepsy syndromes panel as a Red gene based on a 2019 paper by Shukla et al (PMID:30941876) who report 5 males from 3 families with ASD, ID/DD and dysmorphic features. Three siblings (patients 3, 4 and 5) had Seizures (at 1 year, 2 year and 6 months of age, respectively). Patients 1 and 2 did not have seizures but their ID/DD phenotype was less severe than those of the three brothers. Therefore currently only one family and a Red rating.
Sources: Literature
Hereditary neuropathy v1.120 ZFYVE26 Louise Daugherty Source London North GLH was added to ZFYVE26.
Hereditary neuropathy v1.120 VRK1 Louise Daugherty Source London North GLH was added to VRK1.
Hereditary neuropathy v1.120 TWNK Louise Daugherty Source London North GLH was added to TWNK.
Hereditary neuropathy v1.120 TTPA Louise Daugherty Source London North GLH was added to TTPA.
Hereditary neuropathy v1.120 SPG7 Louise Daugherty Source London North GLH was added to SPG7.
Hereditary neuropathy v1.120 SOX10 Louise Daugherty Source London North GLH was added to SOX10.
Hereditary neuropathy v1.120 PTPN11 Louise Daugherty Source London North GLH was added to PTPN11.
Hereditary neuropathy v1.120 PRKCG Louise Daugherty Source London North GLH was added to PRKCG.
Hereditary neuropathy v1.120 PNPLA6 Louise Daugherty Source London North GLH was added to PNPLA6.
Hereditary neuropathy v1.120 PLP1 Louise Daugherty Source London North GLH was added to PLP1.
Hereditary neuropathy v1.120 PDK3 Louise Daugherty Source London North GLH was added to PDK3.
Hereditary neuropathy v1.120 MYH14 Louise Daugherty Source London North GLH was added to MYH14.
Hereditary neuropathy v1.120 MTTP Louise Daugherty Source London North GLH was added to MTTP.
Hereditary neuropathy v1.120 HADHB Louise Daugherty Source London North GLH was added to HADHB.
Hereditary neuropathy v1.120 HADHA Louise Daugherty Source London North GLH was added to HADHA.
Hereditary neuropathy v1.120 DST Louise Daugherty Source London North GLH was added to DST.
Hereditary neuropathy v1.120 DRP2 Louise Daugherty Source London North GLH was added to DRP2.
Intellectual disability v2.857 BCORL1 Rebecca Foulger Tag watchlist tag was added to gene: BCORL1.
Intellectual disability v2.857 BCORL1 Rebecca Foulger Classified gene: BCORL1 as Amber List (moderate evidence)
Intellectual disability v2.857 BCORL1 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Red to Amber based on external review by Konstantinos Varvagiannis and the new paper Shukla et al., 2019 (PMID:30941876). The original Asn820Ser variant from Schuurs-Hoeijmakers et al., 2013 (PMID:24123876) is still listed as a VUS in OMIM due to a lack of evidence for association with the ID phenotype. Although Shukla et al report 3 cases with 3 new BCORL1 variants (two unrelated males and a further three brothers), patient 2 does not have ID, but instead has typical early motor milestones, and speech delay. ID is also mild in Patient 1. Based on 2 clear cases plus 1 potential case from Shukla et al,. I have rated Amber and added a 'watchlist' tag awaiting further reports.
Intellectual disability v2.857 BCORL1 Rebecca Foulger Gene: bcorl1 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy v1.119 SELENOI Louise Daugherty Source NHS GMS was added to SELENOI.
Hereditary neuropathy v1.119 SCP2 Louise Daugherty Source NHS GMS was added to SCP2.
Hereditary neuropathy v1.119 DSTYK Louise Daugherty Source NHS GMS was added to DSTYK.
Hereditary neuropathy v1.119 ARL6IP1 Louise Daugherty Source NHS GMS was added to ARL6IP1.
Hereditary neuropathy v1.119 SUCLA2 Louise Daugherty Source NHS GMS was added to SUCLA2.
Hereditary neuropathy v1.119 PTRH2 Louise Daugherty Source NHS GMS was added to PTRH2.
Hereditary neuropathy v1.119 KLC2 Louise Daugherty Source NHS GMS was added to KLC2.
Hereditary neuropathy v1.119 GLE1 Louise Daugherty Source NHS GMS was added to GLE1.
Hereditary neuropathy v1.119 GJC2 Louise Daugherty Source NHS GMS was added to GJC2.
Hereditary neuropathy v1.119 FA2H Louise Daugherty Source NHS GMS was added to FA2H.
Hereditary neuropathy v1.119 ERBB3 Louise Daugherty Source NHS GMS was added to ERBB3.
Hereditary neuropathy v1.119 DGUOK Louise Daugherty Source NHS GMS was added to DGUOK.
Hereditary neuropathy v1.119 C19orf12 Louise Daugherty Source NHS GMS was added to C19orf12.
Hereditary neuropathy v1.119 XRCC1 Louise Daugherty Source NHS GMS was added to XRCC1.
Hereditary neuropathy v1.119 XPA Louise Daugherty Source NHS GMS was added to XPA.
Hereditary neuropathy v1.119 XK Louise Daugherty Source NHS GMS was added to XK.
Hereditary neuropathy v1.119 VPS13A Louise Daugherty Source NHS GMS was added to VPS13A.
Hereditary neuropathy v1.119 SLC25A46 Louise Daugherty Source NHS GMS was added to SLC25A46.
Hereditary neuropathy v1.119 SLC25A19 Louise Daugherty Source NHS GMS was added to SLC25A19.
Hereditary neuropathy v1.119 SCYL1 Louise Daugherty Source NHS GMS was added to SCYL1.
Hereditary neuropathy v1.119 SCARB2 Louise Daugherty Source NHS GMS was added to SCARB2.
Hereditary neuropathy v1.119 PTEN Louise Daugherty Source NHS GMS was added to PTEN.
Hereditary neuropathy v1.119 PPOX Louise Daugherty Source NHS GMS was added to PPOX.
Hereditary neuropathy v1.119 POLR3A Louise Daugherty Source NHS GMS was added to POLR3A.
Hereditary neuropathy v1.119 PNKP Louise Daugherty Source NHS GMS was added to PNKP.
Hereditary neuropathy v1.119 PMM2 Louise Daugherty Source NHS GMS was added to PMM2.
Hereditary neuropathy v1.119 PEX10 Louise Daugherty Source NHS GMS was added to PEX10.
Hereditary neuropathy v1.119 PDYN Louise Daugherty Source NHS GMS was added to PDYN.
Intellectual disability v2.856 BCORL1 Rebecca Foulger Publications for gene: BCORL1 were set to 24123876; 24896178; 26350204
Hereditary neuropathy v1.119 OPA3 Louise Daugherty Source NHS GMS was added to OPA3.
Hereditary neuropathy v1.119 OPA1 Louise Daugherty Source NHS GMS was added to OPA1.
Hereditary neuropathy v1.119 NAGA Louise Daugherty Source NHS GMS was added to NAGA.
Hereditary neuropathy v1.119 MT-TL1 Louise Daugherty Source NHS GMS was added to MT-TL1.
Hereditary neuropathy v1.119 MT-RNR1 Louise Daugherty Source NHS GMS was added to MT-RNR1.
Hereditary neuropathy v1.119 MMACHC Louise Daugherty Source NHS GMS was added to MMACHC.
Hereditary neuropathy v1.119 LYST Louise Daugherty Source NHS GMS was added to LYST.
Hereditary neuropathy v1.119 KCNA2 Louise Daugherty Source NHS GMS was added to KCNA2.
Hereditary neuropathy v1.119 IARS2 Louise Daugherty Source NHS GMS was added to IARS2.
Hereditary neuropathy v1.119 HMBS Louise Daugherty Source NHS GMS was added to HMBS.
Hereditary neuropathy v1.119 GBA2 Louise Daugherty Source NHS GMS was added to GBA2.
Hereditary neuropathy v1.119 GALC Louise Daugherty Source NHS GMS was added to GALC.
Hereditary neuropathy v1.119 FLVCR1 Louise Daugherty Source NHS GMS was added to FLVCR1.
Hereditary neuropathy v1.119 FAM126A Louise Daugherty Source NHS GMS was added to FAM126A.
Hereditary neuropathy v1.119 FAH Louise Daugherty Source NHS GMS was added to FAH.
Hereditary neuropathy v1.119 ETFDH Louise Daugherty Source NHS GMS was added to ETFDH.
Hereditary neuropathy v1.119 ERCC8 Louise Daugherty Source NHS GMS was added to ERCC8.
Hereditary neuropathy v1.119 ERCC6 Louise Daugherty Source NHS GMS was added to ERCC6.
Hereditary neuropathy v1.119 DNAJC3 Louise Daugherty Source NHS GMS was added to DNAJC3.
Hereditary neuropathy v1.119 DEGS1 Louise Daugherty Source NHS GMS was added to DEGS1.
Hereditary neuropathy v1.119 DARS2 Louise Daugherty Source NHS GMS was added to DARS2.
Hereditary neuropathy v1.119 CYP27A1 Louise Daugherty Source NHS GMS was added to CYP27A1.
Hereditary neuropathy v1.119 CPOX Louise Daugherty Source NHS GMS was added to CPOX.
Hereditary neuropathy v1.119 COA7 Louise Daugherty Source NHS GMS was added to COA7.
Hereditary neuropathy v1.119 CD59 Louise Daugherty Source NHS GMS was added to CD59.
Hereditary neuropathy v1.119 BCKDHB Louise Daugherty Source NHS GMS was added to BCKDHB.
Hereditary neuropathy v1.119 B4GALNT1 Louise Daugherty Source NHS GMS was added to B4GALNT1.
Hereditary neuropathy v1.119 ARSA Louise Daugherty Source NHS GMS was added to ARSA.
Hereditary neuropathy v1.119 APOA1 Louise Daugherty Source NHS GMS was added to APOA1.
Hereditary neuropathy v1.119 AP1S1 Louise Daugherty Source NHS GMS was added to AP1S1.
Hereditary neuropathy v1.119 AGXT Louise Daugherty Source NHS GMS was added to AGXT.
Hereditary neuropathy v1.119 AGTPBP1 Louise Daugherty Source NHS GMS was added to AGTPBP1.
Hereditary neuropathy v1.119 ABHD12 Louise Daugherty Source NHS GMS was added to ABHD12.
Hereditary neuropathy v1.119 ABCA1 Louise Daugherty Source NHS GMS was added to ABCA1.
Hereditary neuropathy v1.118 SELENOI Louise Daugherty gene: SELENOI was added
gene: SELENOI was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: SELENOI was set to
Hereditary neuropathy v1.118 SCP2 Louise Daugherty gene: SCP2 was added
gene: SCP2 was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: SCP2 was set to
Hereditary neuropathy v1.118 DSTYK Louise Daugherty gene: DSTYK was added
gene: DSTYK was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: DSTYK was set to
Hereditary neuropathy v1.118 ARL6IP1 Louise Daugherty gene: ARL6IP1 was added
gene: ARL6IP1 was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: ARL6IP1 was set to
Hereditary neuropathy v1.118 SUCLA2 Louise Daugherty gene: SUCLA2 was added
gene: SUCLA2 was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: SUCLA2 was set to
Hereditary neuropathy v1.118 PTRH2 Louise Daugherty gene: PTRH2 was added
gene: PTRH2 was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: PTRH2 was set to
Hereditary neuropathy v1.118 KLC2 Louise Daugherty gene: KLC2 was added
gene: KLC2 was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: KLC2 was set to
Intellectual disability v2.855 BCORL1 Rebecca Foulger Phenotypes for gene: BCORL1 were changed from to Intellectual disability, developmental delay and dysmorphism; Behavioral abnormality
Hereditary neuropathy v1.118 GLE1 Louise Daugherty gene: GLE1 was added
gene: GLE1 was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: GLE1 was set to
Hereditary neuropathy v1.118 GJC2 Louise Daugherty gene: GJC2 was added
gene: GJC2 was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: GJC2 was set to
Hereditary neuropathy v1.118 FA2H Louise Daugherty gene: FA2H was added
gene: FA2H was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: FA2H was set to
Hereditary neuropathy v1.118 ERBB3 Louise Daugherty gene: ERBB3 was added
gene: ERBB3 was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: ERBB3 was set to
Hereditary neuropathy v1.118 DGUOK Louise Daugherty gene: DGUOK was added
gene: DGUOK was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: DGUOK was set to
Hereditary neuropathy v1.118 C19orf12 Louise Daugherty gene: C19orf12 was added
gene: C19orf12 was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: C19orf12 was set to
Hereditary neuropathy v1.118 XRCC1 Louise Daugherty gene: XRCC1 was added
gene: XRCC1 was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: XRCC1 was set to
Hereditary neuropathy v1.118 XPA Louise Daugherty gene: XPA was added
gene: XPA was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: XPA was set to
Hereditary neuropathy v1.118 XK Louise Daugherty gene: XK was added
gene: XK was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: XK was set to
Hereditary neuropathy v1.118 VPS13A Louise Daugherty gene: VPS13A was added
gene: VPS13A was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: VPS13A was set to
Hereditary neuropathy v1.118 SLC25A46 Louise Daugherty gene: SLC25A46 was added
gene: SLC25A46 was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: SLC25A46 was set to
Hereditary neuropathy v1.118 SLC25A19 Louise Daugherty gene: SLC25A19 was added
gene: SLC25A19 was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: SLC25A19 was set to
Hereditary neuropathy v1.118 SCYL1 Louise Daugherty gene: SCYL1 was added
gene: SCYL1 was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: SCYL1 was set to
Hereditary neuropathy v1.118 SCARB2 Louise Daugherty gene: SCARB2 was added
gene: SCARB2 was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: SCARB2 was set to
Hereditary neuropathy v1.118 PTEN Louise Daugherty gene: PTEN was added
gene: PTEN was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: PTEN was set to
Hereditary neuropathy v1.118 PPOX Louise Daugherty gene: PPOX was added
gene: PPOX was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: PPOX was set to
Hereditary neuropathy v1.118 POLR3A Louise Daugherty gene: POLR3A was added
gene: POLR3A was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: POLR3A was set to
Hereditary neuropathy v1.118 PNKP Louise Daugherty gene: PNKP was added
gene: PNKP was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: PNKP was set to
Hereditary neuropathy v1.118 PMM2 Louise Daugherty gene: PMM2 was added
gene: PMM2 was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: PMM2 was set to
Hereditary neuropathy v1.118 PEX10 Louise Daugherty gene: PEX10 was added
gene: PEX10 was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: PEX10 was set to
Hereditary neuropathy v1.118 PDYN Louise Daugherty gene: PDYN was added
gene: PDYN was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: PDYN was set to
Hereditary neuropathy v1.118 OPA3 Louise Daugherty gene: OPA3 was added
gene: OPA3 was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: OPA3 was set to
Hereditary neuropathy v1.118 OPA1 Louise Daugherty gene: OPA1 was added
gene: OPA1 was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: OPA1 was set to
Hereditary neuropathy v1.118 NAGA Louise Daugherty gene: NAGA was added
gene: NAGA was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: NAGA was set to
Hereditary neuropathy v1.118 MT-TL1 Louise Daugherty gene: MT-TL1 was added
gene: MT-TL1 was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene gene: MT-TL1 was set to MITOCHONDRIAL
Hereditary neuropathy v1.118 MT-RNR1 Louise Daugherty gene: MT-RNR1 was added
gene: MT-RNR1 was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene gene: MT-RNR1 was set to MITOCHONDRIAL
Hereditary neuropathy v1.118 MMACHC Louise Daugherty gene: MMACHC was added
gene: MMACHC was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: MMACHC was set to
Hereditary neuropathy v1.118 LYST Louise Daugherty gene: LYST was added
gene: LYST was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: LYST was set to
Hereditary neuropathy v1.118 KCNA2 Louise Daugherty gene: KCNA2 was added
gene: KCNA2 was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: KCNA2 was set to
Hereditary neuropathy v1.118 IARS2 Louise Daugherty gene: IARS2 was added
gene: IARS2 was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: IARS2 was set to
Hereditary neuropathy v1.118 HMBS Louise Daugherty gene: HMBS was added
gene: HMBS was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: HMBS was set to
Hereditary neuropathy v1.118 GBA2 Louise Daugherty gene: GBA2 was added
gene: GBA2 was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: GBA2 was set to
Hereditary neuropathy v1.118 GALC Louise Daugherty gene: GALC was added
gene: GALC was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: GALC was set to
Hereditary neuropathy v1.118 FLVCR1 Louise Daugherty gene: FLVCR1 was added
gene: FLVCR1 was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: FLVCR1 was set to
Hereditary neuropathy v1.118 FAM126A Louise Daugherty gene: FAM126A was added
gene: FAM126A was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: FAM126A was set to
Hereditary neuropathy v1.118 FAH Louise Daugherty gene: FAH was added
gene: FAH was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: FAH was set to
Hereditary neuropathy v1.118 ETFDH Louise Daugherty gene: ETFDH was added
gene: ETFDH was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: ETFDH was set to
Hereditary neuropathy v1.118 ERCC8 Louise Daugherty gene: ERCC8 was added
gene: ERCC8 was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: ERCC8 was set to
Hereditary neuropathy v1.118 ERCC6 Louise Daugherty gene: ERCC6 was added
gene: ERCC6 was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: ERCC6 was set to
Hereditary neuropathy v1.118 DNAJC3 Louise Daugherty gene: DNAJC3 was added
gene: DNAJC3 was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: DNAJC3 was set to
Hereditary neuropathy v1.118 DEGS1 Louise Daugherty gene: DEGS1 was added
gene: DEGS1 was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: DEGS1 was set to
Hereditary neuropathy v1.118 DARS2 Louise Daugherty gene: DARS2 was added
gene: DARS2 was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: DARS2 was set to
Hereditary neuropathy v1.118 CYP27A1 Louise Daugherty gene: CYP27A1 was added
gene: CYP27A1 was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: CYP27A1 was set to
Hereditary neuropathy v1.118 CPOX Louise Daugherty gene: CPOX was added
gene: CPOX was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: CPOX was set to
Hereditary neuropathy v1.118 COA7 Louise Daugherty gene: COA7 was added
gene: COA7 was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: COA7 was set to
Hereditary neuropathy v1.118 CD59 Louise Daugherty gene: CD59 was added
gene: CD59 was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: CD59 was set to
Hereditary neuropathy v1.118 BCKDHB Louise Daugherty gene: BCKDHB was added
gene: BCKDHB was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: BCKDHB was set to
Hereditary neuropathy v1.118 B4GALNT1 Louise Daugherty gene: B4GALNT1 was added
gene: B4GALNT1 was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: B4GALNT1 was set to
Hereditary neuropathy v1.118 ARSA Louise Daugherty gene: ARSA was added
gene: ARSA was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: ARSA was set to
Hereditary neuropathy v1.118 APOA1 Louise Daugherty gene: APOA1 was added
gene: APOA1 was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: APOA1 was set to
Hereditary neuropathy v1.118 AP1S1 Louise Daugherty gene: AP1S1 was added
gene: AP1S1 was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: AP1S1 was set to
Hereditary neuropathy v1.118 AGXT Louise Daugherty gene: AGXT was added
gene: AGXT was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: AGXT was set to
Hereditary neuropathy v1.118 AGTPBP1 Louise Daugherty gene: AGTPBP1 was added
gene: AGTPBP1 was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: AGTPBP1 was set to
Hereditary neuropathy v1.118 ABHD12 Louise Daugherty gene: ABHD12 was added
gene: ABHD12 was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: ABHD12 was set to
Hereditary neuropathy v1.118 ABCA1 Louise Daugherty gene: ABCA1 was added
gene: ABCA1 was added to Hereditary neuropathy. Sources: London North GLH
Mode of inheritance for gene: ABCA1 was set to
Intellectual disability v2.854 BCORL1 Rebecca Foulger Mode of inheritance for gene: BCORL1 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Possible mitochondrial disorder, nuclear genes v0.200 POLRMT Ellen McDonagh Classified gene: POLRMT as Amber List (moderate evidence)
Possible mitochondrial disorder, nuclear genes v0.200 POLRMT Ellen McDonagh Added comment: Comment on list classification: After feedback from the Genomics England Clinical Team, this gene should be kept Amber as there is currently no published cases.
Possible mitochondrial disorder, nuclear genes v0.200 POLRMT Ellen McDonagh Gene: polrmt has been classified as Amber List (Moderate Evidence).
Possible mitochondrial disorder, nuclear genes v0.199 IDH3B Ellen McDonagh Classified gene: IDH3B as Amber List (moderate evidence)
Possible mitochondrial disorder, nuclear genes v0.199 IDH3B Ellen McDonagh Added comment: Comment on list classification: It was agreed on the NHSE GMS Mitochondrial Specialist Group Meeting call on 25th February 2019, that due to the organ-specific phenotype this gene should be Amber.
Possible mitochondrial disorder, nuclear genes v0.199 IDH3B Ellen McDonagh Gene: idh3b has been classified as Amber List (Moderate Evidence).
Possible mitochondrial disorder, nuclear genes v0.198 IDH3A Ellen McDonagh Classified gene: IDH3A as Amber List (moderate evidence)
Possible mitochondrial disorder, nuclear genes v0.198 IDH3A Ellen McDonagh Added comment: Comment on list classification: This gene is not associated with a disease in OMIM. One of the publications for the association given is PMID: 28412069, reporting patients with retinitis pigments accompanied by Pseudocoloboma therefore unsure if appropriate for the mitochondrial disorders panel but after feedback from the Genomics England Clinical Team should be considered for the retinal dystrophy panel. Feedback from the Genomics England clinical team was to make this Amber on the mitochondrial panels due to all but one case (reported in PMID: 28058510) are organ-specific.
Possible mitochondrial disorder, nuclear genes v0.198 IDH3A Ellen McDonagh Gene: idh3a has been classified as Amber List (Moderate Evidence).
Possible mitochondrial disorder, nuclear genes v0.197 ATP5A1 Ellen McDonagh Added comment: Comment on publications: PMID: 23599390 - the boys were reported to have inherited a heterozygous variant from their father and don’t seem to express the maternal allele, which they conclude must be due to an unknown variant affecting expression.
Possible mitochondrial disorder, nuclear genes v0.197 ATP5A1 Ellen McDonagh Publications for gene: ATP5A1 were set to 23596069; 23599390
Possible mitochondrial disorder, nuclear genes v0.196 ATP5A1 Ellen McDonagh Added comment: Comment on publications: PMID: 23599390 - the boys were reported to have inherited a heterozygous variant from their father and don’t seem to express the maternal allele, which they conclude must be due to an unknown variant affecting expression.
Possible mitochondrial disorder, nuclear genes v0.196 ATP5A1 Ellen McDonagh Publications for gene: ATP5A1 were set to 23596069; 23599390
Possible mitochondrial disorder, nuclear genes v0.195 GATB Ellen McDonagh Classified gene: GATB as Amber List (moderate evidence)
Possible mitochondrial disorder, nuclear genes v0.195 GATB Ellen McDonagh Added comment: Comment on list classification: This gene should remain Amber, as there is not enough evidence for the specific gene, as agreed for rules on gene family members.
Possible mitochondrial disorder, nuclear genes v0.195 GATB Ellen McDonagh Gene: gatb has been classified as Amber List (Moderate Evidence).
Possible mitochondrial disorder, nuclear genes v0.194 GATC Ellen McDonagh Classified gene: GATC as Amber List (moderate evidence)
Possible mitochondrial disorder, nuclear genes v0.194 GATC Ellen McDonagh Added comment: Comment on list classification: This gene should remain Amber, as there is not enough evidence for the specific gene, as agreed for rules on gene family members.
Possible mitochondrial disorder, nuclear genes v0.194 GATC Ellen McDonagh Gene: gatc has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v1.383 NDUFB10 Ellen McDonagh Publications for gene: NDUFB10 were set to
Mitochondrial disorders v1.382 NDUFA8 Ellen McDonagh Publications for gene: NDUFA8 were set to
Monogenic hearing loss v1.109 GJB2 Eleanor Williams commented on gene: GJB2
Mitochondrial disorders v1.381 SLC25A42 Ellen McDonagh Publications for gene: SLC25A42 were set to 29923093; 29327420; 26541337
Mitochondrial disorders v1.380 SLC25A42 Ellen McDonagh Added comment: Comment on phenotypes: Now in OMIM associated with the phenotype Metabolic crises, recurrent, with variable encephalomyopathic features and neurologic regression.
Mitochondrial disorders v1.380 SLC25A42 Ellen McDonagh Phenotypes for gene: SLC25A42 were changed from mitochondrial myopathy to mitochondrial myopathy; Metabolic crises, recurrent, with variable encephalomyopathic features and neurologic regression 618416
Mitochondrial disorders v1.379 NADK2 Ellen McDonagh commented on gene: NADK2
Mitochondrial disorders v1.379 NADK2 Ellen McDonagh Tag treatable tag was added to gene: NADK2.
Monogenic hearing loss v1.109 HGF Eleanor Williams commented on gene: HGF
Mitochondrial disorders v1.379 GFM2 Ellen McDonagh Publications for gene: GFM2 were set to 29075935, 22700954, 26016410
Hereditary neuropathy v1.117 WARS Louise Daugherty Mode of inheritance for gene: WARS was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary neuropathy v1.116 PMP2 Louise Daugherty Phenotypes for gene: PMP2 were changed from to Charcot-Marie-Tooth disease, demyelinating, type 1G, 618279
Hereditary neuropathy v1.115 PMP2 Louise Daugherty Mode of inheritance for gene: PMP2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary neuropathy v1.114 NEFH Louise Daugherty Phenotypes for gene: NEFH were changed from to Charcot-Marie-Tooth disease, axonal, type 2CC, 616924
Hereditary neuropathy v1.114 NEFH Louise Daugherty Phenotypes for gene: NEFH were changed from to Charcot-Marie-Tooth disease, axonal, type 2CC, 616924
Hereditary neuropathy v1.113 NEFH Louise Daugherty Mode of inheritance for gene: NEFH was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary neuropathy v1.112 MCM3AP Louise Daugherty Mode of inheritance for gene: MCM3AP was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.111 MCM3AP Louise Daugherty Phenotypes for gene: MCM3AP were changed from to Peripheral neuropathy, autosomal recessive, with or without impaired intellectual development, 618124
Hereditary neuropathy v1.110 HADHB Louise Daugherty Mode of inheritance for gene: HADHB was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.109 HADHA Louise Daugherty Phenotypes for gene: HADHA were changed from to Trifunctional protein deficiency, 609015
Hereditary neuropathy v1.108 HADHB Louise Daugherty Phenotypes for gene: HADHB were changed from to Trifunctional protein deficiency, 609015
Hereditary neuropathy v1.107 CNTNAP1 Louise Daugherty Mode of inheritance for gene: CNTNAP1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.106 CNTNAP1 Louise Daugherty Phenotypes for gene: CNTNAP1 were changed from to Hypomyelinating neuropathy, congenital, 3, 618186
Hereditary neuropathy v1.105 ZFYVE26 Louise Daugherty Phenotypes for gene: ZFYVE26 were changed from Hereditary Neuropathies; Onset second decade, spastic paraplegia, intellectual disability and cognitive decline, thin corpus callosum, mild cerebellar eye signs, axonal sensory-motor neuropathy, parkinsonism and dystonia, pseudobulbar involvement and pigmentry maculopathy to Spastic paraplegia 15, autosomal recessive, 270700; Hereditary Neuropathies; Onset second decade, spastic paraplegia, intellectual disability and cognitive decline, thin corpus callosum, mild cerebellar eye signs, axonal sensory-motor neuropathy, parkinsonism and dystonia, pseudobulbar involvement and pigmentry maculopathy
Monogenic hearing loss v1.109 SLC17A8 Eleanor Williams Publications for gene: SLC17A8 were set to PMID: 12151341; 18215623; 18674745; 19915548; 9323205
Hereditary neuropathy v1.104 ZFYVE26 Louise Daugherty Phenotypes for gene: ZFYVE26 were changed from Hereditary Neuropathies to Hereditary Neuropathies; Onset second decade, spastic paraplegia, intellectual disability and cognitive decline, thin corpus callosum, mild cerebellar eye signs, axonal sensory-motor neuropathy, parkinsonism and dystonia, pseudobulbar involvement and pigmentry maculopathy
Hereditary neuropathy v1.103 ZFYVE26 Louise Daugherty Mode of inheritance for gene: ZFYVE26 was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.102 WARS Louise Daugherty Phenotypes for gene: WARS were changed from to Neuronopathy, distal hereditary motor, type IX, 617721
Hereditary neuropathy v1.101 VCP Louise Daugherty Publications for gene: VCP were set to PMID: 26574898; 25125609; PMID: 25878907
Monogenic hearing loss v1.108 SLC17A8 Eleanor Williams commented on gene: SLC17A8
Hereditary neuropathy v1.100 TWNK Louise Daugherty Phenotypes for gene: TWNK were changed from Hereditary Neuropathies to Hereditary Neuropathies; Deafness, ovarian dysgenesis, learning difficulties, delayed motor development, cerebellar hypoplasia, peripheral axonal neuropathy
Hereditary neuropathy v1.99 TWNK Louise Daugherty Mode of inheritance for gene: TWNK was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.98 TTPA Louise Daugherty Phenotypes for gene: TTPA were changed from Hereditary Neuropathies to Hereditary Neuropathies; Early onset ataxia and sensory axonal neuropathy similar to Friedreich ataxia, head titubation, normal fat absorption unlike abetalipoproteinaemia, rarely retinitis pigmentosa
Hereditary neuropathy v1.97 TTPA Louise Daugherty Mode of inheritance for gene: TTPA was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.96 SURF1 Louise Daugherty Phenotypes for gene: SURF1 were changed from to Leigh syndrome, due to COX IV deficiency, 256000; Leigh syndrome (early onset progressive neurodegeneration of the brain stem, basal ganglia and spinal cord), neuropathy with SNCV
Hereditary neuropathy v1.95 SURF1 Louise Daugherty Mode of inheritance for gene: SURF1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.94 SPG7 Louise Daugherty Phenotypes for gene: SPG7 were changed from Hereditary Neuropathies to Hereditary Neuropathies; Spastic paraplegia, optic atrophy, ataxia and sensory-motor axonal neuropathy in some patients
Hereditary neuropathy v1.93 SPG7 Louise Daugherty Mode of inheritance for gene: SPG7 was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.92 SPAST Louise Daugherty Phenotypes for gene: SPAST were changed from Hereditary Neuropathies; Spastic paraplegia 4, autosomal dominant to Hereditary Neuropathies; Spastic paraplegia 4, autosomal dominant; Spasticity
Hereditary neuropathy v1.91 SPAST Louise Daugherty Publications for gene: SPAST were set to
Hereditary neuropathy v1.90 SOX10 Louise Daugherty Phenotypes for gene: SOX10 were changed from Waardenburg syndrome, type 4C, 613266; PCWH syndrome, 609136; Waardenburg syndrome, type 2E, with or without neurologic involvement, 611584 to Waardenburg syndrome, type 4C, 613266; PCWH syndrome, 609136; Waardenburg syndrome, type 2E, with or without neurologic involvement, 611584; Hypopigmentation of the hair and skin, sensory hearing loss, demyelinating neuropathy, dysmyelinating leukodystrophy, developmental delay, spasticity, ataxia, Hirschsprung disease
Hereditary neuropathy v1.89 PTPN11 Louise Daugherty Phenotypes for gene: PTPN11 were changed from Cardiomyopathy to Cardiomyopathy; Congenital heart defect, multiple lentigines, hypertrophic neuropathy of lumbar plexus
Hereditary neuropathy v1.88 PTPN11 Louise Daugherty Publications for gene: PTPN11 were set to
Hereditary neuropathy v1.87 PTPN11 Louise Daugherty Mode of inheritance for gene: PTPN11 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy v1.86 MTTP Louise Daugherty Publications for gene: MTTP were set to
Hereditary neuropathy v1.85 DNAJB2 Louise Daugherty Mode of inheritance for gene: DNAJB2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.84 PNPLA6 Louise Daugherty Phenotypes for gene: PNPLA6 were changed from Hereditary Neuropathies to Hereditary Neuropathies; Childhood onset of slowly progressive spastic paraplegia; progressive distal motor neuropathy beginning in early through late adolescence
Hereditary neuropathy v1.83 PNPLA6 Louise Daugherty Publications for gene: PNPLA6 were set to
Hereditary neuropathy v1.82 PNPLA6 Louise Daugherty Mode of inheritance for gene: PNPLA6 was changed from to BIALLELIC, autosomal or pseudoautosomal
Possible mitochondrial disorder, nuclear genes v0.193 GATC Sarah Leigh Classified gene: GATC as Amber List (moderate evidence)
Possible mitochondrial disorder, nuclear genes v0.193 GATC Sarah Leigh Added comment: Comment on list classification: This rating is based on the evidence that GATB, GATC & QRSL1 are functioning together in the development of this condition.
Possible mitochondrial disorder, nuclear genes v0.193 GATC Sarah Leigh Gene: gatc has been classified as Amber List (Moderate Evidence).
Possible mitochondrial disorder, nuclear genes v0.192 GATB Sarah Leigh Classified gene: GATB as Amber List (moderate evidence)
Possible mitochondrial disorder, nuclear genes v0.192 GATB Sarah Leigh Added comment: Comment on list classification: This rating is based on the evidence that GATB, GATC & QRSL1 are functioning together in the development of this condition.
Possible mitochondrial disorder, nuclear genes v0.192 GATB Sarah Leigh Gene: gatb has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.277 PKD1 Rebecca Foulger Added comment: Comment on mode of inheritance: Although not yet listed in DD-Gene2Phenotype, PKD1 is listed in OMIM with AD inheritance for Polycystic kidney disease 1, 173900. Monoallelic MOI was also listed in the original PAGE Additional gene list. However the external review and the two cited papers support both AD and AR inheritance for polycystic kidney disease (PKD). PMID:23624871 note that recessive polycystic kidney disease (ARPKD) frequently presents antenatally or in the neonatal period with severe renal involvement.
Fetal anomalies v0.277 PKD1 Rebecca Foulger Mode of inheritance for gene: PKD1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.276 PKD1 Rebecca Foulger commented on gene: PKD1: PMID:23624871 (Gilbert et al., 2013) was added as a publication by Julia Baptista. The authors describe a male fetus with renal enlargement and oligohydramnios diagnosed at 27 weeks of gestation. This presentation resembled autosomal recessive PKD (ARPKD). Genetic analysis revealed a heterozygous truncating variant (p.Ser2788fs) in PKD1 inherited from the mother, and three unreported PKD1 variants inherited from the father. Although the authors don't exclude the possibility of a pathogenic variant in an additional gene, the paternally-inherited alleles support biallelic PKD1 alleles causing the fetal kidney anomalies.
Fetal anomalies v0.276 PKD1 Rebecca Foulger commented on gene: PKD1: PMID:20558538 (Vujic et al., 2010) was added as a publication by Julia Baptista. The authors describe two pedigrees each with two patients with onset of polycystic kidney disease in-utero. Mutation analysis suggested that both families inherited, in trans, two incompletely penetrant PKD1 alleles, thus supporting autosomal recessive PKD.
Fetal anomalies v0.276 PKD1 Rebecca Foulger Added comment: Comment on mode of inheritance: Updated the MOI from monoallelic to monoallelic AND biallelic, to match the review of Julia Baptista and evidence provided in PMID:20558538 (Vujic et al., 2010) and PMID:23624871 (Gilbert et al., 2013).
Fetal anomalies v0.276 PKD1 Rebecca Foulger Mode of inheritance for gene: PKD1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.275 PKD1 Rebecca Foulger Phenotypes for gene: PKD1 were changed from Polycystic kidney disease 173900 to Polycystic kidney disease, 173900; Autosomal recessive polycystic kidney disease (ARPKD); Autosomal dominant polycystic kidney disease (ADPKD)
Fetal anomalies v0.274 PKD1 Rebecca Foulger Publications for gene: PKD1 were set to
Fetal anomalies v0.274 PKD1 Rebecca Foulger Publications for gene: PKD1 were set to
Fetal anomalies v0.273 MYRF Julia Baptista gene: MYRF was added
gene: MYRF was added to Fetal anomalies. Sources: Expert Review,Literature
Mode of inheritance for gene: MYRF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MYRF were set to PMID: 30532227; 30985895; 31069960; 30070761; 29446546 )
Phenotypes for gene: MYRF were set to congenital diaphragmatic hernia, cardiac defect, disorders of sexual development
Review for gene: MYRF was set to GREEN
Added comment: Pinz et al. 2018 reported MYRF de novo pathogenic variants in 2 unrelated male infants with cardiac-urogenital syndrome (PMID: 29446546)
Chitayat et al. (2018) reported one additional male fetus with complex congenital heart disease and severe urogenital malformations (PMID: 30070761).
Qi et al. 2018 identified 7 patients from 6 families with heterozygous MYRF variants. All of the patients had cardiac defects. Urogenital defects were present in all 4 patients who were examined (PMID: 30532227).
Rosetti et al 2019 described de novo heterozygous MYRF variants in three males. Congenital heart disease was presnet in 2/3 and diaphragmatic hernia in 2/3.
Sources: Expert Review, Literature
Possible mitochondrial disorder, nuclear genes v0.191 ATP5A1 Sarah Leigh Publications for gene: ATP5A1 were set to
Likely inborn error of metabolism v1.57 UQCRQ Sarah Leigh Phenotypes for gene: UQCRQ were changed from Mitochondrial complex III deficiency, nuclear type 4, 615159; Complex III (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS structural subunits); Mitochondrial Diseases; Isolated complex III deficiency; Mitochondrial Respiratory Chain Complex III Deficiency to Mitochondrial complex III deficiency, nuclear type 4, 615159
Undiagnosed metabolic disorders v1.109 UQCRQ Sarah Leigh Phenotypes for gene: UQCRQ were changed from Complex III (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS structural subunits); Isolated complex III deficiency; Mitochondrial complex III deficiency, nuclear type 4, 615159; Mitochondrial Respiratory Chain Complex III Deficiency; Mitochondrial Diseases to Mitochondrial complex III deficiency, nuclear type 4, 615159
Undiagnosed metabolic disorders v1.108 UQCRQ Sarah Leigh Publications for gene: UQCRQ were set to 27604308; 18439546
Likely inborn error of metabolism v1.56 UQCRQ Sarah Leigh Publications for gene: UQCRQ were set to 27604308
Undiagnosed metabolic disorders v1.107 UQCRQ Sarah Leigh Publications for gene: UQCRQ were set to 27604308
Undiagnosed metabolic disorders v1.106 UQCRQ Sarah Leigh Classified gene: UQCRQ as Amber List (moderate evidence)
Undiagnosed metabolic disorders v1.106 UQCRQ Sarah Leigh Added comment: Comment on list classification: Amber review collated by Carl Fratter (May 2019) on behalf of GMS mitochondrial specialist test group: One variant reported in a consanguineous Israeli Bedouin kindred with Mitochondrial complex III deficiency, nuclear type 4 (615159)(PMID: 18439546).
Undiagnosed metabolic disorders v1.106 UQCRQ Sarah Leigh Gene: uqcrq has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v1.55 UQCRQ Sarah Leigh Classified gene: UQCRQ as Amber List (moderate evidence)
Likely inborn error of metabolism v1.55 UQCRQ Sarah Leigh Added comment: Comment on list classification: Amber review collated by Carl Fratter (May 2019) on behalf of GMS mitochondrial specialist test group: One variant reported in a consanguineous Israeli Bedouin kindred with Mitochondrial complex III deficiency, nuclear type 4 (615159)(PMID: 18439546).
Likely inborn error of metabolism v1.55 UQCRQ Sarah Leigh Gene: uqcrq has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy v1.81 SPG11 Alexander Rossor edited their review of gene: SPG11: Changed rating: GREEN; Changed publications: 26556829; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.81 SPG11 Alexander Rossor Deleted their comment
Hereditary neuropathy v1.81 SPAST Alexander Rossor edited their review of gene: SPAST: Added comment: Peripheral neuropathy in > unrelated individuals in above case series; Changed rating: GREEN; Changed publications: 28572275; Changed phenotypes: spasticity; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy v1.81 SPAST Alexander Rossor Deleted their comment
Osteogenesis imperfecta v1.35 CREB3L1 Meena Balasubramanian reviewed gene: CREB3L1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mitochondrial disorders v1.378 UQCRQ Sarah Leigh Phenotypes for gene: UQCRQ were changed from Isolated complex III deficiency; Mitochondrial complex III deficiency, nuclear type 4, 615159; Mitochondrial Respiratory Chain Complex III Deficiency; Mitochondrial Diseases to Mitochondrial complex III deficiency, nuclear type 4, 615159
Mitochondrial disorders v1.377 UQCRQ Sarah Leigh Classified gene: UQCRQ as Amber List (moderate evidence)
Mitochondrial disorders v1.377 UQCRQ Sarah Leigh Added comment: Comment on list classification: This gene has been demoted to Amber due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter.
Mitochondrial disorders v1.377 UQCRQ Sarah Leigh Gene: uqcrq has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v1.376 UQCRQ Sarah Leigh Publications for gene: UQCRQ were set to
Amelogenesis imperfecta v1.13 RELT Eleanor Williams Phenotypes for gene: RELT were changed from amelogenesis imperfecta (hypoplastic) to amelogenesis imperfecta (hypoplastic); Amelogenesis imperfecta, type IIIC, 618386
Neurodegenerative disorders, adult onset v1.48 XPR1 Louise Daugherty Mode of inheritance for gene: XPR1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Neurodegenerative disorders, adult onset v1.47 SQSTM1 Louise Daugherty Mode of inheritance for gene: SQSTM1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Neurodegenerative disorders, adult onset v1.46 PDGFB Louise Daugherty Mode of inheritance for gene: PDGFB was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Rare multisystem ciliopathy disorders v1.84 PKD1 Julia Baptista reviewed gene: PKD1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20558538, 23624871; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Fetal anomalies v0.273 PKD1 Julia Baptista reviewed gene: PKD1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20558538, 23624871; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
DDG2P v1.45 KDM3B Rebecca Foulger commented on gene: KDM3B
DDG2P v1.45 KDM3B Rebecca Foulger gene: KDM3B was added
gene: KDM3B was added to DDG2P. Sources: Expert Review Amber,DD-Gene2Phenotype
Mode of inheritance for gene: KDM3B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KDM3B were set to 30929739
Phenotypes for gene: KDM3B were set to KDM3B-related intellectual disability, short stature and facial dysmorphism
Unexplained young onset end-stage renal disease v0.16 BNC2 Louise Daugherty Classified gene: BNC2 as Green List (high evidence)
Unexplained young onset end-stage renal disease v0.16 BNC2 Louise Daugherty Added comment: Comment on list classification: Appropriate phenotype, sufficient cases and external expert review all support gene-disease association and relevance to this panel to rate gene to Green.
Unexplained young onset end-stage renal disease v0.16 BNC2 Louise Daugherty Gene: bnc2 has been classified as Green List (High Evidence).
CAKUT v1.37 BNC2 Louise Daugherty Classified gene: BNC2 as Green List (high evidence)
CAKUT v1.37 BNC2 Louise Daugherty Added comment: Comment on list classification: Appropriate phenotype, sufficient cases and external expert review all support gene-disease association and relevance to this panel to rate gene to Green.
CAKUT v1.37 BNC2 Louise Daugherty Gene: bnc2 has been classified as Green List (High Evidence).
Unexplained young onset end-stage renal disease v0.15 BNC2 Louise Daugherty Added comment: Comment on publications: added publication to support upgrading gene to green
Unexplained young onset end-stage renal disease v0.15 BNC2 Louise Daugherty Publications for gene: BNC2 were set to
CAKUT v1.36 BNC2 Louise Daugherty Added comment: Comment on publications: added publication to support upgrading gene to green
CAKUT v1.36 BNC2 Louise Daugherty Publications for gene: BNC2 were set to
CAKUT v1.35 BNC2 Louise Daugherty Phenotypes for gene: BNC2 were changed from Posterior urethral valves; PUV to Posterior urethral valves; PUV; Congenital lower urinary-tract obstruction
Unexplained young onset end-stage renal disease v0.14 BNC2 Louise Daugherty Phenotypes for gene: BNC2 were changed from Posterior urethral valves; PUV to Posterior urethral valves; PUV; Congenital lower urinary-tract obstruction
CAKUT v1.34 BNC2 Louise Daugherty Tag watchlist was removed from gene: BNC2.
Unexplained young onset end-stage renal disease v0.13 BNC2 Louise Daugherty edited their review of gene: BNC2: Added comment: New publication PMID: 31051115 Kolvenbach CM et al., (2019) supports the rating of this gene from Amber to Green. Though exome sequencing in a family with four affected individuals with anatomical blockage of the urethra identified a rare nonsense variant (c.2557C>T [p.Arg853∗]) in BNC2, encoding basonuclin 2, tracking with LUTO over three generations. Re-sequencing BNC2 in 697 individuals with LUTO revealed three further independent missense variants in three unrelated families. In human and mouse embryogenesis, basonuclin 2 was detected in lower urinary-tract rudiments. In zebrafish embryos, bnc2 was expressed in the pronephric duct and cloaca, analogs of the mammalian lower urinary tract. Experimental knockdown of Bnc2 in zebrafish caused pronephric-outlet obstruction and cloacal dilatation, phenocopying human congenital LUTO. Collectively, these results support the conclusion that variants in BNC2 are strongly implicated in LUTO etiology as a result of anatomical blockage.; Changed rating: GREEN
CAKUT v1.34 BNC2 Louise Daugherty edited their review of gene: BNC2: Added comment: New publication PMID: 31051115 Kolvenbach CM et al., (2019) supports the rating of this gene from Amber to Green. Though exome sequencing in a family with four affected individuals with anatomical blockage of the urethra identified a rare nonsense variant (c.2557C>T [p.Arg853∗]) in BNC2, encoding basonuclin 2, tracking with LUTO over three generations. Re-sequencing BNC2 in 697 individuals with LUTO revealed three further independent missense variants in three unrelated families. In human and mouse embryogenesis, basonuclin 2 was detected in lower urinary-tract rudiments. In zebrafish embryos, bnc2 was expressed in the pronephric duct and cloaca, analogs of the mammalian lower urinary tract. Experimental knockdown of Bnc2 in zebrafish caused pronephric-outlet obstruction and cloacal dilatation, phenocopying human congenital LUTO. Collectively, these results support the conclusion that variants in BNC2 are strongly implicated in LUTO etiology as a result of anatomical blockage.; Changed rating: GREEN
Hereditary neuropathy v1.81 ZFYVE26 Alexander Rossor edited their review of gene: ZFYVE26: Changed rating: GREEN; Changed phenotypes: Onset second decade, spastic paraplegia, intellectual disability and cognitive decline, thin corpus callosum, mild cerebellar eye signs, axonal sensory-motor neuropathy, parkinsonism and dystonia, pseudobulbar involvement and pigmentry maculopathy; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.81 ZFYVE26 Alexander Rossor Deleted their comment
Hereditary neuropathy v1.81 TWNK Alexander Rossor edited their review of gene: TWNK: Changed rating: GREEN; Changed phenotypes: Deafness, ovarian dysgenesis, learning difficulties, delayed motor development, cerebellar hypoplasia, peripheral axonal neuropathy; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.81 TTPA Alexander Rossor edited their review of gene: TTPA: Changed rating: GREEN; Changed phenotypes: Early onset ataxia and sensory axonal neuropathy similar to Friedreich ataxia, head titubation, normal fat absorption unlike abetalipoproteinaemia, rarely retinitis pigmentosa; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.81 SURF1 Alexander Rossor reviewed gene: SURF1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Leigh syndrome (early onset progressive neurodegeneration of the brain stem, basal ganglia and spinal cord), neuropathy with SNCV; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.81 SPG7 Alexander Rossor Deleted their comment
Hereditary neuropathy v1.81 SPG7 Alexander Rossor edited their review of gene: SPG7: Changed rating: GREEN; Changed phenotypes: Spastic paraplegia, optic atrophy, ataxia and sensory-motor axonal neuropathy in some patients; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.81 SOX10 Alexander Rossor edited their review of gene: SOX10: Changed rating: GREEN; Changed phenotypes: Hypopigmentation of the hair and skin, sensory hearing loss, demyelinating neuropathy, dysmyelinating leukodystrophy, developmental delay, spasticity, ataxia, Hirschsprung disease.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.81 PTPN11 Alexander Rossor reviewed gene: PTPN11: Rating: GREEN; Mode of pathogenicity: None; Publications: 26952712, 26337637, 25884655; Phenotypes: Congenital heart defect, multiple lentigines, hypertrophic neuropathy of lumbar plexus; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy v1.81 PTPN11 Alexander Rossor Deleted their review
Hereditary neuropathy v1.81 PRKCG Alexander Rossor edited their review of gene: PRKCG: Added comment: Peripheral neuopathy to date only reported in a single case; Changed rating: AMBER; Changed publications: 29603387; Changed phenotypes: Usually adult onset isolated cerebellar ataxia. Missense mutation in catalytic domain of exon 11 associated with complex syndrome including cerebellar ataxia, sensory motor axonal neuropathy, parkinsonism, dystonia, myoclonus and pyramidal syndrome.; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy v1.81 PNPLA6 Alexander Rossor edited their review of gene: PNPLA6: Added comment: Complex phenotype with neuropathy (>3 families); Changed rating: GREEN; Changed publications: 24355708; Changed phenotypes: Childhood onset of slowly progressive spastic paraplegia, progressive distal motor neuropathy beginning in early through late adolescence; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.81 PNPLA6 Alexander Rossor Deleted their comment
Hereditary neuropathy v1.81 HADHB Alexander Rossor edited their review of gene: HADHB: Added comment: Trifunctional protein deficiency, causes a neuropathy as part of multisystem disease; Changed rating: GREEN
Hereditary neuropathy v1.81 HADHA Alexander Rossor edited their review of gene: HADHA: Added comment: Trifunctional protein deficiency, causes a neuropathy as part of multisystem disease; Changed rating: GREEN
Early onset or syndromic epilepsy v1.52 ALKBH8 Konstantinos Varvagiannis gene: ALKBH8 was added
gene: ALKBH8 was added to Genetic epilepsy syndromes. Sources: Literature
Mode of inheritance for gene: ALKBH8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALKBH8 were set to 31079898
Phenotypes for gene: ALKBH8 were set to Global developmental delay; Intellectual disability; Seizures
Penetrance for gene: ALKBH8 were set to Complete
Review for gene: ALKBH8 was set to AMBER
Added comment: Monies et al. (2019 - PMID: 31079898) report on 7 individuals from 2 different consanguineous Saoudi families, harboring homozygous truncating ALKBH8 pathogenic variants. The same individuals are included in another concurrent publication from the same group (Monies et al. 2019 - PMID: 31130284).

All presented with DD and ID (Fam1 : moderate in the proband, degree not commented on for his 3 sibs / Fam2 : mild in the proband, severe in all his 3 sibs). Epilepsy was reported for 6/7 individuals although the type has not been commented on (onset 9-12 months to 2 years). Variable other features were noted in few.

Affected subjects from the first family were homozygous for a stopgain variant (NM_001301010.1:c.1660C>T or p.Arg554Ter) while individuals from the second family were homozygous for a frameshift one (c.1794delC or p.Trp599Glyfs*19). The variants affected in both cases the last exon of ALKBH8 and RT-PCR confirmed that they escape NMD.

Alternative causes were ruled out, at least for the proband from the second family (chromosomal analysis, SNP-array, metabolic investigations).

Linkage analysis of both families confirmed linkage to the same autozygous interval of chr11q22.3 with a LOD score of 6.

Segregation analyses in both families, confirmed homozygosity for the truncating variants in affected members and heterozygosity in their parents (or several unaffected sibs, none of those studied was homozygous for the ref. allele).

In mouse or human cells, ALKBH8 has previously been shown to be involved in tRNA modifications of the wobble uridines of specific tRNAs (PMIDs cited: 20308323, 20583019, 21653555).

LC-MS/MS analyses of tRNA extracted from LCLs derived from affected individuals, unaffected relatives (UR) and independent controls (IC) revealed that wobble nucleotide modifications were completely absent (or dramatically decreased in the case of mcm5U) in affected individuals but readily detected in UR/IC. As specific modifications were absent, substantial amounts of precursors (eg. cm5U - the precursor of mcm5U) were detected in affected individuals but not in unaffected ones.

Absence of wobble modifications (eg. mchm5U) has equally been observed in Alkbh8 knockout mice. Alkbh8-deficient mice show similar increases in precursors. Alkbh8 KO mice are however phenotypically normal (the authors comment that eventual cognitive defects were not formally evaluated and might have been missed - PMIDs cited: 20123966, 21285950).

As a result, the studies carried out confirmed the loss-of-function effect and were in line with previous functional studies in animal models, although the pathogenesis of ID remains unclear.

The expression profile of ALKBH8 is also unclear (wide profile of expression suggested developmentally, the authors studied LCLs, other studies suggest that embryonic expression is broad but becomes progressively more restricted to specific neuronal cells).

Mutations in other genes involved in tRNA modification (eg. ADAT3, PUS3, PUS7) have been shown underlie disorders affecting the CNS, with ID as a feature.

ALKBH8 is not currently associated with any phenotype in OMIM / G2P.

As a result, this gene can be considered for inclusion in the ID/epilepsy panels as amber pending further evidence.
Sources: Literature
Intellectual disability v2.853 ALKBH8 Konstantinos Varvagiannis gene: ALKBH8 was added
gene: ALKBH8 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: ALKBH8 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ALKBH8 were set to Global developmental delay; Intellectual disability; Seizures
Penetrance for gene: ALKBH8 were set to Complete
Review for gene: ALKBH8 was set to AMBER
Added comment: Monies et al. (2019 - PMID: 31079898) report on 7 individuals from 2 different consanguineous Saoudi families, harboring homozygous truncating ALKBH8 pathogenic variants. The same individuals are included in another concurrent publication from the same group (Monies et al. 2019 - PMID: 31130284).

All presented with DD and ID (Fam1 : moderate in the proband, degree not commented on for his 3 sibs / Fam2 : mild in the proband, severe in all his 3 sibs). Epilepsy was reported for 6/7 individuals although the type has not been commented on (onset 9-12 months to 2 years). Variable other features were noted in few.

Affected subjects from the first family were homozygous for a stopgain variant (NM_001301010.1:c.1660C>T or p.Arg554Ter) while individuals from the second family were homozygous for a frameshift one (c.1794delC or p.Trp599Glyfs*19). The variants affected in both cases the last exon of ALKBH8 and RT-PCR confirmed that they escape NMD.

Alternative causes were ruled out, at least for the proband from the second family (chromosomal analysis, SNP-array, metabolic investigations).

Linkage analysis of both families confirmed linkage to the same autozygous interval of chr11q22.3 with a LOD score of 6.

Segregation analyses in both families, confirmed homozygosity for the truncating variants in affected members and heterozygosity in their parents (or several unaffected sibs, none of those studied was homozygous for the ref. allele).

In mouse or human cells, ALKBH8 has previously been shown to be involved in tRNA modifications of the wobble uridines of specific tRNAs (PMIDs cited: 20308323, 20583019, 21653555).

LC-MS/MS analyses of tRNA extracted from LCLs derived from affected individuals, unaffected relatives (UR) and independent controls (IC) revealed that wobble nucleotide modifications were completely absent (or dramatically decreased in the case of mcm5U) in affected individuals but readily detected in UR/IC. As specific modifications were absent, substantial amounts of precursors (eg. cm5U - the precursor of mcm5U) were detected in affected individuals but not in unaffected ones.

Absence of wobble modifications (eg. mchm5U) has equally been observed in Alkbh8 knockout mice. Alkbh8-deficient mice show similar increases in precursors. Alkbh8 KO mice are however phenotypically normal (the authors comment that eventual cognitive defects were not formally evaluated and might have been missed - PMIDs cited: 20123966, 21285950).

As a result, the studies carried out confirmed the loss-of-function effect and were in line with previous functional studies in animal models, although the pathogenesis of ID remains unclear.

The expression profile of ALKBH8 is also unclear (wide profile of expression suggested developmentally, the authors studied LCLs, other studies suggest that embryonic expression is broad but becomes progressively more restricted to specific neuronal cells).

Mutations in other genes involved in tRNA modification (eg. ADAT3, PUS3, PUS7) have been shown underlie disorders affecting the CNS, with ID as a feature.

ALKBH8 is not currently associated with any phenotype in OMIM / G2P.

As a result, this gene can be considered for inclusion in the ID/epilepsy panels as amber pending further evidence.
Sources: Literature
Early onset or syndromic epilepsy v1.52 AP2M1 Konstantinos Varvagiannis gene: AP2M1 was added
gene: AP2M1 was added to Genetic epilepsy syndromes. Sources: Literature
Mode of inheritance for gene: AP2M1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: AP2M1 were set to 31104773
Phenotypes for gene: AP2M1 were set to Generalized hypotonia; Global developmental delay; Intellectual disability; Seizures; Ataxia; Autistic behavior
Penetrance for gene: AP2M1 were set to Complete
Review for gene: AP2M1 was set to GREEN
Added comment: Helbig et al. (2019 - PMID: 31104773) report on 4 individuals with developmental and epileptic encephalopathy due to a recurrent de novo AP2M1 missense variant (NM_004068.3:c.508C>T or p.Arg170Trp). Seizure types included atonic, myoclonic-atonic, absence seizures (with or without eyelid myoclonia), tonic-clonic etc. Hypotonia, developmental delay (prior to the onset of seizures at 1y 3m to 4y) and intellectual disability were observed in all four. Other features included ataxia (3/4) or autism spectrum disorder (2/4).

AP2M1 encodes the μ-subunit of the adaptor protein complex 2 (AP-2). AP2M1 is highly expressed in the CNS. The AP-2 complex is involved in clathrin-mediated endocytosis at the plasma mebrane of neurons and non-neuronal cells. This mechanism is important for recycling synaptic vesicle components at mammalian central synapses. Previous evidence suggests regulation of GABA and/or glutamate receptors at the neuronal surface by AP-2 (several references provided by Helbig et al.).

The authors provide evidence for impaired (reduced) clathrin-mediated endocytosis of transferrin in AP-2μ-depleted human HeLa cells upon plasmid-based re-expression of the Arg170Trp variant compaired to re-expression of WT. A similar defect was demonstrated upon comparison of the same process when WT and Arg170Trp re-expression was studied in primary astrocytes from conditional AP-2μ knockout mice.

Expression levels, protein stability, membrane recruitment and localization of the AP-2 complex in clathrin-coated pits were similar for the Arg170Trp variant and WT. As a result, the effect of the specific variant is suggested to be mediated by alteration of the AP-2 complex function (/impaired recognition of cargo membrane proteins) rather than haploinsufficiency.

AP2M1 is highly intolerant to missense / LoF variants with z-score and pLI in ExAC of 5.82 and 0.99 respectively.

As the authors discuss, heterozygous Ap2m1 mutant mice do not have an apparent phenotype. Homozygous mutant mice die before day 3.5 postcoitus, suggesting a critical role in early embryonic development (PMID 16227583 cited)

AP2M1 is currently not associated with any phenotype in OMIM / G2P.

As a result, this gene can be considered for inclusion in the epilepsy and ID panels probably as green (4 individuals with highly similar phenotype of DEE, relevance of phenotype and/or degree of ID, functional studies, etc) rather than amber (single recurrent variant - although this is also the case for other genes rated green).
Sources: Literature
Intellectual disability v2.853 AP2M1 Konstantinos Varvagiannis gene: AP2M1 was added
gene: AP2M1 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: AP2M1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: AP2M1 were set to 31104773
Phenotypes for gene: AP2M1 were set to Generalized hypotonia; Global developmental delay; Intellectual disability; Seizures; Ataxia; Autistic behavior
Penetrance for gene: AP2M1 were set to Complete
Review for gene: AP2M1 was set to GREEN
Added comment: Helbig et al. (2019 - PMID: 31104773) report on 4 individuals with developmental and epileptic encephalopathy due to a recurrent de novo AP2M1 missense variant (NM_004068.3:c.508C>T or p.Arg170Trp). Seizure types included atonic, myoclonic-atonic, absence seizures (with or without eyelid myoclonia), tonic-clonic etc. Hypotonia, developmental delay (prior to the onset of seizures at 1y 3m to 4y) and intellectual disability were observed in all four. Other features included ataxia (3/4) or autism spectrum disorder (2/4).

AP2M1 encodes the μ-subunit of the adaptor protein complex 2 (AP-2). AP2M1 is highly expressed in the CNS. The AP-2 complex is involved in clathrin-mediated endocytosis at the plasma mebrane of neurons and non-neuronal cells. This mechanism is important for recycling synaptic vesicle components at mammalian central synapses. Previous evidence suggests regulation of GABA and/or glutamate receptors at the neuronal surface by AP-2 (several references provided by Helbig et al.).

The authors provide evidence for impaired (reduced) clathrin-mediated endocytosis of transferrin in AP-2μ-depleted human HeLa cells upon plasmid-based re-expression of the Arg170Trp variant compaired to re-expression of WT. A similar defect was demonstrated upon comparison of the same process when WT and Arg170Trp re-expression was studied in primary astrocytes from conditional AP-2μ knockout mice.

Expression levels, protein stability, membrane recruitment and localization of the AP-2 complex in clathrin-coated pits were similar for the Arg170Trp variant and WT. As a result, the effect of the specific variant is suggested to be mediated by alteration of the AP-2 complex function (/impaired recognition of cargo membrane proteins) rather than haploinsufficiency.

AP2M1 is highly intolerant to missense / LoF variants with z-score and pLI in ExAC of 5.82 and 0.99 respectively.

As the authors discuss, heterozygous Ap2m1 mutant mice do not have an apparent phenotype. Homozygous mutant mice die before day 3.5 postcoitus, suggesting a critical role in early embryonic development (PMID 16227583 cited)

AP2M1 is currently not associated with any phenotype in OMIM / G2P.

As a result, this gene can be considered for inclusion in the epilepsy and ID panels probably as green (4 individuals with highly similar phenotype of DEE, relevance of phenotype and/or degree of ID, functional studies, etc) rather than amber (single recurrent variant - although this is also the case for other genes rated green).
Sources: Literature
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.90 KCNQ1OT1 Louise Daugherty commented on gene: KCNQ1OT1: from OMIM : In 2 related individuals with Beckwith-Wiedemann syndrome, Niemitz et al. (2004) described 1 case where the deletion was maternally inherited; in the other, it was paternally inherited. In the case of maternal inheritance, the deletion caused BWS with silencing of p57(KIP2) (CDKN1C; 600856), indicating that an element important for the regulation of p57(KIP2) expression had been deleted. When inherited paternally, there was no BWS phenotype, suggesting that the LIT1 RNA itself is not necessary for normal development in humans.
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.90 HERC1 Louise Daugherty commented on gene: HERC1: Review and Amber rating from Kate Tatton-Brown April 2017: Limited evidence currently that an overgrowth gene although may be very rare contributor to overgrowth
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.90 OFD1 Louise Daugherty reviewed gene: OFD1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.90 OFD1 Louise Daugherty Publications for gene: OFD1 were set to PMID: 23036093
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.89 HIST1H1E Louise Daugherty edited their review of gene: HIST1H1E: Added comment: Review and Green rating from Kate Tatton-Brown April 2017 ; Paper in press with AJHG but we only have five cases currently. We need to ascertain more cases before we can say that the gene is an overgrowth gene. We wil be reporting variants in clinical practice soon; Changed rating: AMBER
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.89 PPP2R5D Louise Daugherty edited their review of gene: PPP2R5D: Added comment: Review and Amber rating from Kate Tatton-Brown April 2017: Few cases at the moment to be certain about the phenotype; Changed rating: AMBER
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.89 KCNQ1OT1 Louise Daugherty Classified gene: KCNQ1OT1 as Amber List (moderate evidence)
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.89 KCNQ1OT1 Louise Daugherty Gene: kcnq1ot1 has been classified as Amber List (Moderate Evidence).
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.88 KCNQ1OT1 Louise Daugherty Phenotypes for gene: KCNQ1OT1 were changed from Beckwith-Wiedemann Syndrome to Beckwith-Wiedemann Syndrome, 130650
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.87 KCNQ1OT1 Louise Daugherty Mode of inheritance for gene: KCNQ1OT1 was changed from Other - please specifiy in evaluation comments to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.86 KCNQ1OT1 Louise Daugherty Classified gene: KCNQ1OT1 as Amber List (moderate evidence)
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.86 KCNQ1OT1 Louise Daugherty Gene: kcnq1ot1 has been classified as Amber List (Moderate Evidence).
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.85 MTOR Louise Daugherty Publications for gene: MTOR were set to 28475857
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.84 AKT3 Louise Daugherty Publications for gene: AKT3 were set to 28475857
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.83 AKT3 Louise Daugherty Classified gene: AKT3 as Amber List (moderate evidence)
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.83 AKT3 Louise Daugherty Gene: akt3 has been classified as Amber List (Moderate Evidence).
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.82 AKT3 Louise Daugherty edited their review of gene: AKT3: Changed rating: AMBER
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.82 AKT3 Louise Daugherty gene: AKT3 was added
gene: AKT3 was added to Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders. Sources: Expert list
Mode of inheritance for gene: AKT3 was set to Other
Publications for gene: AKT3 were set to 28475857
Phenotypes for gene: AKT3 were set to Human overgrowth syndrome type; Overgrowth with Intellectual disability
Review for gene: AKT3 was set to GREEN
Added comment: Review and Green rating from Kate Tatton-Brown April 2017; Paper in press with AJHG. Likely activating mutations
Sources: Expert list
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.81 MTOR Louise Daugherty Classified gene: MTOR as Green List (high evidence)
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.81 MTOR Louise Daugherty Gene: mtor has been classified as Green List (High Evidence).
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.80 MTOR Louise Daugherty gene: MTOR was added
gene: MTOR was added to Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders. Sources: Expert list
Mode of inheritance for gene: MTOR was set to Other
Publications for gene: MTOR were set to 28475857
Phenotypes for gene: MTOR were set to Overgrowth with Intellectual disability; Human overgrowth syndrome type
Review for gene: MTOR was set to GREEN
Added comment: Review and Green rating from Kate Tatton-Brown April 2017; Paper in press with AJHG. Activating mutations. We wil be reporting variants in clinical practice soon
Sources: Expert list
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.79 PIK3CA Louise Daugherty Classified gene: PIK3CA as Amber List (moderate evidence)
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.79 PIK3CA Louise Daugherty Gene: pik3ca has been classified as Amber List (Moderate Evidence).
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.78 H19 Louise Daugherty Classified gene: H19 as Amber List (moderate evidence)
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.78 H19 Louise Daugherty Gene: h19 has been classified as Amber List (Moderate Evidence).
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.77 H19 Louise Daugherty Mode of inheritance for gene: H19 was changed from MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed) to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.76 PIK3CA Louise Daugherty Publications for gene: PIK3CA were set to 28475857
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.75 PIK3CA Louise Daugherty Publications for gene: PIK3CA were set to
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.74 PIK3CA Louise Daugherty Phenotypes for gene: PIK3CA were changed from Human overgrowth syndrome type to Human overgrowth syndrome type; Overgrowth with Intellectual disability
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.73 PIK3CA Louise Daugherty Mode of inheritance for gene: PIK3CA was changed from Unknown to Other
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.72 PIK3CA Louise Daugherty edited their review of gene: PIK3CA: Added comment: Review and Green rating from Kate Tatton-Brown April 2017: Activating mutations. We wil be reporting variants in clinical practice soon; Changed rating: GREEN
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.72 IGF2 Louise Daugherty Publications for gene: IGF2 were set to PMID: 17325026
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.71 KCNQ1OT1 Louise Daugherty reviewed gene: KCNQ1OT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.71 KCNQ1OT1 Louise Daugherty Publications for gene: KCNQ1OT1 were set to PMID: 12949703
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.70 IGF2 Louise Daugherty reviewed gene: IGF2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.70 H19 Louise Daugherty Mode of inheritance for gene: H19 was changed from Other - please specifiy in evaluation comments to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.69 H19 Louise Daugherty Publications for gene: H19 were set to PMID: 18836444
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.68 H19 Louise Daugherty edited their review of gene: H19: Changed mode of pathogenicity: Other
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.68 H19 Louise Daugherty reviewed gene: H19: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.68 CDKN1C Louise Daugherty Phenotypes for gene: CDKN1C were changed from Beckwith-Wiedemann syndrome; OMIM 130650; IMAGE syndrome, 614732 to Beckwith-Wiedemann syndrome, 130650; IMAGE syndrome, 614732
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.67 CDKN1C Louise Daugherty Publications for gene: CDKN1C were set to 20803657; 8841187; 20301568; 22585446; 26077438; 9341892; 26077438; 11414765; 10424811
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.66 CDKN1C Louise Daugherty Publications for gene: CDKN1C were set to PMID: 20803657; 8841187; 20301568; 22585446; 26077438; 9341892; 26077438; 11414765; 10424811
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.65 CDKN1C Louise Daugherty edited their review of gene: CDKN1C: Added comment: Review and Green rating from Kate Tatton-Brown April 2017: Note the mutations that cause Beckwith are different from the clustered CDKN1C mutations that cause IMAGe syndrome; Changed publications: 20301568, 22585446, 26077438, 9341892, 26077438, 11414765, 10424811, 9311733
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.65 PTEN Louise Daugherty Phenotypes for gene: PTEN were changed from Overgrowth with Intellectual disability Human overgrowth syndrome type to Overgrowth with Intellectual disability; Human overgrowth syndrome type
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.64 PTEN Louise Daugherty Classified gene: PTEN as Green List (high evidence)
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.64 PTEN Louise Daugherty Gene: pten has been classified as Green List (High Evidence).
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.63 PTEN Louise Daugherty Publications for gene: PTEN were set to
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.62 PTEN Louise Daugherty Mode of inheritance for gene: PTEN was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.61 PTEN Louise Daugherty Phenotypes for gene: PTEN were changed from Human overgrowth syndrome type to Overgrowth with Intellectual disability Human overgrowth syndrome type
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.60 PTEN Louise Daugherty edited their review of gene: PTEN: Added comment: Review and Green rating from Kate Tatton-Brown April 2017; Changed rating: GREEN
Intellectual disability v2.853 EED Louise Daugherty Added comment: Comment on phenotypes: extended phenotype from new publication
Intellectual disability v2.853 EED Louise Daugherty Phenotypes for gene: EED were changed from Cohen-Gibson syndrome 617561 to Cohen-Gibson syndrome, 617561; Human overgrowth syndrome type; Overgrowth with Intellectual disability
Intellectual disability v2.852 EED Louise Daugherty Publications for gene: EED were set to 25787343; 27193220; 27868325; 28229514
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.60 EED Louise Daugherty Phenotypes for gene: EED were changed from Cohen-Gibson syndrome 617561 to Cohen-Gibson syndrome, 617561; Human overgrowth syndrome type; Overgrowth with Intellectual disability
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.59 EED Louise Daugherty Publications for gene: EED were set to 25787343; 27193220; 27868325; 28229514
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.58 EED Louise Daugherty edited their review of gene: EED: Added comment: Review and Green rating from Kate Tatton-Brown April 2017. Paper in press with AJHG. Also 28229514, 25787343, 27193220, 27868325. We wil be reporting variants in clinical practice soon; Changed rating: GREEN
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.58 BRWD3 Louise Daugherty Phenotypes for gene: BRWD3 were changed from Mental retardation, X-linked 93, 300659; macrocephaly to Mental retardation, X-linked 93, 300659; macrocephaly; intellectual disability
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.57 BRWD3 Louise Daugherty Phenotypes for gene: BRWD3 were changed from Mental retardation, X-linked 93 300659 to Mental retardation, X-linked 93, 300659; macrocephaly
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.56 BRWD3 Louise Daugherty Publications for gene: BRWD3 were set to
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.55 BRWD3 Louise Daugherty edited their review of gene: BRWD3: Added comment: Review and Green rating from Kate Tatton-Brown April 2017. The paper is in press with American Journal of Human Genetics. Mutations in BRWD3 cause macrocephaly rather than overgrowth per se. We wil be reporting variants in clinical practice soon; Changed rating: GREEN
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.55 CHD8 Louise Daugherty Classified gene: CHD8 as Green List (high evidence)
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.55 CHD8 Louise Daugherty Added comment: Comment on list classification: Changed rating from Red to Green due to expert external review
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.55 CHD8 Louise Daugherty Gene: chd8 has been classified as Green List (High Evidence).
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.54 CHD8 Louise Daugherty Phenotypes for gene: CHD8 were changed from Overgrowth with Intellectual disability; Human overgrowth syndrome type to {Autism, susceptibility to, 18}, 615032; Overgrowth with Intellectual disability; Human overgrowth syndrome type
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.53 CHD8 Louise Daugherty Phenotypes for gene: CHD8 were changed from {Autism, susceptibility to, 18}, 615032; Human overgrowth syndrome type to Overgrowth with Intellectual disability; Human overgrowth syndrome type
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.52 CHD8 Louise Daugherty Publications for gene: CHD8 were set to
Intellectual disability v2.851 CHD8 Louise Daugherty Phenotypes for gene: CHD8 were changed from AUTISM to Overgrowth with Intellectual disability
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.51 CHD8 Louise Daugherty edited their review of gene: CHD8: Added comment: Review and Green rating from Kate Tatton-Brown April 2017. Paper in press with AJHG. We wil be reporting variants in clinical practice soon.; Changed rating: GREEN
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.51 CHD8 Louise Daugherty Mode of inheritance for gene: CHD8 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.50 GPC3 Louise Daugherty reviewed gene: GPC3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.50 GPC3 Louise Daugherty Publications for gene: GPC3 were set to PMID: 8589713
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.49 NFIX Louise Daugherty reviewed gene: NFIX: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.49 DNMT3A Louise Daugherty edited their review of gene: DNMT3A: Added comment: Review and Green rating from Kate Tatton-Brown April 2017: mutations can be difficult to interpret because of clonal haematopoiesis: mechanism of pathogenesis not currently understood- LOF?; Changed publications: 24614070, 26866722, 27701732, 20301652
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.49 NFIX Louise Daugherty Publications for gene: NFIX were set to PMID: 25118028
Congenital myopathy v1.149 MYBPC1 Anna Sarkozy edited their review of gene: MYBPC1: Added comment: variants in this gene were found in patients tested in Viapath/100K.

this gene causes "myopathic" forms of AMC and therefore it would be appropriate to keep these genes in a myopathy panel. perhaps it might be possible to create a subpanel for diff forms (neurogenic, myopathic, CMS?) of AMC.; Set current diagnostic: yes
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.48 NSD1 Louise Daugherty Publications for gene: NSD1 were set to PMID: 23592277
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.47 NSD1 Louise Daugherty Added comment: Comment on publications: 14997421 removed not relevant
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.47 NSD1 Louise Daugherty Publications for gene: NSD1 were set to PMID: 23592277; 14997421
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.46 NSD1 Louise Daugherty reviewed gene: NSD1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Congenital myopathy v1.149 LAMP2 Anna Sarkozy edited their review of gene: LAMP2: Added comment: note: this gene causes a vacuolar myopathy and perhaps could be also considered in the Vici syndrome and other autophagic disorders (panel 222). please discuss with the reviewers of that panel; Changed rating: AMBER; Changed publications: •12084876; Changed phenotypes: vacuolar myopathy, Danon disease; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males); Set current diagnostic: yes
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.46 EZH2 Louise Daugherty Publications for gene: EZH2 were set to 23592277; 22177091
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.45 EZH2 Louise Daugherty reviewed gene: EZH2: Rating: GREEN; Mode of pathogenicity: Other; Publications: ; Phenotypes: ; Mode of inheritance: None
Congenital myopathy v1.149 KLHL9 Anna Sarkozy reviewed gene: KLHL9: Rating: GREEN; Mode of pathogenicity: None; Publications: 20554658; Phenotypes: early onset distal myopathy; Mode of inheritance: None; Current diagnostic: yes
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.45 EZH2 Louise Daugherty Publications for gene: EZH2 were set to PMID: 23592277; 22177091
Congenital myopathy v1.149 HACD1 Anna Sarkozy edited their review of gene: HACD1: Added comment: variants were described in a single family in literature. no further confirmation to date; Changed rating: AMBER
Congenital myopathy v1.149 ECEL1 Anna Sarkozy edited their review of gene: ECEL1: Added comment: note that we have now identified at least 6 urelated families with ECEL1 gene mutations. patients present a variable degree of contractural phenotype, some with more severe Arhtrogryposis but still in keeping with a diagnosis of congenital myopathy. thus we would strongly recommend for this gene to be considered in the Cong Myopathy panel.; Changed publications: 30131190; Set current diagnostic: yes
Congenital myopathy v1.149 DOK7 Anna Sarkozy reviewed gene: DOK7: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Congenital myopathy v1.149 CNTN1 Anna Sarkozy edited their review of gene: CNTN1: Added comment: single family reported with CNTN1 variant.; Changed rating: AMBER
Hereditary spastic paraplegia, adult onset v0.153 UBAP1 Louise Daugherty Source London North GLH was added to UBAP1.
Hereditary spastic paraplegia, adult onset v0.153 ARL6IP1 Louise Daugherty Source London North GLH was added to ARL6IP1.
Congenital myopathy v1.149 CCDC78 Anna Sarkozy edited their review of gene: CCDC78: Added comment: there is so far a single family reported in literature. we only found class 3 variants in the HSS diagnostic series so far.; Changed rating: AMBER; Set current diagnostic: yes
Congenital myopathy v1.149 ACTN2 Anna Sarkozy reviewed gene: ACTN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30701273; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary spastic paraplegia, adult onset v0.152 ARL6IP1 Louise Daugherty commented on gene: ARL6IP1: Follow up review and rating after GMS Neurology Specialist Test Group Webex on 17th May 2019. Review submitted by James Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group, gene rated as AMBER
Hereditary spastic paraplegia, adult onset v0.152 UBAP1 Louise Daugherty commented on gene: UBAP1: Follow up review and rating after GMS Neurology Specialist Test Group Webex on 17th May 2019. Review submitted by James Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group, gene rated as GREEN.
Hereditary spastic paraplegia, adult onset v0.152 ARL6IP1 Louise Daugherty Classified gene: ARL6IP1 as Amber List (moderate evidence)
Hereditary spastic paraplegia, adult onset v0.152 ARL6IP1 Louise Daugherty Added comment: Comment on list classification: Gene discussed in view of onset. Gene downgraded from Green to Amber, rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.152 ARL6IP1 Louise Daugherty Gene: arl6ip1 has been classified as Amber List (Moderate Evidence).
Iron metabolism disorders - NOT common HFE mutations v0.41 ALAS2 Louise Daugherty Deleted their comment
Iron metabolism disorders - NOT common HFE mutations v0.41 SLC25A38 Louise Daugherty Deleted their comment
Iron metabolism disorders - NOT common HFE mutations v0.41 STEAP3 Louise Daugherty Classified gene: STEAP3 as Amber List (moderate evidence)
Iron metabolism disorders - NOT common HFE mutations v0.41 STEAP3 Louise Daugherty Added comment: Comment on list classification: Demoted from Green to Amber. Initial Green gene submitted by one GLH (Carl Fratter Wessex and the West Midlands GLH), subsequently after the GMS Haematology Specialist Test Group webex call 8th March 2019 Patricia Bignell (Wessex and the West Midlands GLH) reviewed gene again and suggested downgrading to Amber (webex 8.03.19 WWMGLH comments v1.doc).
Iron metabolism disorders - NOT common HFE mutations v0.41 STEAP3 Louise Daugherty Gene: steap3 has been classified as Amber List (Moderate Evidence).
Iron metabolism disorders - NOT common HFE mutations v0.40 ACVR1 Louise Daugherty Classified gene: ACVR1 as Red List (low evidence)
Iron metabolism disorders - NOT common HFE mutations v0.40 ACVR1 Louise Daugherty Added comment: Comment on list classification: Demoted from Green to Red. Initial Green gene submitted by one GLH (Carl Fratter Wessex and the West Midlands GLH), subsequently after the GMS Haematology Specialist Test Group webex call 8th March 2019 Patricia Bignell (Wessex and the West Midlands GLH) reviewed gene again and suggested downgrading to Red (webex 8.03.19 WWMGLH comments v1.doc). This is supported by the other GLHs in the Haematology Specialist Test Group
Iron metabolism disorders - NOT common HFE mutations v0.40 ACVR1 Louise Daugherty Gene: acvr1 has been classified as Red List (Low Evidence).
Cytopenia - NOT Fanconi anaemia v0.56 TUBB1 Louise Daugherty Classified gene: TUBB1 as Red List (low evidence)
Cytopenia - NOT Fanconi anaemia v0.56 TUBB1 Louise Daugherty Gene: tubb1 has been classified as Red List (Low Evidence).
Cytopenia - NOT Fanconi anaemia v0.55 TUBB1 Louise Daugherty Classified gene: TUBB1 as Amber List (moderate evidence)
Cytopenia - NOT Fanconi anaemia v0.55 TUBB1 Louise Daugherty Gene: tubb1 has been classified as Amber List (Moderate Evidence).
Cytopenia - NOT Fanconi anaemia v0.54 HOXA11 Louise Daugherty Classified gene: HOXA11 as Amber List (moderate evidence)
Cytopenia - NOT Fanconi anaemia v0.54 HOXA11 Louise Daugherty Gene: hoxa11 has been classified as Amber List (Moderate Evidence).
Fanconi anaemia or Bloom syndrome v0.21 XRCC2 Louise Daugherty Classified gene: XRCC2 as Red List (low evidence)
Fanconi anaemia or Bloom syndrome v0.21 XRCC2 Louise Daugherty Gene: xrcc2 has been classified as Red List (Low Evidence).
Bleeding and platelet disorders v0.67 UNC13D Louise Daugherty Classified gene: UNC13D as Amber List (moderate evidence)
Bleeding and platelet disorders v0.67 UNC13D Louise Daugherty Added comment: Comment on list classification: Demoted from Green to Amber. Initial Green gene submitted by one GLH (Carl Fratter Wessex and the West Midlands GLH), subsequently after the GMS Haematology Specialist Test Group webex call 8th March 2019 Patricia Bignell (Wessex and the West Midlands GLH) reviewed gene again and suggested downgrading to Amber (webex 8.03.19 WWMGLH comments v1.doc).
Bleeding and platelet disorders v0.67 UNC13D Louise Daugherty Gene: unc13d has been classified as Amber List (Moderate Evidence).
Bleeding and platelet disorders v0.66 TRPM7 Louise Daugherty Phenotypes for gene: TRPM7 were changed from macrothrombocytopenia; (NO OMIM NUMBER OR DISEASE NAME to macrothrombocytopenia
Bleeding and platelet disorders v0.65 TRPM7 Louise Daugherty Classified gene: TRPM7 as Amber List (moderate evidence)
Bleeding and platelet disorders v0.65 TRPM7 Louise Daugherty Added comment: Comment on list classification: Demoted from Green to Amber. Initial Green gene submitted by one GLH (Carl Fratter Wessex and the West Midlands GLH), subsequently after the GMS Haematology Specialist Test Group webex call 8th March 2019 Patricia Bignell (Wessex and the West Midlands GLH) reviewed gene again and suggested downgrading to Amber (webex 8.03.19 WWMGLH comments v1.doc).
Bleeding and platelet disorders v0.65 TRPM7 Louise Daugherty Gene: trpm7 has been classified as Amber List (Moderate Evidence).
Bleeding and platelet disorders v0.64 STX11 Louise Daugherty Classified gene: STX11 as Red List (low evidence)
Bleeding and platelet disorders v0.64 STX11 Louise Daugherty Added comment: Comment on list classification: Demoted from Green to Red. Initial Green gene submitted by one GLH (Carl Fratter Wessex and the West Midlands GLH), subsequently after the GMS Haematology Specialist Test Group webex call 8th March 2019 Patricia Bignell (Wessex and the West Midlands GLH) reviewed gene again and suggested downgrading to Amber (webex 8.03.19 WWMGLH comments v1.doc). Also considered Steve Keeney Red rating.
Bleeding and platelet disorders v0.64 STX11 Louise Daugherty Gene: stx11 has been classified as Red List (Low Evidence).
Bleeding and platelet disorders v0.63 SMAD4 Louise Daugherty Phenotypes for gene: SMAD4 were changed from (NO OMIM NUMBER); hereditary hemorrhagic telangiectasia syndrome to hereditary hemorrhagic telangiectasia syndrome
Bleeding and platelet disorders v0.62 SMAD4 Louise Daugherty Classified gene: SMAD4 as Red List (low evidence)
Bleeding and platelet disorders v0.62 SMAD4 Louise Daugherty Added comment: Comment on list classification: Demoted from Green to Red. Initial Green gene submitted by one GLH (Carl Fratter Wessex and the West Midlands GLH), subsequently after the GMS Haematology Specialist Test Group webex call 8th March 2019 Patricia Bignell (Wessex and the West Midlands GLH) reviewed gene again and suggested downgrading to Red (webex 8.03.19 WWMGLH comments v1.doc).
Bleeding and platelet disorders v0.62 SMAD4 Louise Daugherty Gene: smad4 has been classified as Red List (Low Evidence).
Bleeding and platelet disorders v0.61 RGS2 Louise Daugherty Classified gene: RGS2 as Amber List (moderate evidence)
Bleeding and platelet disorders v0.61 RGS2 Louise Daugherty Added comment: Comment on list classification: Demoted from Green to Amber. Initial Green gene submitted by one GLH (Carl Fratter Wessex and the West Midlands GLH), subsequently after the GMS Haematology Specialist Test Group webex call 8th March 2019 Patricia Bignell (Wessex and the West Midlands GLH) reviewed gene again and suggested downgrading to Amber (webex 8.03.19 WWMGLH comments v1.doc).
Bleeding and platelet disorders v0.61 RGS2 Louise Daugherty Gene: rgs2 has been classified as Amber List (Moderate Evidence).
Bleeding and platelet disorders v0.60 RGS2 Louise Daugherty Classified gene: RGS2 as Green List (high evidence)
Bleeding and platelet disorders v0.60 RGS2 Louise Daugherty Added comment: Comment on list classification: Demoted from Green to Amber. Initial Green gene submitted by one GLH (Carl Fratter Wessex and the West Midlands GLH), subsequently after the GMS Haematology Specialist Test Group webex call 8th March 2019 Patricia Bignell (Wessex and the West Midlands GLH) reviewed gene again and suggested downgrading to Amber (webex 8.03.19 WWMGLH comments v1.doc).
Bleeding and platelet disorders v0.60 RGS2 Louise Daugherty Gene: rgs2 has been classified as Green List (High Evidence).
Bleeding and platelet disorders v0.59 P2RX1 Louise Daugherty Classified gene: P2RX1 as Amber List (moderate evidence)
Bleeding and platelet disorders v0.59 P2RX1 Louise Daugherty Added comment: Comment on list classification: Demoted from Green to Amber. Initial Green gene submitted by one GLH (Carl Fratter Wessex and the West Midlands GLH), subsequently after the GMS Haematology Specialist Test Group webex call 8th March 2019 Patricia Bignell (Wessex and the West Midlands GLH) reviewed gene again and suggested downgrading to Amber (webex 8.03.19 WWMGLH comments v1.doc)
Bleeding and platelet disorders v0.59 P2RX1 Louise Daugherty Gene: p2rx1 has been classified as Amber List (Moderate Evidence).
Bleeding and platelet disorders v0.58 MKL1 Louise Daugherty Classified gene: MKL1 as Amber List (moderate evidence)
Bleeding and platelet disorders v0.58 MKL1 Louise Daugherty Added comment: Comment on list classification: Demoted from Green to Amber. Initial Green gene submitted by one GLH (Carl Fratter Wessex and the West Midlands GLH), subsequently after the GMS Haematology Specialist Test Group webex call 8th March 2019 Patricia Bignell (Wessex and the West Midlands GLH) reviewed gene again and suggested downgrading to Amber (webex 8.03.19 WWMGLH comments v1.doc).
Bleeding and platelet disorders v0.58 MKL1 Louise Daugherty Gene: mkl1 has been classified as Amber List (Moderate Evidence).
Bleeding and platelet disorders v0.57 GALE Louise Daugherty Classified gene: GALE as Amber List (moderate evidence)
Bleeding and platelet disorders v0.57 GALE Louise Daugherty Added comment: Comment on list classification: Demoted from Green to Amber. Initial Green gene submitted by one GLH (Carl Fratter Wessex and the West Midlands GLH), subsequently after the GMS Haematology Specialist Test Group webex call 8th March 2019 Patricia Bignell (Wessex and the West Midlands GLH) reviewed gene again and suggested downgrading to Amber (webex 8.03.19 WWMGLH comments v1.doc) comment
Bleeding and platelet disorders v0.57 GALE Louise Daugherty Gene: gale has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.273 ZFP57 Anna de Burca reviewed gene: ZFP57: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Thrombophilia with a likely monogenic cause v0.37 F3 Louise Daugherty commented on gene: F3: Follow up email correspondence with Patricia Bignell 13th March (webex 8.03.19 WWMGLH comments v1.doc), on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group, suggested rating Red
Thrombophilia with a likely monogenic cause v0.37 PROCR Louise Daugherty commented on gene: PROCR: Follow up email correspondence with Patricia Bignell 13th March (webex 8.03.19 WWMGLH comments v1.doc), on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group, suggested rating Red
Thrombophilia with a likely monogenic cause v0.37 PROZ Louise Daugherty commented on gene: PROZ: Follow up email correspondence with Patricia Bignell 13th March (webex 8.03.19 WWMGLH comments v1.doc), on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group, suggested rating Red
Thrombophilia with a likely monogenic cause v0.37 TFPI Louise Daugherty commented on gene: TFPI: Follow up email correspondence with Patricia Bignell 13th March (webex 8.03.19 WWMGLH comments v1.doc), on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group, suggested rating Red
Thrombophilia with a likely monogenic cause v0.37 PLAT Louise Daugherty commented on gene: PLAT: Follow up email correspondence with Patricia Bignell 13th March (webex 8.03.19 WWMGLH comments v1.doc), on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group, suggested rating Red
Iron metabolism disorders - NOT common HFE mutations v0.39 ABCB7 Louise Daugherty commented on gene: ABCB7: Follow up email correspondence with Patricia Bignell 13th March (webex 8.03.19 WWMGLH comments v1.doc), on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group, suggested rating Green
Iron metabolism disorders - NOT common HFE mutations v0.39 ALAS2 Louise Daugherty commented on gene: ALAS2: Follow up email correspondence with Patricia Bignell 13th March (webex 8.03.19 WWMGLH comments v1.doc), on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group, suggested rating Green
Iron metabolism disorders - NOT common HFE mutations v0.39 GLRX5 Louise Daugherty commented on gene: GLRX5: Follow up email correspondence with Patricia Bignell 13th March (webex 8.03.19 WWMGLH comments v1.doc), on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group, suggested rating Green
Iron metabolism disorders - NOT common HFE mutations v0.39 SLC25A38 Louise Daugherty commented on gene: SLC25A38: Follow up email correspondence with Patricia Bignell 13th March (webex 8.03.19 WWMGLH comments v1.doc), on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group, suggested rating Green
Iron metabolism disorders - NOT common HFE mutations v0.39 ATP7B Louise Daugherty commented on gene: ATP7B: Follow up email correspondence with Patricia Bignell 13th March (webex 8.03.19 WWMGLH comments v1.doc), on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group, suggested rating Green
Iron metabolism disorders - NOT common HFE mutations v0.39 CYBRD1 Louise Daugherty commented on gene: CYBRD1: Follow up email correspondence with Patricia Bignell 13th March (webex 8.03.19 WWMGLH comments v1.doc), on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group, suggested rating Green
Iron metabolism disorders - NOT common HFE mutations v0.39 FECH Louise Daugherty commented on gene: FECH: Follow up email correspondence with Patricia Bignell 13th March (webex 8.03.19 WWMGLH comments v1.doc), on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group, suggested rating Amber
Iron metabolism disorders - NOT common HFE mutations v0.39 GBA Louise Daugherty commented on gene: GBA: Follow up email correspondence with Patricia Bignell 13th March (webex 8.03.19 WWMGLH comments v1.doc), on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group, suggested rating Green
Iron metabolism disorders - NOT common HFE mutations v0.39 HEPH Louise Daugherty commented on gene: HEPH: Follow up email correspondence with Patricia Bignell 13th March (webex 8.03.19 WWMGLH comments v1.doc), on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group, suggested rating Amber
Iron metabolism disorders - NOT common HFE mutations v0.39 SERPINA1 Louise Daugherty commented on gene: SERPINA1: Follow up email correspondence with Patricia Bignell 13th March (webex 8.03.19 WWMGLH comments v1.doc), on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group, suggested rating Red
Iron metabolism disorders - NOT common HFE mutations v0.39 ABCB7 Louise Daugherty commented on gene: ABCB7: Follow up email correspondence with Patricia Bignell 13th March (webex 8.03.19 WWMGLH comments v1.doc), on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group, suggested rating Green
Iron metabolism disorders - NOT common HFE mutations v0.39 ALAS2 Louise Daugherty commented on gene: ALAS2: Follow up email correspondence with Patricia Bignell 13th March (webex 8.03.19 WWMGLH comments v1.doc), on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group, suggested rating Green
Iron metabolism disorders - NOT common HFE mutations v0.39 GLRX5 Louise Daugherty commented on gene: GLRX5: Follow up email correspondence with Patricia Bignell 13th March (webex 8.03.19 WWMGLH comments v1.doc), on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group, suggested rating Green
Iron metabolism disorders - NOT common HFE mutations v0.39 SLC25A38 Louise Daugherty commented on gene: SLC25A38: Follow up email correspondence with Patricia Bignell 13th March (webex 8.03.19 WWMGLH comments v1.doc), on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group, suggested rating Green
Iron metabolism disorders - NOT common HFE mutations v0.39 STEAP3 Louise Daugherty commented on gene: STEAP3: Follow up email correspondence with Patricia Bignell 13th March (webex 8.03.19 WWMGLH comments v1.doc), on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group, suggested rating Amber
Iron metabolism disorders - NOT common HFE mutations v0.39 SEC23B Louise Daugherty commented on gene: SEC23B: Follow up email correspondence with Patricia Bignell 13th March (webex 8.03.19 WWMGLH comments v1.doc), on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group, suggested rating Red
Iron metabolism disorders - NOT common HFE mutations v0.39 CDAN1 Louise Daugherty commented on gene: CDAN1: Follow up email correspondence with Patricia Bignell 13th March (webex 8.03.19 WWMGLH comments v1.doc), on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group, suggested rating Red
Iron metabolism disorders - NOT common HFE mutations v0.39 FTH1 Louise Daugherty commented on gene: FTH1: Follow up email correspondence with Patricia Bignell 13th March (webex 8.03.19 WWMGLH comments v1.doc), on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group, suggested rating Amber
Iron metabolism disorders - NOT common HFE mutations v0.39 BMP6 Louise Daugherty commented on gene: BMP6: Follow up email correspondence with Patricia Bignell 13th March (webex 8.03.19 WWMGLH comments v1.doc), on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group, suggested rating Green
Iron metabolism disorders - NOT common HFE mutations v0.39 ACVR1 Louise Daugherty commented on gene: ACVR1: Follow up email correspondence with Patricia Bignell 13th March (webex 8.03.19 WWMGLH comments v1.doc), on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group, suggested rating Red
Bleeding and platelet disorders v0.56 UNC13D Louise Daugherty commented on gene: UNC13D: Follow up email correspondence with Patricia Bignell 13th March (webex 8.03.19 WWMGLH comments v1.doc), on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group, suggested rating Amber
Bleeding and platelet disorders v0.56 TRPM7 Louise Daugherty commented on gene: TRPM7: Follow up email correspondence with Patricia Bignell 13th March (webex 8.03.19 WWMGLH comments v1.doc), on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group, suggested rating Amber
Bleeding and platelet disorders v0.56 STX11 Louise Daugherty commented on gene: STX11: Follow up email correspondence with Patricia Bignell 13th March (webex 8.03.19 WWMGLH comments v1.doc), on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group, suggested rating Amber
Bleeding and platelet disorders v0.56 SMAD4 Louise Daugherty commented on gene: SMAD4: Follow up email correspondence with Patricia Bignell 13th March (webex 8.03.19 WWMGLH comments v1.doc), on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group, suggested rating Red
Bleeding and platelet disorders v0.56 SERPINE1 Louise Daugherty commented on gene: SERPINE1: Follow up email correspondence with Patricia Bignell 13th March (webex 8.03.19 WWMGLH comments v1.doc), on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group, suggested rating Green
Bleeding and platelet disorders v0.56 RNU4ATAC Louise Daugherty commented on gene: RNU4ATAC: Follow up email correspondence with Patricia Bignell 13th March (webex 8.03.19 WWMGLH comments v1.doc), on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group, suggested rating Green
Bleeding and platelet disorders v0.56 RGS2 Louise Daugherty commented on gene: RGS2: Follow up email correspondence with Patricia Bignell 13th March (webex 8.03.19 WWMGLH comments v1.doc), on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group, suggested rating Amber
Bleeding and platelet disorders v0.56 P2RX1 Louise Daugherty commented on gene: P2RX1: Follow up email correspondence with Patricia Bignell 13th March (webex 8.03.19 WWMGLH comments v1.doc), on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group, suggested rating Amber
Bleeding and platelet disorders v0.56 MKL1 Louise Daugherty commented on gene: MKL1: Follow up email correspondence with Patricia Bignell 13th March (webex 8.03.19 WWMGLH comments v1.doc), on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group, suggested rating Amber
Bleeding and platelet disorders v0.56 LYST Louise Daugherty commented on gene: LYST: Follow up email correspondence with Patricia Bignell 13th March (webex 8.03.19 WWMGLH comments v1.doc), on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group, suggested rating Green
Bleeding and platelet disorders v0.56 GALE Louise Daugherty commented on gene: GALE: Follow up email correspondence with Patricia Bignell 13th March (webex 8.03.19 WWMGLH comments v1.doc), on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group, suggested rating Amber
Bleeding and platelet disorders v0.56 F2 Louise Daugherty commented on gene: F2: Follow up email correspondence with Patricia Bignell 13th March (webex 8.03.19 WWMGLH comments v1.doc), on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group, suggested rating Green
Thrombophilia with a likely monogenic cause v0.36 F3 Louise Daugherty Source Wessex and West Midlands GLH was added to F3.
Thrombophilia with a likely monogenic cause v0.36 PROCR Louise Daugherty Source Wessex and West Midlands GLH was added to PROCR.
Thrombophilia with a likely monogenic cause v0.36 PROZ Louise Daugherty Source Wessex and West Midlands GLH was added to PROZ.
Thrombophilia with a likely monogenic cause v0.36 TFPI Louise Daugherty Source Wessex and West Midlands GLH was added to TFPI.
Thrombophilia with a likely monogenic cause v0.36 PLAT Louise Daugherty Source Wessex and West Midlands GLH was added to PLAT.
Iron metabolism disorders - NOT common HFE mutations v0.38 SEC23B Louise Daugherty Source Wessex and West Midlands GLH was added to SEC23B.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Iron metabolism disorders - NOT common HFE mutations v0.38 CDAN1 Louise Daugherty Source Wessex and West Midlands GLH was added to CDAN1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Bleeding and platelet disorders v0.55 SERPINE1 Louise Daugherty Source Wessex and West Midlands GLH was added to SERPINE1.
Bleeding and platelet disorders v0.55 F2 Louise Daugherty Source Wessex and West Midlands GLH was added to F2.
Bleeding and platelet disorders v0.54 GALE Louise Daugherty Phenotypes for gene: GALE were changed from (NO OMIM OR DISEASE); Inherited Thrombocytopenia assiciated with mutation of UDP-Galactose-4-Epimerase (GALE) to Inherited Thrombocytopenia assiciated with mutation of UDP-Galactose-4-Epimerase (GALE)
Thrombophilia with a likely monogenic cause v0.35 F3 PATRICIA BIGNELL reviewed gene: F3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Thrombophilia with a likely monogenic cause v0.35 PROCR PATRICIA BIGNELL reviewed gene: PROCR: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Thrombophilia with a likely monogenic cause v0.35 PROZ PATRICIA BIGNELL reviewed gene: PROZ: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Thrombophilia with a likely monogenic cause v0.35 TFPI PATRICIA BIGNELL reviewed gene: TFPI: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Thrombophilia with a likely monogenic cause v0.35 PLAT PATRICIA BIGNELL reviewed gene: PLAT: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Iron metabolism disorders - NOT common HFE mutations v0.37 ABCB7 PATRICIA BIGNELL commented on gene: ABCB7: I had a discussion with Cambridge and Dr WJH Griffiths to see what he recommends for patients with iron overload; advice was to include SLC25A38, GLRX5, ALAS2 and ABCB7. We have found 8 patients with Iron overload that have a variant in the above genes.
Iron metabolism disorders - NOT common HFE mutations v0.37 ALAS2 PATRICIA BIGNELL commented on gene: ALAS2: I had a discussion with Cambridge and Dr WJH Griffiths to see what he recommends for patients with iron overload; advice was to include SLC25A38, GLRX5, ALAS2 and ABCB7. We have found 8 patients with Iron overload that have a variant in the above genes.
Iron metabolism disorders - NOT common HFE mutations v0.37 GLRX5 PATRICIA BIGNELL commented on gene: GLRX5: I had a discussion with Cambridge and Dr WJH Griffiths to see what he recommends for patients with iron overload; advice was to include SLC25A38, GLRX5, ALAS2 and ABCB7. We have found 8 patients with Iron overload that have a variant in the above genes.
Iron metabolism disorders - NOT common HFE mutations v0.37 SLC25A38 PATRICIA BIGNELL commented on gene: SLC25A38: I had a discussion with Cambridge and Dr WJH Griffiths to see what he recommends for patients with iron overload; advice was to include SLC25A38, GLRX5, ALAS2 and ABCB7. We have found 8 patients with Iron overload that have a variant in the above genes.
Iron metabolism disorders - NOT common HFE mutations v0.37 ATP7B PATRICIA BIGNELL reviewed gene: ATP7B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Iron metabolism disorders - NOT common HFE mutations v0.37 CYBRD1 PATRICIA BIGNELL reviewed gene: CYBRD1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Iron metabolism disorders - NOT common HFE mutations v0.37 FECH PATRICIA BIGNELL reviewed gene: FECH: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Iron metabolism disorders - NOT common HFE mutations v0.37 GBA PATRICIA BIGNELL reviewed gene: GBA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Iron metabolism disorders - NOT common HFE mutations v0.37 HEPH PATRICIA BIGNELL reviewed gene: HEPH: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Iron metabolism disorders - NOT common HFE mutations v0.37 SERPINA1 PATRICIA BIGNELL reviewed gene: SERPINA1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Iron metabolism disorders - NOT common HFE mutations v0.37 ABCB7 PATRICIA BIGNELL reviewed gene: ABCB7: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Iron metabolism disorders - NOT common HFE mutations v0.37 ALAS2 PATRICIA BIGNELL reviewed gene: ALAS2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Iron metabolism disorders - NOT common HFE mutations v0.37 GLRX5 PATRICIA BIGNELL reviewed gene: GLRX5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Iron metabolism disorders - NOT common HFE mutations v0.37 SLC25A38 PATRICIA BIGNELL reviewed gene: SLC25A38: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Iron metabolism disorders - NOT common HFE mutations v0.37 STEAP3 PATRICIA BIGNELL reviewed gene: STEAP3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Iron metabolism disorders - NOT common HFE mutations v0.37 SEC23B PATRICIA BIGNELL reviewed gene: SEC23B: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Iron metabolism disorders - NOT common HFE mutations v0.37 CDAN1 PATRICIA BIGNELL reviewed gene: CDAN1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Iron metabolism disorders - NOT common HFE mutations v0.37 FTH1 PATRICIA BIGNELL reviewed gene: FTH1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Iron metabolism disorders - NOT common HFE mutations v0.37 BMP6 PATRICIA BIGNELL reviewed gene: BMP6: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Iron metabolism disorders - NOT common HFE mutations v0.37 ACVR1 PATRICIA BIGNELL reviewed gene: ACVR1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Bleeding and platelet disorders v0.53 UNC13D PATRICIA BIGNELL reviewed gene: UNC13D: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Bleeding and platelet disorders v0.53 TRPM7 PATRICIA BIGNELL reviewed gene: TRPM7: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Bleeding and platelet disorders v0.53 STX11 PATRICIA BIGNELL reviewed gene: STX11: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Bleeding and platelet disorders v0.53 SMAD4 PATRICIA BIGNELL reviewed gene: SMAD4: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Bleeding and platelet disorders v0.53 SERPINE1 PATRICIA BIGNELL reviewed gene: SERPINE1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Bleeding and platelet disorders v0.53 RNU4ATAC PATRICIA BIGNELL reviewed gene: RNU4ATAC: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Bleeding and platelet disorders v0.53 RGS2 PATRICIA BIGNELL reviewed gene: RGS2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Bleeding and platelet disorders v0.53 P2RX1 PATRICIA BIGNELL reviewed gene: P2RX1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Bleeding and platelet disorders v0.53 MKL1 PATRICIA BIGNELL reviewed gene: MKL1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Bleeding and platelet disorders v0.53 LYST PATRICIA BIGNELL reviewed gene: LYST: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Bleeding and platelet disorders v0.53 GALE PATRICIA BIGNELL reviewed gene: GALE: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Bleeding and platelet disorders v0.53 F2 PATRICIA BIGNELL reviewed gene: F2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Iron metabolism disorders - NOT common HFE mutations v0.36 SERPINA1 Louise Daugherty Source Wessex and West Midlands GLH was added to SERPINA1.
Iron metabolism disorders - NOT common HFE mutations v0.36 SERPINA1 Louise Daugherty Source NHS GMS was added to SERPINA1.
Iron metabolism disorders - NOT common HFE mutations v0.36 SERPINA1 Louise Daugherty Source Yorkshire and North East GLH was added to SERPINA1.
Iron metabolism disorders - NOT common HFE mutations v0.36 SERPINA1 Louise Daugherty Source North West GLH was added to SERPINA1.
Iron metabolism disorders - NOT common HFE mutations v0.35 SERPINA1 Louise Daugherty commented on gene: SERPINA1: Changed gene listed on panel from SERPINC1 to SERPINA1, incorrect gene listed by North West GLH, Yorkshire and North East GLH and Wessex and the West Midlands GLH. The phenotype is 613490 ALPHA-1-ANTITRYPSIN DEFICIENCY; A1ATD which matches SERPINA1. Gene changed after comments from Carl Fratter and Patrica Bignell highlighting the error.
Iron metabolism disorders - NOT common HFE mutations v0.35 SERPINA1 Louise Daugherty SERPINC1 was changed to SERPINA1
Iron metabolism disorders - NOT common HFE mutations v0.35 SERPINC1 Louise Daugherty Source North West GLH was removed from SERPINC1.
Source Yorkshire and North East GLH was removed from SERPINC1.
Source NHS GMS was removed from SERPINC1.
Source Wessex and West Midlands GLH was removed from SERPINC1.
Source Expert list was added to SERPINC1.
Skeletal dysplasia v1.163 NIPBL Ellen McDonagh Publications for gene: NIPBL were set to
Intellectual disability v2.850 DOCK3 Rebecca Foulger Publications for gene: DOCK3 were set to 29130632, 28195318; 30976111
Intellectual disability v2.849 DOCK3 Rebecca Foulger Publications for gene: DOCK3 were set to 29130632, 28195318
Intellectual disability v2.848 DOCK3 Rebecca Foulger Classified gene: DOCK3 as Green List (high evidence)
Intellectual disability v2.848 DOCK3 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Red to Green based on external reviews and curation. Zornitza notes two families in her 2018 review: two siblings from Helbig et al., 2017 (PMID:28195318) plus a boy from Iwata-Otsubo et al. (2018, PMID:29130632). Konstantinos' 2019 review includes an additional 2019 paper with 3 unrelated patients harbouring biallelic DOCK3 variants and global developmental delay. Therefore there are now sufficient cases (5 unrelated) for inclusion on the ID panel as Green.
Intellectual disability v2.848 DOCK3 Rebecca Foulger Gene: dock3 has been classified as Green List (High Evidence).
Intellectual disability v2.847 DOCK3 Rebecca Foulger commented on gene: DOCK3: Helbig et al., 2017 (PMID:28195318) report 2 Ashkenazi and Yemeni Jewish siblings with severe developmental disability amongst phenotypes. WES of the siblings identified a heterozygous maternally-inherited c.382C>G (p.Gln128*) plus a paternally-inherited 458kb heterozygous deletion in 3p21.2 (which includes part of DOCK3).

PMID:30976111 (Wiltrout et al., 2019) report 3 unrelated patients with biallelic DOCK3-related global developmental delay (together with dysmorphic features in 2/3 cases).
Intellectual disability v2.847 DOCK3 Rebecca Foulger commented on gene: DOCK3
Bleeding and platelet disorders v0.52 COL3A1 Louise Daugherty edited their review of gene: COL3A1: Changed rating: AMBER
Bleeding and platelet disorders v0.52 PTPN11 Louise Daugherty edited their review of gene: PTPN11: Changed rating: RED
Bleeding and platelet disorders v0.52 COL3A1 Louise Daugherty edited their review of gene: COL3A1: Changed rating: RED
Bleeding and platelet disorders v0.52 THBD Louise Daugherty edited their review of gene: THBD: Changed rating: GREEN
Bleeding and platelet disorders v0.52 SRC Louise Daugherty edited their review of gene: SRC: Changed rating: GREEN
Bleeding and platelet disorders v0.52 RBM8A Louise Daugherty edited their review of gene: RBM8A: Changed rating: GREEN
Bleeding and platelet disorders v0.52 PLA2G4A Louise Daugherty edited their review of gene: PLA2G4A: Changed rating: GREEN
Bleeding and platelet disorders v0.52 NBEA Louise Daugherty edited their review of gene: NBEA: Changed rating: GREEN
Bleeding and platelet disorders v0.52 ITGA2 Louise Daugherty edited their review of gene: ITGA2: Changed rating: RED
Bleeding and platelet disorders v0.52 HOXA11 Louise Daugherty edited their review of gene: HOXA11: Changed rating: GREEN
Bleeding and platelet disorders v0.52 GNE Louise Daugherty edited their review of gene: GNE: Changed rating: GREEN
Bleeding and platelet disorders v0.52 ETV6 Louise Daugherty edited their review of gene: ETV6: Changed rating: GREEN
Bleeding and platelet disorders v0.52 DIAPH1 Louise Daugherty edited their review of gene: DIAPH1: Changed rating: GREEN
Bleeding and platelet disorders v0.52 CDC42 Louise Daugherty edited their review of gene: CDC42: Changed rating: GREEN
Bleeding and platelet disorders v0.52 ACTB Louise Daugherty edited their review of gene: ACTB: Changed rating: GREEN
Bleeding and platelet disorders v0.52 ABCG8 Louise Daugherty edited their review of gene: ABCG8: Changed rating: GREEN
Mitochondrial disorders v1.375 CHKB Ellen McDonagh Publications for gene: CHKB were set to
Fetal anomalies v0.273 SOX9 Rebecca Foulger edited their review of gene: SOX9: Added comment: Additional support for inclusion of gene on panel comes from Yates et al., 2017 (PMID:28425981, Whole-exome sequencing on deceased fetuses with ultrasound anomalies: expanding our knowledge of genetic disease during fetal development). Yates et al., identified a heterozygous variant in SOX9 in a case where the main ultrasound finding was Shortened and bowed long bones, talipes (Table 1).; Changed rating: AMBER; Changed phenotypes: Shortened and bowed long bones, talipes
Fetal anomalies v0.273 L1CAM Rebecca Foulger edited their review of gene: L1CAM: Added comment: Additional support for inclusion of gene on panel comes from Yates et al., 2017 (PMID:28425981, Whole-exome sequencing on deceased fetuses with ultrasound anomalies: expanding our knowledge of genetic disease during fetal development). Yates et al., identified a hemizygous variant in L1CAM in a case where the main ultrasound finding was Hydrocephalus consistent with aqueductal stenosis (Table 1).; Changed rating: AMBER; Changed phenotypes: Hydrocephalus consistent with aqueductal stenosis
Fetal anomalies v0.273 PIK3R2 Rebecca Foulger edited their review of gene: PIK3R2: Added comment: Additional support for inclusion of gene on panel comes from Yates et al., 2017 (PMID:28425981, Whole-exome sequencing on deceased fetuses with ultrasound anomalies: expanding our knowledge of genetic disease during fetal development). Yates et al., identified a heterozygous de novo likely-pathogenic variant in PIK3R2 in a case where the main ultrasound finding was Megalencephaly, neuronal migrational anomaly, congenital heart defect, heterotopias (Table 1).; Changed rating: AMBER; Changed phenotypes: Megalencephaly, neuronal migrational anomaly, congenital heart defect, heterotopias
Fetal anomalies v0.273 RIT1 Rebecca Foulger edited their review of gene: RIT1: Added comment: Additional support for inclusion of gene on panel comes from Yates et al., 2017 (PMID:28425981, Whole-exome sequencing on deceased fetuses with ultrasound anomalies: expanding our knowledge of genetic disease during fetal development). Yates et al., identified a heterozygous de novo variant in RIT1 in a case where the main ultrasound finding was Hydrops, CNS malformation, congenital heart defect (Table 1).; Changed rating: AMBER; Changed phenotypes: Hydrops, CNS malformations, congenital heart defect
Fetal anomalies v0.273 AMER1 Rebecca Foulger edited their review of gene: AMER1: Added comment: Additional support for inclusion of gene on panel comes from Yates et al., 2017 (PMID:28425981, Whole-exome sequencing on deceased fetuses with ultrasound anomalies: expanding our knowledge of genetic disease during fetal development). Yates et al., identified a hemizygous variant in AMER1 in a case where the main ultrasound finding was Macrocephaly, cleft lip and palate, congenital heart defect, bifid thumb, CNS malformation, hydrocephalus (Table 1).; Changed rating: AMBER; Changed phenotypes: Macrocephaly, cleft lip and palate, congenital heart defect, bifid thumb, CNS malformation, hydrocephalu
Fetal anomalies v0.273 FANCB Rebecca Foulger edited their review of gene: FANCB: Added comment: Additional support for inclusion of gene on panel comes from Yates et al., 2017 (PMID:28425981, Whole-exome sequencing on deceased fetuses with ultrasound anomalies: expanding our knowledge of genetic disease during fetal development). Yates et al., identified a hemizygous de novo variant in FANCB in a case where the main ultrasound finding was Ventriculomegaly, cardiac left-axis deviation, absent radii (Table 1).; Changed rating: AMBER; Changed phenotypes: Ventriculomegaly, cardiac left-axis deviation, absent radii
Fetal anomalies v0.273 CYP11A1 Rebecca Foulger edited their review of gene: CYP11A1: Added comment: Additional support for inclusion of gene on panel comes from Yates et al., 2017 (PMID:28425981, Whole-exome sequencing on deceased fetuses with ultrasound anomalies: expanding our knowledge of genetic disease during fetal development). Yates et al., identified a homozygous variant in CYP11A1 in a case where the main ultrasound finding was Hydrops, cardiomegaly (Table 1).; Changed rating: AMBER; Changed phenotypes: Hydrops, cardiomegaly
Fetal anomalies v0.273 FLNA Rebecca Foulger edited their review of gene: FLNA: Added comment: Additional support for inclusion of gene on panel comes from Yates et al., 2017 (PMID:28425981, Whole-exome sequencing on deceased fetuses with ultrasound anomalies: expanding our knowledge of genetic disease during fetal development). Yates et al., identified a hemizgyous likely-pathogenic variant in FLNA in a case where the main ultrasound finding was CNS malformations (Table 1). A heterozygous variant in PTPN11 was also reported, which the authors classify as a Possible result.; Changed rating: AMBER; Changed phenotypes: CNS malformations
Fetal anomalies v0.273 MRPS22 Rebecca Foulger edited their review of gene: MRPS22: Added comment: Support for inclusion of gene on panel comes from Yates et al., 2017 (PMID:28425981, Whole-exome sequencing on deceased fetuses with ultrasound anomalies: expanding our knowledge of genetic disease during fetal development). Yates et al., identified compound heterozygous variants in MRPS22 in a case where the main ultrasound finding was Hydrops, CNS malformations, cardiomyopathy (Table 1).; Changed phenotypes: Hydrops, CNS malformations, cardiomyopathy
Fetal anomalies v0.273 FOXP3 Rebecca Foulger edited their review of gene: FOXP3: Added comment: Additional support for inclusion of gene on panel comes from Yates et al., 2017 (PMID:28425981, Whole-exome sequencing on deceased fetuses with ultrasound anomalies: expanding our knowledge of genetic disease during fetal development). Yates et al., identified a hemizygous variant in FOXP3 in a case where the main ultrasound finding was Hydrops, contractures, echogenic kidney, placentalmegaly (Table 1). An additional variant in COL10A1 was reported that the authors classified as a possible result.; Changed rating: AMBER; Changed phenotypes: Hydrops, contractures, echogenic kidney, placentalmegaly
Fetal anomalies v0.273 PIK3CA Rebecca Foulger edited their review of gene: PIK3CA: Added comment: Additional support for inclusion of gene on panel comes from Yates et al., 2017 (PMID:28425981, Whole-exome sequencing on deceased fetuses with ultrasound anomalies: expanding our knowledge of genetic disease during fetal development). Yates et al., identified a de novo heterozygous variant in PIK3CA in a case where the main ultrasound finding was Brain malformations (Table 1). An inherited MYH3 variant was also detected in this case but was reclassified as likely benign based on allele frequency data.; Changed rating: AMBER; Changed phenotypes: Brain malformations
Fetal anomalies v0.273 PTPN11 Rebecca Foulger edited their review of gene: PTPN11: Added comment: Additional support for inclusion of gene on panel comes from Yates et al., 2017 (PMID:28425981, Whole-exome sequencing on deceased fetuses with ultrasound anomalies: expanding our knowledge of genetic disease during fetal development). Yates et al., identified a heterozygous de novo variant in PTPN11 in a case where the main ultrasound finding was Syndactyly, polydactyly (Table 1). An additional likely-pathogenic variant was identified in WDR35.; Changed rating: AMBER; Changed phenotypes: Syndactyly, polydactyly
Fetal anomalies v0.273 FGFR2 Rebecca Foulger edited their review of gene: FGFR2: Added comment: Additional support for inclusion of gene on panel comes from Yates et al., 2017 (PMID:28425981, Whole-exome sequencing on deceased fetuses with ultrasound anomalies: expanding our knowledge of genetic disease during fetal development). Yates et al., identified a heterozygous de novo variant in FGFR2 in a case where the main ultrasound finding was Fontal bossing, talipes, syndactyly, abducted thumbs (Table 1).; Changed rating: AMBER; Changed phenotypes: Fontal bossing, talipes, syndactyly, abducted thumbs
Fetal anomalies v0.273 RIPK4 Rebecca Foulger edited their review of gene: RIPK4: Added comment: Additional support for inclusion of gene on panel comes from Yates et al., 2017 (PMID:28425981, Whole-exome sequencing on deceased fetuses with ultrasound anomalies: expanding our knowledge of genetic disease during fetal development). Yates et al., identified a heterozygous likely pathogenic variant in RIPK4 (plus a heterozygous VUS) in a case where the main ultrasound finding was Hydrops, diaphragmatic hernia, gracile ribs, contractures (Table 1). Additional VUS variants were reported in RSAD1 and PPAP2C.; Changed rating: AMBER; Changed phenotypes: Hydrops, diaphragmatic hernia, gracile ribs, contractures
Fetal anomalies v0.273 HRAS Rebecca Foulger edited their review of gene: HRAS: Added comment: Additional support for inclusion of gene on panel comes from Yates et al., 2017 (PMID:28425981, Whole-exome sequencing on deceased fetuses with ultrasound anomalies: expanding our knowledge of genetic disease during fetal development). Yates et al., identified a heterozygous variant in HRAS in a case where the main ultrasound finding was Hydrops (Table 1).; Changed rating: AMBER; Changed phenotypes: Hydrops
Fetal anomalies v0.273 BBS4 Rebecca Foulger edited their review of gene: BBS4: Added comment: Additional support for inclusion of gene on panel comes from Yates et al., 2017 (PMID:28425981, Whole-exome sequencing on deceased fetuses with ultrasound anomalies: expanding our knowledge of genetic disease during fetal development). Yates et al., identified a pathogenic variant in BBS4 in a case where the main ultrasound finding was Bilateral enlarged cystic kidneys (Table 1). VUS variants in ANKS6 and PKD1 were also reported.; Changed rating: AMBER; Changed phenotypes: Bilateral enlarged cystic kidneys
Fetal anomalies v0.273 PIEZO1 Rebecca Foulger edited their review of gene: PIEZO1: Added comment: Additional support for inclusion of gene on panel comes from Yates et al., 2017 (PMID:28425981, Whole-exome sequencing on deceased fetuses with ultrasound anomalies: expanding our knowledge of genetic disease during fetal development). Yates et al., identified a case with two homozygous variants in PIEZO1 (one pathogenic, one VUS), where the main ultrasound finding was Hydrops (Table 1).; Changed rating: AMBER; Changed phenotypes: Hydrops
Intellectual disability v2.847 DYNC1I2 Konstantinos Varvagiannis gene: DYNC1I2 was added
gene: DYNC1I2 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: DYNC1I2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DYNC1I2 were set to 31079899
Phenotypes for gene: DYNC1I2 were set to Microcephaly; Intellectual disability; Abnormality of nervous system morphology; Abnormality of head or neck
Penetrance for gene: DYNC1I2 were set to Complete
Review for gene: DYNC1I2 was set to AMBER
Added comment: Ansar et al. (2019 - PMID: 31079899) report on five individuals from 3 families, with biallelic likely pathogenic DYNC1I2 variants.

The phenotype consisted of microcephaly, intellectual disability, cerebral malformations and suggestive facial features. 2/5 individuals, from different families presented seizures.

Affected individuals from a consanguineous Pakistani family were homozygous for a splicing variant (c.607+1G>A - RNA was unavailable for further studies). One individual from a futher family was compound heterozygous for a missense variant (c.740A>G or p.Tyr247Cys) and a 374 kb deletion encompassing DYNC1I2 as well as 3 other genes (DCAF17, CYBRD1, SLC25A12). Another individual was found to harbor c.740A>G (p.Tyr247Cys) in trans with c.868C>T (p.Gln290*). [NM_001378.2 used as reference].

DYNC1I2 encodes Dynein Cytoplasmic 1 intermediate chain 2, a component of the cytoplasmic dynein 1 complex. This complex is involved in retrograde cargo transport within the cytoplasmic microtubule network. Emerging evidence suggests a critical role of this complex in neurodevelopment and homeostasis (PMIDs cited by the authors: 25374356, 28395088). Mutations in other genes encoding components of the complex (principally DYNC1H1) give rise to neurological disorders, some of which with ID as a principal feature (eg. Mental retardation, autosomal dominant 13 - MIM 614563).

In zebrafish, DYNC1I2 has 2 orthologs - dync1i2a and dync1i2b. The former is suggested to be the functionally relevant DYNC1I2 ortholog as CRISPR-Cas9 dync1i2a disruption and/or suppression with morpholinos resulted in altered craniofacial patterning and reduction in head size (similar to the microcephaly phenotype reported in affected individuals).

In vivo complementation studies suggested a loss of function effect for the p.Tyr247Cys variant, similar to the p.Gln290* one.

Evidence is provided for a role of increased apoptosis, probably secondary to altered cell cycle progression (prolonged mitosis due to abnormal spindle morphology), to explain the reduced head size/microcephaly phenotype.

There is no associated phenotype in OMIM/G2P.

As a result, DYNC1I2 could be considered for inclusion in the ID panel probably as amber (ID reported for 5 individuals from 3 families, severity of ID not specified for all, eg. fam. 2 for whom the deletion was also spanning other genes which might contribute to the phenotype).
Sources: Literature
Intellectual disability v2.847 DOCK3 Rebecca Foulger Phenotypes for gene: DOCK3 were changed from to Neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia, 618292
Mitochondrial disorders v1.374 UQCRB Sarah Leigh Phenotypes for gene: UQCRB were changed from Isolated complex III deficiency; Mitochondrial complex III deficiency, nuclear type 3, 615158; Mitochondrial Diseases to Mitochondrial complex III deficiency, nuclear type 3, 615158
Mitochondrial disorders v1.373 UQCRB Sarah Leigh Publications for gene: UQCRB were set to 12709789; 25446085; 23454382
Mitochondrial disorders v1.372 UQCRB Sarah Leigh Added comment: Comment on publications: PMID: 12709789 (case report);PMID: 25446085 (functional study);PMID: 23454382 (functional study)
Mitochondrial disorders v1.372 UQCRB Sarah Leigh Publications for gene: UQCRB were set to PMID: 12709789 (case report); PMID: 25446085 (functional study); PMID: 23454382 (functional study)
Mitochondrial disorders v1.371 UQCRB Sarah Leigh Classified gene: UQCRB as Green List (high evidence)
Mitochondrial disorders v1.371 UQCRB Sarah Leigh Added comment: Comment on list classification: This gene was added as Green due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter (May 2019) on behalf of GMS mitochondrial specialist test group: 2 unrelated cases with functional studies.
From panels: Possible mitochondrial disorder - nuclear genes (Version 0.187) and Mitochondrial disorder with complex III deficiency (Version 0.25).
Mitochondrial disorders v1.371 UQCRB Sarah Leigh Gene: uqcrb has been classified as Green List (High Evidence).
Mitochondrial disorders v1.370 UQCC2 Sarah Leigh Phenotypes for gene: UQCC2 were changed from Isolated complex III deficiency; Mitochondrial complex III deficiency, nuclear type 7, MIM#615824 to Mitochondrial complex III deficiency, nuclear type 7, 615824
Mitochondrial disorders v1.369 UQCC2 Sarah Leigh Classified gene: UQCC2 as Green List (high evidence)
Mitochondrial disorders v1.369 UQCC2 Sarah Leigh Added comment: Comment on list classification: This gene was added as Green due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter (May 2019) on behalf of GMS mitochondrial specialist test group: 2 unrelated cases with functional studies.
From panels: Possible mitochondrial disorder - nuclear genes (Version 0.187) and Mitochondrial disorder with complex III deficiency (Version 0.25).
Mitochondrial disorders v1.369 UQCC2 Sarah Leigh Gene: uqcc2 has been classified as Green List (High Evidence).
Mitochondrial disorders v1.368 TRMT10C Sarah Leigh Phenotypes for gene: TRMT10C were changed from Multiple respiratory chain complex deficiencies (disorders of protein synthesis) to Combined oxidative phosphorylation deficiency 30, 616974
Mitochondrial disorders v1.367 TRMT10C Sarah Leigh Mode of inheritance for gene: TRMT10C was changed from to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v1.366 TRMT10C Sarah Leigh Classified gene: TRMT10C as Green List (high evidence)
Mitochondrial disorders v1.366 TRMT10C Sarah Leigh Added comment: Comment on list classification: This gene was added as Green due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter (May 2019) on behalf of GMS mitochondrial specialist test group: 2 unrelated families with functional studies.
From panel: Possible mitochondrial disorder - nuclear genes (Version 0.187).
Mitochondrial disorders v1.366 TRMT10C Sarah Leigh Gene: trmt10c has been classified as Green List (High Evidence).
Mitochondrial disorders v1.365 TRMT10C Sarah Leigh Publications for gene: TRMT10C were set to
Mitochondrial disorders v1.364 TOP3A Sarah Leigh Classified gene: TOP3A as Green List (high evidence)
Mitochondrial disorders v1.364 TOP3A Sarah Leigh Added comment: Comment on list classification: This gene was added as Green due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter (May 2019) on behalf of GMS mitochondrial specialist test group: One case reported with functional studies; Newcastle team aware of another unrelated case.
From panel: Possible mitochondrial disorder - nuclear genes (Version 0.187).
Mitochondrial disorders v1.364 TOP3A Sarah Leigh Gene: top3a has been classified as Green List (High Evidence).
Mitochondrial disorders v1.363 SLC25A32 Sarah Leigh Phenotypes for gene: SLC25A32 were changed from to ?Exercise intolerance, riboflavin-responsive 616839
Mitochondrial disorders v1.362 SLC25A32 Sarah Leigh Mode of inheritance for gene: SLC25A32 was changed from to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v1.361 SLC25A32 Sarah Leigh Classified gene: SLC25A32 as Green List (high evidence)
Mitochondrial disorders v1.361 SLC25A32 Sarah Leigh Added comment: Comment on list classification: This gene was added as Green due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter (May 2019) on behalf of GMS mitochondrial specialist test group: 2 unrelated cases with functional studies.
From panel: Possible mitochondrial disorder - nuclear genes (Version 0.187).
Mitochondrial disorders v1.361 SLC25A32 Sarah Leigh Gene: slc25a32 has been classified as Green List (High Evidence).
Mitochondrial disorders v1.360 SLC25A32 Sarah Leigh commented on gene: SLC25A32
Mitochondrial disorders v1.360 SLC25A32 Sarah Leigh Tag treatable tag was added to gene: SLC25A32.
Mitochondrial disorders v1.360 SLC25A32 Sarah Leigh Publications for gene: SLC25A32 were set to
Mitochondrial disorders v1.359 SFXN4 Sarah Leigh Classified gene: SFXN4 as Green List (high evidence)
Mitochondrial disorders v1.359 SFXN4 Sarah Leigh Added comment: Comment on list classification: This gene was added as Green due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter (May 2019) on behalf of GMS mitochondrial specialist test group: 2 unrelated cases with functional studies.
From panel: Possible mitochondrial disorder - nuclear genes (Version 0.187).
Mitochondrial disorders v1.359 SFXN4 Sarah Leigh Gene: sfxn4 has been classified as Green List (High Evidence).
Mitochondrial disorders v1.358 SDHD Sarah Leigh Phenotypes for gene: SDHD were changed from Mitochondrial Diseases; Isolated complex II deficiency to Mitochondrial respiratory chain complex II deficiency 252011
Mitochondrial disorders v1.357 SDHD Sarah Leigh Publications for gene: SDHD were set to
Mitochondrial disorders v1.356 SDHD Sarah Leigh Classified gene: SDHD as Green List (high evidence)
Mitochondrial disorders v1.356 SDHD Sarah Leigh Added comment: Comment on list classification: This gene was added as Green due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter (May 2019) on behalf of GMS mitochondrial specialist test group: 2 unrelated cases with functional studies.
From panels: Possible mitochondrial disorder - nuclear genes (Version 0.187) and Mitochondrial disorder with complex II deficiency (Version 0.16).
Mitochondrial disorders v1.356 SDHD Sarah Leigh Gene: sdhd has been classified as Green List (High Evidence).
Mitochondrial disorders v1.355 SDHAF1 Sarah Leigh Publications for gene: SDHAF1 were set to
Mitochondrial disorders v1.354 SDHAF1 Sarah Leigh Phenotypes for gene: SDHAF1 were changed from Isolated complex II deficiency; Mitochondrial complex II deficiency, 252011; Mitochondrial Diseases; Mitochondrial Respiratory Chain Complex II Deficiency to Mitochondrial complex II deficiency, 252011
Mitochondrial disorders v1.353 SDHAF1 Sarah Leigh Added comment: Comment on phenotypes: Mitochondrial complex II deficiency, 252011
Mitochondrial disorders v1.353 SDHAF1 Sarah Leigh Phenotypes for gene: SDHAF1 were changed from Isolated complex II deficiency; Mitochondrial complex II deficiency, 252011; Mitochondrial Diseases; Mitochondrial Respiratory Chain Complex II Deficiency to Isolated complex II deficiency; Mitochondrial complex II deficiency, 252011; Mitochondrial Diseases; Mitochondrial Respiratory Chain Complex II Deficiency
Mitochondrial disorders v1.352 SDHAF1 Sarah Leigh Classified gene: SDHAF1 as Green List (high evidence)
Mitochondrial disorders v1.352 SDHAF1 Sarah Leigh Added comment: Comment on list classification: This gene was added as Green due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter (May 2019) on behalf of GMS mitochondrial specialist test group: Multiple unrelated cases with functional studies.
From panels: Possible mitochondrial disorder - nuclear genes (Version 0.187) and Mitochondrial disorder with complex II deficiency (Version 0.16).
Mitochondrial disorders v1.352 SDHAF1 Sarah Leigh Gene: sdhaf1 has been classified as Green List (High Evidence).
Fetal anomalies v0.272 SOX9 Rebecca Foulger Publications for gene: SOX9 were set to
Fetal anomalies v0.271 L1CAM Rebecca Foulger Publications for gene: L1CAM were set to
Fetal anomalies v0.270 PIK3R2 Rebecca Foulger Publications for gene: PIK3R2 were set to
Fetal anomalies v0.269 RIT1 Rebecca Foulger Publications for gene: RIT1 were set to
Fetal anomalies v0.268 AMER1 Rebecca Foulger Publications for gene: AMER1 were set to 8425981
Fetal anomalies v0.267 AMER1 Rebecca Foulger Publications for gene: AMER1 were set to
Fetal anomalies v0.266 FANCB Rebecca Foulger Publications for gene: FANCB were set to
Fetal anomalies v0.265 CYP11A1 Rebecca Foulger Publications for gene: CYP11A1 were set to
Fetal anomalies v0.264 FLNA Rebecca Foulger Publications for gene: FLNA were set to
Fetal anomalies v0.263 MRPS22 Rebecca Foulger Publications for gene: MRPS22 were set to
Fetal anomalies v0.262 FOXP3 Rebecca Foulger Publications for gene: FOXP3 were set to
Fetal anomalies v0.261 PIK3CA Rebecca Foulger Publications for gene: PIK3CA were set to
Fetal anomalies v0.260 PTPN11 Rebecca Foulger Publications for gene: PTPN11 were set to
Mitochondrial disorders v1.351 PNPLA8 Sarah Leigh Publications for gene: PNPLA8 were set to 29681094; 25512002
Fetal anomalies v0.259 FGFR2 Rebecca Foulger Publications for gene: FGFR2 were set to
Mitochondrial disorders v1.350 PNPLA8 Sarah Leigh Classified gene: PNPLA8 as Green List (high evidence)
Mitochondrial disorders v1.350 PNPLA8 Sarah Leigh Added comment: Comment on list classification: This gene was added as Green due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter (May 2019) on behalf of GMS mitochondrial specialist test group: 3 or 4 unrelated cases and functional studies.
From panel: Possible mitochondrial disorder - nuclear genes (Version 0.187).
Mitochondrial disorders v1.350 PNPLA8 Sarah Leigh Gene: pnpla8 has been classified as Green List (High Evidence).
Fetal anomalies v0.258 RIPK4 Rebecca Foulger Publications for gene: RIPK4 were set to
Fetal anomalies v0.257 HRAS Rebecca Foulger Publications for gene: HRAS were set to
Mitochondrial disorders v1.349 PMPCB Sarah Leigh Phenotypes for gene: PMPCB were changed from to Multiple mitochondrial dysfunctions syndrome 6, 617954
Fetal anomalies v0.256 BBS4 Rebecca Foulger Publications for gene: BBS4 were set to
Mitochondrial disorders v1.348 PMPCB Sarah Leigh Publications for gene: PMPCB were set to
Fetal anomalies v0.255 PIEZO1 Rebecca Foulger Publications for gene: PIEZO1 were set to 26333996; 23695678
Mitochondrial disorders v1.347 PMPCB Sarah Leigh Mode of inheritance for gene: PMPCB was changed from to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v1.346 PMPCB Sarah Leigh Classified gene: PMPCB as Green List (high evidence)
Mitochondrial disorders v1.346 PMPCB Sarah Leigh Added comment: Comment on list classification: This gene was added as Green due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter (May 2019) on behalf of GMS mitochondrial specialist test group: 4 unrelated families/patients.
From panel: Possible mitochondrial disorder - nuclear genes (Version 0.187).
Mitochondrial disorders v1.346 PMPCB Sarah Leigh Gene: pmpcb has been classified as Green List (High Evidence).
Fetal anomalies v0.254 GJB2 Rebecca Foulger Publications for gene: GJB2 were set to
Mitochondrial disorders v1.345 NDUFB8 Sarah Leigh Phenotypes for gene: NDUFB8 were changed from Isolated complex I deficiency; No OMIM phenotype to Mitochondrial complex I deficiency, nuclear type 32, 618252
Mitochondrial disorders v1.344 NDUFB8 Sarah Leigh Mode of inheritance for gene: NDUFB8 was changed from to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v1.343 NDUFB8 Sarah Leigh Publications for gene: NDUFB8 were set to
Mitochondrial disorders v1.342 NDUFB8 Sarah Leigh Classified gene: NDUFB8 as Green List (high evidence)
Mitochondrial disorders v1.342 NDUFB8 Sarah Leigh Added comment: Comment on list classification: This gene was added as Green due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter (May 2019) on behalf of GMS mitochondrial specialist test group: 2 unrelated cases with functional studies.
From panels: Possible mitochondrial disorder - nuclear genes (Version 0.187) and Mitochondrial disorder with complex I deficiency (Version 0.65).
Mitochondrial disorders v1.342 NDUFB8 Sarah Leigh Gene: ndufb8 has been classified as Green List (High Evidence).
Fetal anomalies v0.253 BRAT1 Rebecca Foulger Publications for gene: BRAT1 were set to
Mitochondrial disorders v1.341 NDUFAF8 Sarah Leigh Classified gene: NDUFAF8 as Green List (high evidence)
Mitochondrial disorders v1.341 NDUFAF8 Sarah Leigh Added comment: Comment on list classification: This gene was added as Green due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter (May 2019) on behalf of GMS mitochondrial specialist test group: Newcastle team are aware of 3 unrelated cases and functional studies.
From panels: Possible mitochondrial disorder - nuclear genes (Version 0.187) and Mitochondrial disorder with complex I deficiency (Version 0.65).
Mitochondrial disorders v1.341 NDUFAF8 Sarah Leigh Gene: ndufaf8 has been classified as Green List (High Evidence).
Mitochondrial disorders v1.340 NDUFAF8 Sarah Leigh Added comment: Comment on phenotypes: No OMIM phenotype (23/05/2019).
Mitochondrial disorders v1.340 NDUFAF8 Sarah Leigh Phenotypes for gene: NDUFAF8 were changed from to No OMIM phenotype
Mitochondrial disorders v1.339 NDUFAF8 Sarah Leigh Publications for gene: NDUFAF8 were set to
Mitochondrial disorders v1.338 NDUFAF8 Sarah Leigh Mode of inheritance for gene: NDUFAF8 was changed from to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v1.337 NDUFA9 Sarah Leigh Classified gene: NDUFA9 as Green List (high evidence)
Mitochondrial disorders v1.337 NDUFA9 Sarah Leigh Added comment: Comment on list classification: This gene was added as Green due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter (May 2019) on behalf of GMS mitochondrial specialist test group: 2 unrelated families with functional studies.
From panels: Possible mitochondrial disorder - nuclear genes (Version 0.187) and Mitochondrial disorder with complex I deficiency (Version 0.65).
Mitochondrial disorders v1.337 NDUFA9 Sarah Leigh Gene: ndufa9 has been classified as Green List (High Evidence).
Mitochondrial disorders v1.336 NDUFA9 Sarah Leigh Added comment: Comment on phenotypes: Leigh syndrome due to mitochondrial complex I deficiency, 256000 was previously listed for this gene, however, NDUFA9 is not associated with this phenotyped in OMIM.
Mitochondrial disorders v1.336 NDUFA9 Sarah Leigh Phenotypes for gene: NDUFA9 were changed from Isolated complex I deficiency; Leigh syndrome due to mitochondrial complex I deficiency, 256000 to Mitochondrial complex I deficiency, nuclear type 26, 618247
Mitochondrial disorders v1.335 NDUFA6 Sarah Leigh Classified gene: NDUFA6 as Green List (high evidence)
Mitochondrial disorders v1.335 NDUFA6 Sarah Leigh Added comment: Comment on list classification: This gene was added as Green due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter (May 2019) on behalf of GMS mitochondrial specialist test group: PMID: 30245030 reports four unrelated children who presented with neuroradiological findings and/or elevated lactate levels, with biallelic variants in this gene, plus functional studies.
From panels: Possible mitochondrial disorder - nuclear genes (Version 0.187) and Mitochondrial disorder with complex I deficiency (Version 0.65).
Mitochondrial disorders v1.335 NDUFA6 Sarah Leigh Gene: ndufa6 has been classified as Green List (High Evidence).
Mitochondrial disorders v1.334 NDUFA6 Sarah Leigh Phenotypes for gene: NDUFA6 were changed from Isolated complex I deficiency; Mitochondrial complex I deficiency, nuclear type 33, 618253 to Mitochondrial complex I deficiency, nuclear type 33, 618253
Mitochondrial disorders v1.333 NDUFA4 Sarah Leigh Added comment: Comment on phenotypes: No OMIM phenotype (23/05/2019).
Mitochondrial disorders v1.333 NDUFA4 Sarah Leigh Phenotypes for gene: NDUFA4 were changed from Isolated complex IV deficiency; No OMIM phenotype to Isolated complex IV deficiency; No OMIM phenotype
Possible mitochondrial disorder, nuclear genes v0.190 NDUFA4 Sarah Leigh Phenotypes for gene: NDUFA4 were changed from No OMIM phenotype to No OMIM phenotype; Mitochondrial complex IV deficiency
Mitochondrial disorders v1.332 NDUFA4 Sarah Leigh Publications for gene: NDUFA4 were set to PMID: 23746447
Mitochondrial disorders v1.331 NDUFA4 Sarah Leigh Mode of inheritance for gene: NDUFA4 was changed from to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v1.330 NDUFA4 Sarah Leigh Classified gene: NDUFA4 as Green List (high evidence)
Mitochondrial disorders v1.330 NDUFA4 Sarah Leigh Added comment: Comment on list classification: This gene was added as Green due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter (May 2019) on behalf of GMS mitochondrial specialist test group: 1 family (4 affecteds) reported with functional studies; also London team have diagnosed a second unrelated family; note that this is a Complex IV subunit.
From panel: Possible mitochondrial disorder - nuclear genes (Version 0.187).
Mitochondrial disorders v1.330 NDUFA4 Sarah Leigh Gene: ndufa4 has been classified as Green List (High Evidence).
Mitochondrial disorders v1.329 MSTO1 Sarah Leigh Phenotypes for gene: MSTO1 were changed from to Myopathy, mitochondrial, and ataxia, 617675
Mitochondrial disorders v1.328 MSTO1 Sarah Leigh Publications for gene: MSTO1 were set to
Mitochondrial disorders v1.327 MSTO1 Sarah Leigh Mode of inheritance for gene: MSTO1 was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mitochondrial disorders v1.326 MSTO1 Sarah Leigh Classified gene: MSTO1 as Green List (high evidence)
Mitochondrial disorders v1.326 MSTO1 Sarah Leigh Added comment: Comment on list classification: This gene was added as Green due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter (May 2019) on behalf of GMS mitochondrial specialist test group: 4 unrelated recessive families with functional studies; 1 dominant family with functional studies.
From panel: Possible mitochondrial disorder - nuclear genes (Version 0.187).
Mitochondrial disorders v1.326 MSTO1 Sarah Leigh Gene: msto1 has been classified as Green List (High Evidence).
Mitochondrial disorders v1.325 MRPS2 Sarah Leigh Phenotypes for gene: MRPS2 were changed from No OMIM phenotype to Combined oxidative phosphorylation deficiency 36 617950
Mitochondrial disorders v1.324 MRPS2 Sarah Leigh Publications for gene: MRPS2 were set to
Mitochondrial disorders v1.323 MRPS2 Sarah Leigh Mode of inheritance for gene: MRPS2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v1.322 MRPS2 Sarah Leigh Classified gene: MRPS2 as Green List (high evidence)
Mitochondrial disorders v1.322 MRPS2 Sarah Leigh Added comment: Comment on list classification: This gene was added as Green due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter (May 2019) on behalf of GMS mitochondrial specialist test group: 2 unrelated cases with functional studies.
From panel: Possible mitochondrial disorder - nuclear genes (Version 0.187).
Mitochondrial disorders v1.322 MRPS2 Sarah Leigh Gene: mrps2 has been classified as Green List (High Evidence).
Mitochondrial disorders v1.321 MRPL3 Sarah Leigh Phenotypes for gene: MRPL3 were changed from Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Combined oxidative phosphorylation deficiency 9, 614582 to Combined oxidative phosphorylation deficiency 9, 614582
Mitochondrial disorders v1.320 MRPL3 Sarah Leigh Classified gene: MRPL3 as Green List (high evidence)
Mitochondrial disorders v1.320 MRPL3 Sarah Leigh Added comment: Comment on list classification: This gene was added as Green due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter (May 2019) on behalf of GMS mitochondrial specialist test group: 2 unrelated families (4 sibs + 1 unrelated case) and functional studies.
From panel: Possible mitochondrial disorder - nuclear genes (Version 0.187).
Mitochondrial disorders v1.320 MRPL3 Sarah Leigh Gene: mrpl3 has been classified as Green List (High Evidence).
Mitochondrial disorders v1.319 FDX2 Sarah Leigh Classified gene: FDX2 as Green List (high evidence)
Mitochondrial disorders v1.319 FDX2 Sarah Leigh Added comment: Comment on list classification: This gene was added as Green due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter (May 2019) on behalf of GMS mitochondrial specialist test group: 3 unrelated familties; iron sulfur pathway.
From panel: Possible mitochondrial disorder - nuclear genes (Version 0.187).
Mitochondrial disorders v1.319 FDX2 Sarah Leigh Gene: fdx2 has been classified as Green List (High Evidence).
Possible mitochondrial disorder, nuclear genes v0.189 FDX2 Sarah Leigh Added comment: Comment on phenotypes: New phenotype added to OMIM on 25th March 2019.
Possible mitochondrial disorder, nuclear genes v0.189 FDX2 Sarah Leigh Phenotypes for gene: FDX2 were changed from No OMIM phenotype to Mitochondrial myopathy, episodic, with optic atrophy and reversible leukoencephalopathy, 251900
Mitochondrial disorders v1.318 FDX2 Sarah Leigh Publications for gene: FDX2 were set to 30010796; 24281368
Mitochondrial disorders v1.317 DNM2 Sarah Leigh Classified gene: DNM2 as Green List (high evidence)
Mitochondrial disorders v1.317 DNM2 Sarah Leigh Added comment: Comment on list classification: This gene was added as Green due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter (May 2019) on behalf of GMS mitochondrial specialist test group: 1 case with multiple deletions and COX negative fibres; 5 cases presented in a poster with dominant DMN2 variants (had COX deficient muscle fibres, one case with the p.Arg369Trp revealed disruption of the dynamic mitochondrial network, https://doi.org/10.1016/j.nmd.2012.06.124).
From panel: Possible mitochondrial disorder - nuclear genes (Version 0.187).
Mitochondrial disorders v1.317 DNM2 Sarah Leigh Gene: dnm2 has been classified as Green List (High Evidence).
Mitochondrial disorders v1.316 DNM2 Sarah Leigh Phenotypes for gene: DNM2 were changed from Disorders of mitochondrial DNA maintenance and integrity to Centronuclear myopathy 1, 160150; Charcot-Marie-Tooth disease, axonal type 2M, 606482; Charcot-Marie-Tooth disease, dominant intermediate B, 606482
Mitochondrial disorders v1.315 DNM2 Sarah Leigh Publications for gene: DNM2 were set to 23813975
Mitochondrial disorders v1.314 DNM2 Sarah Leigh Mode of inheritance for gene: DNM2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mitochondrial disorders v1.313 COQ7 Sarah Leigh Classified gene: COQ7 as Green List (high evidence)
Mitochondrial disorders v1.313 COQ7 Sarah Leigh Added comment: Comment on list classification: This gene was added as Green due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter (May 2019) on behalf of GMS mitochondrial specialist test group: 3 unrelated individuals and functional studies.
From panel: Possible mitochondrial disorder - nuclear genes (Version 0.187).
Mitochondrial disorders v1.313 COQ7 Sarah Leigh Gene: coq7 has been classified as Green List (High Evidence).
Mitochondrial disorders v1.312 COQ7 Sarah Leigh Publications for gene: COQ7 were set to 26084283; 28409910
Mitochondrial disorder with complex IV deficiency v0.41 COA7 Sarah Leigh Added comment: Comment on phenotypes: ?Mitochondrial complex IV deficiency, 220110 has been removed from this gene as COA7 is not associated with this phenotype.
Mitochondrial disorder with complex IV deficiency v0.41 COA7 Sarah Leigh Phenotypes for gene: COA7 were changed from ?Mitochondrial complex IV deficiency, 220110; Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3, 618387 to Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3, 618387
Possible mitochondrial disorder, nuclear genes v0.188 COA7 Sarah Leigh Added comment: Comment on phenotypes: ?Mitochondrial complex IV deficiency, 220110 has been removed from this gene as COA7 is not associated with this phenotype.
Possible mitochondrial disorder, nuclear genes v0.188 COA7 Sarah Leigh Phenotypes for gene: COA7 were changed from ?Mitochondrial complex IV deficiency, 220110; Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3, 618387 to Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3, 618387
Mitochondrial disorders v1.311 COA7 Sarah Leigh Publications for gene: COA7 were set to
Mitochondrial disorders v1.310 COA7 Sarah Leigh Mode of inheritance for gene: COA7 was changed from to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v1.309 COA7 Sarah Leigh Classified gene: COA7 as Green List (high evidence)
Mitochondrial disorders v1.309 COA7 Sarah Leigh Added comment: Comment on list classification: This gene was added as Green due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter (May 2019) on behalf of GMS mitochondrial specialist test group: Several unrelated cases and functional studies.
From panels: Possible mitochondrial disorder - nuclear genes (Version 0.187) and Mitochondrial disorder with complex IV deficiency (Version 0.40).
Mitochondrial disorders v1.309 COA7 Sarah Leigh Gene: coa7 has been classified as Green List (High Evidence).
Mitochondrial disorders v1.308 COA6 Sarah Leigh Classified gene: COA6 as Green List (high evidence)
Mitochondrial disorders v1.308 COA6 Sarah Leigh Added comment: Comment on list classification: This gene was added as Green due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter (May 2019) on behalf of GMS mitochondrial specialist test group: 2 cases from 2 unrelated families and functional studies.
From panel: Possible mitochondrial disorder - nuclear genes (Version 0.187).
Mitochondrial disorders v1.308 COA6 Sarah Leigh Gene: coa6 has been classified as Green List (High Evidence).
Fetal anomalies v0.252 ATP7A Rebecca Foulger Publications for gene: ATP7A were set to
Fetal anomalies v0.251 HEXA Rebecca Foulger Publications for gene: HEXA were set to
Mitochondrial disorders v1.307 COA6 Sarah Leigh Phenotypes for gene: COA6 were changed from ?{Fatal infantile cardiomyopathy, association with}, 604377 to Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 4 616501
Mitochondrial disorders v1.306 COA6 Sarah Leigh Publications for gene: COA6 were set to
Mitochondrial disorders v1.305 CA5A Sarah Leigh Phenotypes for gene: CA5A were changed from to Hyperammonemia due to carbonic anhydrase VA deficiency, 615751
Mitochondrial disorders v1.304 CA5A Sarah Leigh Publications for gene: CA5A were set to
Mitochondrial disorders v1.303 CA5A Sarah Leigh Mode of inheritance for gene: CA5A was changed from to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v1.302 CA5A Sarah Leigh Classified gene: CA5A as Green List (high evidence)
Mitochondrial disorders v1.302 CA5A Sarah Leigh Added comment: Comment on list classification: This gene was added as Green due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter (May 2019) on behalf of GMS mitochondrial specialist test group: Multiple unrelated families; discussed & agreed that this should be included within 'primary mitochondrial disease' (symptoms include hyperammonemia, hyperlactatemia and ketonuria).
Mitochondrial disorders v1.302 CA5A Sarah Leigh Gene: ca5a has been classified as Green List (High Evidence).
Monogenic hearing loss v1.108 MT-TS1 Eleanor Williams Publications for gene: MT-TS1 were set to PMID:10094190; 10340654; 10371545; 10545608; 10978361; 11069477; 11175301; 11378827; 12461693; 127819; 14605505; 17659260; 20153673; 6213205; 7219534; 7581383; 7669057; 7987332; 8019558; 8572257; 9450881; 9742104; 9832034
Early onset or syndromic epilepsy v1.52 RALA Eleanor Williams Added comment: Comment on publications: 10.1371/journal.pgen.1007671 is PMID: 30500825
Early onset or syndromic epilepsy v1.52 RALA Eleanor Williams Publications for gene: RALA were set to doi.org/10.1371/journal.pgen.1007671
Hereditary spastic paraplegia, adult onset v0.151 TBP_CAG Louise Daugherty commented on STR: TBP_CAG: STR reviewed and discussed at the GMS Neurology Specialist Test Group Webex on 17th May 2019, agreed to leave rating as Green.
Hereditary spastic paraplegia, adult onset v0.151 PPP2R2B_CAG Louise Daugherty edited their review of STR: PPP2R2B_CAG: Added comment: STR reviewed and discussed at the GMS Neurology Specialist Test Group Webex on 17th May 2019, agreed to leave rating as Green.; Changed rating: GREEN
Hereditary spastic paraplegia, adult onset v0.151 FXN_GAA Louise Daugherty edited their review of STR: FXN_GAA: Added comment: STR reviewed and discussed at the GMS Neurology Specialist Test Group Webex on 17th May 2019, agreed to leave rating as Green.; Changed rating: GREEN
Hereditary spastic paraplegia, adult onset v0.151 CACNA1A_CAG Louise Daugherty commented on STR: CACNA1A_CAG: STR reviewed and discussed at the GMS Neurology Specialist Test Group Webex on 17th May 2019, agreed to leave rating as Green.
Hereditary spastic paraplegia, adult onset v0.151 ATXN7_CAG Louise Daugherty commented on STR: ATXN7_CAG: STR reviewed and discussed at the GMS Neurology Specialist Test Group Webex on 17th May 2019, agreed to leave rating as Green.
Hereditary spastic paraplegia, adult onset v0.151 ATXN3_CAG Louise Daugherty edited their review of STR: ATXN3_CAG: Added comment: STR reviewed and discussed at the GMS Neurology Specialist Test Group Webex on 17th May 2019, agreed to leave rating as Green.; Changed rating: GREEN
Hereditary spastic paraplegia, adult onset v0.151 ATXN2_CAG Louise Daugherty commented on STR: ATXN2_CAG: STR reviewed and discussed at the GMS Neurology Specialist Test Group Webex on 17th May 2019, agreed to leave rating as Green.
Hereditary spastic paraplegia, adult onset v0.151 ATXN1_CAG Louise Daugherty edited their review of STR: ATXN1_CAG: Added comment: STR reviewed and discussed at the GMS Neurology Specialist Test Group Webex on 17th May 2019, agreed to leave rating as Green.; Changed rating: GREEN
Hereditary spastic paraplegia, childhood onset v1.177 PPP2R2B_CAG Louise Daugherty edited their review of STR: PPP2R2B_CAG: Changed rating: AMBER
Hereditary spastic paraplegia, childhood onset v1.177 HTT_CAG Louise Daugherty edited their review of STR: HTT_CAG: Changed rating: AMBER
Hereditary spastic paraplegia, childhood onset v1.177 CACNA1A_CAG Louise Daugherty edited their review of STR: CACNA1A_CAG: Changed rating: AMBER
Hereditary spastic paraplegia, childhood onset v1.177 ATXN7_CAG Louise Daugherty edited their review of STR: ATXN7_CAG: Changed rating: AMBER
Hereditary spastic paraplegia, childhood onset v1.177 ATXN3_CAG Louise Daugherty edited their review of STR: ATXN3_CAG: Changed rating: AMBER
Hereditary spastic paraplegia, childhood onset v1.177 ATXN2_CAG Louise Daugherty edited their review of STR: ATXN2_CAG: Changed rating: AMBER
Hereditary spastic paraplegia, childhood onset v1.177 ATXN1_CAG Louise Daugherty edited their review of STR: ATXN1_CAG: Changed rating: AMBER
Hereditary spastic paraplegia, childhood onset v1.177 ATXN10_ATTCT Louise Daugherty edited their review of STR: ATXN10_ATTCT: Changed rating: AMBER
Hereditary spastic paraplegia, adult onset v0.151 ATXN10_ATTCT Louise Daugherty edited their review of STR: ATXN10_ATTCT: Added comment: STR reviewed and discussed at the GMS Neurology Specialist Test Group Webex on 17th May 2019, agreed to leave rating as Green.; Changed rating: GREEN
Hereditary spastic paraplegia, adult onset v0.151 HTT_CAG Louise Daugherty Classified STR: HTT_CAG as Amber List (moderate evidence)
Hereditary spastic paraplegia, adult onset v0.151 HTT_CAG Louise Daugherty Added comment: Comment on list classification: STR reviewed and discussed at the GMS Neurology Specialist Test Group Webex on 17th May Agreed to change the rating from Green to Amber. Further comment: risk element- needs further discussion from data analysis from 100K Genomes Project.
Hereditary spastic paraplegia, adult onset v0.151 HTT_CAG Louise Daugherty Str: htt_cag has been classified as Amber List (Moderate Evidence).
Hereditary spastic paraplegia, childhood onset v1.177 TBP_CAG Louise Daugherty Classified STR: TBP_CAG as Amber List (moderate evidence)
Hereditary spastic paraplegia, childhood onset v1.177 TBP_CAG Louise Daugherty Added comment: Comment on list classification: STR reviewed and discussed at the GMS Neurology Specialist Test Group Webex on 17th May Agreed to change the rating from Green to Amber.
Hereditary spastic paraplegia, childhood onset v1.177 TBP_CAG Louise Daugherty Str: tbp_cag has been classified as Amber List (Moderate Evidence).
Hereditary spastic paraplegia, childhood onset v1.176 PPP2R2B_CAG Louise Daugherty Classified STR: PPP2R2B_CAG as Amber List (moderate evidence)
Hereditary spastic paraplegia, childhood onset v1.176 PPP2R2B_CAG Louise Daugherty Added comment: Comment on list classification: STR reviewed and discussed at the GMS Neurology Specialist Test Group Webex on 17th May Agreed to change the rating from Green to Amber.
Hereditary spastic paraplegia, childhood onset v1.176 PPP2R2B_CAG Louise Daugherty Str: ppp2r2b_cag has been classified as Amber List (Moderate Evidence).
Hereditary spastic paraplegia, childhood onset v1.175 HTT_CAG Louise Daugherty Classified STR: HTT_CAG as Amber List (moderate evidence)
Hereditary spastic paraplegia, childhood onset v1.175 HTT_CAG Louise Daugherty Added comment: Comment on list classification: STR reviewed and discussed at the GMS Neurology Specialist Test Group Webex on 17th May Agreed to change the rating from Green to Amber. Further comment: risk element- needs further discussion from data analysis from 100K Genomes Project.
Hereditary spastic paraplegia, childhood onset v1.175 HTT_CAG Louise Daugherty Str: htt_cag has been classified as Amber List (Moderate Evidence).
Hereditary spastic paraplegia, childhood onset v1.174 CACNA1A_CAG Louise Daugherty Classified STR: CACNA1A_CAG as Amber List (moderate evidence)
Hereditary spastic paraplegia, childhood onset v1.174 CACNA1A_CAG Louise Daugherty Added comment: Comment on list classification: STR reviewed and discussed at the GMS Neurology Specialist Test Group Webex on 17th May Agreed to change the rating from Green to Amber.
Hereditary spastic paraplegia, childhood onset v1.174 CACNA1A_CAG Louise Daugherty Str: cacna1a_cag has been classified as Amber List (Moderate Evidence).
Hereditary spastic paraplegia, childhood onset v1.173 ATXN7_CAG Louise Daugherty Classified STR: ATXN7_CAG as Amber List (moderate evidence)
Hereditary spastic paraplegia, childhood onset v1.173 ATXN7_CAG Louise Daugherty Added comment: Comment on list classification: STR reviewed and discussed at the GMS Neurology Specialist Test Group Webex on 17th May Agreed to change the rating from Green to Amber.
Hereditary spastic paraplegia, childhood onset v1.173 ATXN7_CAG Louise Daugherty Str: atxn7_cag has been classified as Amber List (Moderate Evidence).
Hereditary spastic paraplegia, childhood onset v1.172 ATXN3_CAG Louise Daugherty Classified STR: ATXN3_CAG as Amber List (moderate evidence)
Hereditary spastic paraplegia, childhood onset v1.172 ATXN3_CAG Louise Daugherty Added comment: Comment on list classification: STR reviewed and discussed at the GMS Neurology Specialist Test Group Webex on 17th May Agreed to change the rating from Green to Amber.
Hereditary spastic paraplegia, childhood onset v1.172 ATXN3_CAG Louise Daugherty Str: atxn3_cag has been classified as Amber List (Moderate Evidence).
Hereditary spastic paraplegia, childhood onset v1.171 ATXN2_CAG Louise Daugherty Classified STR: ATXN2_CAG as Amber List (moderate evidence)
Hereditary spastic paraplegia, childhood onset v1.171 ATXN2_CAG Louise Daugherty Added comment: Comment on list classification: STR reviewed and discussed at the GMS Neurology Specialist Test Group Webex on 17th May Agreed to change the rating from Green to Amber.
Hereditary spastic paraplegia, childhood onset v1.171 ATXN2_CAG Louise Daugherty Str: atxn2_cag has been classified as Amber List (Moderate Evidence).
Hereditary spastic paraplegia, childhood onset v1.170 ATXN1_CAG Louise Daugherty Classified STR: ATXN1_CAG as Amber List (moderate evidence)
Hereditary spastic paraplegia, childhood onset v1.170 ATXN1_CAG Louise Daugherty Added comment: Comment on list classification: STR reviewed and discussed at the GMS Neurology Specialist Test Group Webex on 17th May Agreed to change the rating from Green to Amber.
Hereditary spastic paraplegia, childhood onset v1.170 ATXN1_CAG Louise Daugherty Str: atxn1_cag has been classified as Amber List (Moderate Evidence).
Hereditary spastic paraplegia, childhood onset v1.169 FXN_GAA Louise Daugherty commented on STR: FXN_GAA: STR reviewed and discussed at the GMS Neurology Specialist Test Group Webex on 17th May. Agreed to leave rating as Green.
Hereditary spastic paraplegia, childhood onset v1.169 ATXN10_ATTCT Louise Daugherty Classified STR: ATXN10_ATTCT as Amber List (moderate evidence)
Hereditary spastic paraplegia, childhood onset v1.169 ATXN10_ATTCT Louise Daugherty Added comment: Comment on list classification: STR reviewed and discussed at the GMS Neurology Specialist Test Group Webex on 17th May 2019. Agreed to change the rating from Green to Amber.
Hereditary spastic paraplegia, childhood onset v1.169 ATXN10_ATTCT Louise Daugherty Str: atxn10_attct has been classified as Amber List (Moderate Evidence).
Hereditary spastic paraplegia, adult onset v0.150 FXN Louise Daugherty Classified gene: FXN as Green List (high evidence)
Hereditary spastic paraplegia, adult onset v0.150 FXN Louise Daugherty Gene: fxn has been classified as Green List (High Evidence).
Hereditary spastic paraplegia, childhood onset v1.168 FXN Louise Daugherty Classified gene: FXN as Green List (high evidence)
Hereditary spastic paraplegia, childhood onset v1.168 FXN Louise Daugherty Gene: fxn has been classified as Green List (High Evidence).
Hereditary spastic paraplegia, adult onset v0.149 FXN Louise Daugherty gene: FXN was added
gene: FXN was added to Hereditary spastic paraplegia - adult onset. Sources: Expert Review
Mode of inheritance for gene: FXN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FXN were set to 8596916; 9150176; 9737785; 21830088
Phenotypes for gene: FXN were set to Friedreich ataxia, 229300
Review for gene: FXN was set to GREEN
Added comment: New Green gene added and agreed from the GMS Neurology Specialist Test Group Webex on 17th May 2019. Single nucleotide variants can cause the disease (often compound het STR + SNV)
Sources: Expert Review
Hereditary spastic paraplegia, childhood onset v1.167 FXN Louise Daugherty gene: FXN was added
gene: FXN was added to Hereditary spastic paraplegia - childhood onset. Sources: Expert Review
Mode of inheritance for gene: FXN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FXN were set to 8596916; 9150176; 9737785; 21830088
Phenotypes for gene: FXN were set to Friedreich ataxia, 229300
Review for gene: FXN was set to GREEN
Added comment: New Green gene added and agreed from the GMS Neurology Specialist Test Group Webex on 17th May 2019. Single nucleotide variants can cause the disease (often compound het STR + SNV)
Sources: Expert Review
Retinal disorders v1.139 REEP6 Andrew Webster gene: REEP6 was added
gene: REEP6 was added to Retinal disorders. Sources: Literature
Mode of inheritance for gene: REEP6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: REEP6 were set to PMID: 30101608; 28475715; 28369466; 27889058; 24691551
Phenotypes for gene: REEP6 were set to retinitis pigmentosa
Penetrance for gene: REEP6 were set to Complete
Review for gene: REEP6 was set to GREEN
Added comment: Sources: Literature
Hereditary spastic paraplegia, childhood onset v1.166 WDR48 Louise Daugherty reviewed gene: WDR48: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary spastic paraplegia, childhood onset v1.166 VPS37A Louise Daugherty commented on gene: VPS37A: Red gene with Green GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Amber rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, childhood onset v1.166 VAMP1 Louise Daugherty commented on gene: VAMP1: Red gene with Green and Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Amber rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, childhood onset v1.166 TFG Louise Daugherty commented on gene: TFG: Amber gene with Green GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, childhood onset v1.166 TECPR2 Louise Daugherty commented on gene: TECPR2: Red gene with Green and Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Amber rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, childhood onset v1.166 SLC33A1 Louise Daugherty commented on gene: SLC33A1: Amber gene with Green and Red GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Red rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, childhood onset v1.166 SLC25A46 Louise Daugherty commented on gene: SLC25A46: Green gene with Red GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Amber rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, childhood onset v1.166 REEP2 Louise Daugherty commented on gene: REEP2: Amber gene with Green GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, childhood onset v1.166 PSEN1 Louise Daugherty commented on gene: PSEN1: Red gene with Green GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Red rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, childhood onset v1.166 POLR3A Louise Daugherty commented on gene: POLR3A: Green gene with Red GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, childhood onset v1.166 MTPAP Louise Daugherty commented on gene: MTPAP: Amber gene with Green GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Amber rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, childhood onset v1.166 MARS2 Louise Daugherty commented on gene: MARS2: Amber gene with Green GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Amber rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, childhood onset v1.166 MAG Louise Daugherty commented on gene: MAG: Amber gene with Green GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Amber rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, childhood onset v1.166 LYST Louise Daugherty commented on gene: LYST: Amber gene with Green GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Amber rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, childhood onset v1.166 KIF1C Louise Daugherty commented on gene: KIF1C: Amber gene with Green GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, childhood onset v1.166 KDM5C Louise Daugherty commented on gene: KDM5C: Amber gene with Green GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, childhood onset v1.166 IBA57 Louise Daugherty commented on gene: IBA57: Amber gene with Green GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Amber rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, childhood onset v1.166 GJC2 Louise Daugherty commented on gene: GJC2: Red gene with Green GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Amber rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, childhood onset v1.166 GCH1 Louise Daugherty commented on gene: GCH1: Amber gene with Green GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, childhood onset v1.166 GAD1 Louise Daugherty reviewed gene: GAD1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary spastic paraplegia, childhood onset v1.166 ENTPD1 Louise Daugherty reviewed gene: ENTPD1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary spastic paraplegia, childhood onset v1.166 DSTYK Louise Daugherty commented on gene: DSTYK: Red gene with Green and Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Amber rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, childhood onset v1.166 DARS Louise Daugherty commented on gene: DARS: Amber gene with Green GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, childhood onset v1.166 CDK16 Louise Daugherty commented on gene: CDK16: Amber gene with Red GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Red rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, childhood onset v1.166 CAPN1 Louise Daugherty commented on gene: CAPN1: Amber gene with Green GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, childhood onset v1.166 ARL6IP1 Louise Daugherty reviewed gene: ARL6IP1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary spastic paraplegia, childhood onset v1.166 AP5Z1 Louise Daugherty commented on gene: AP5Z1: Amber gene with Green GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, childhood onset v1.166 AMPD2 Louise Daugherty commented on gene: AMPD2: Amber gene with Green GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Amber rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, childhood onset v1.165 WDR48 Louise Daugherty Source Expert Review Amber was added to WDR48.
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Hereditary spastic paraplegia, childhood onset v1.165 VPS37A Louise Daugherty Source Expert Review Amber was added to VPS37A.
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Hereditary spastic paraplegia, childhood onset v1.165 VAMP1 Louise Daugherty Source Expert Review Amber was added to VAMP1.
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Hereditary spastic paraplegia, childhood onset v1.165 TFG Louise Daugherty Source Expert Review Green was added to TFG.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary spastic paraplegia, childhood onset v1.165 TECPR2 Louise Daugherty Source Expert Review Amber was added to TECPR2.
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Hereditary spastic paraplegia, childhood onset v1.165 SLC33A1 Louise Daugherty Source Expert Review Red was added to SLC33A1.
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Hereditary spastic paraplegia, childhood onset v1.165 SLC25A46 Louise Daugherty Source Expert Review Amber was added to SLC25A46.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Hereditary spastic paraplegia, childhood onset v1.165 REEP2 Louise Daugherty Source Expert Review Green was added to REEP2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary spastic paraplegia, childhood onset v1.165 KIF1C Louise Daugherty Source Expert Review Green was added to KIF1C.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary spastic paraplegia, childhood onset v1.165 KDM5C Louise Daugherty Source Expert Review Green was added to KDM5C.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary spastic paraplegia, childhood onset v1.165 GJC2 Louise Daugherty Source Expert Review Amber was added to GJC2.
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Hereditary spastic paraplegia, childhood onset v1.165 GCH1 Louise Daugherty Source Expert Review Green was added to GCH1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary spastic paraplegia, childhood onset v1.165 GAD1 Louise Daugherty Source Expert Review Amber was added to GAD1.
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Hereditary spastic paraplegia, childhood onset v1.165 ENTPD1 Louise Daugherty Source Expert Review Green was added to ENTPD1.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Hereditary spastic paraplegia, childhood onset v1.165 DSTYK Louise Daugherty Source Expert Review Amber was added to DSTYK.
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Hereditary spastic paraplegia, childhood onset v1.165 DARS Louise Daugherty Source Expert Review Green was added to DARS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary spastic paraplegia, childhood onset v1.165 CDK16 Louise Daugherty Source Expert Review Red was added to CDK16.
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Hereditary spastic paraplegia, childhood onset v1.165 CAPN1 Louise Daugherty Source Expert Review Green was added to CAPN1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary spastic paraplegia, childhood onset v1.165 ARL6IP1 Louise Daugherty Source Expert Review Amber was added to ARL6IP1.
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Hereditary spastic paraplegia, childhood onset v1.165 AP5Z1 Louise Daugherty Source Expert Review Green was added to AP5Z1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v1.301 C19orf70 Sarah Leigh Phenotypes for gene: C19orf70 were changed from to Combined oxidative phosphorylation deficiency 37, 618329
Mitochondrial disorders v1.300 C19orf70 Sarah Leigh Publications for gene: C19orf70 were set to
Mitochondrial disorders v1.299 C19orf70 Sarah Leigh Mode of inheritance for gene: C19orf70 was changed from to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v1.298 C19orf70 Sarah Leigh commented on gene: C19orf70: New gene symbol: MICOS13
Possible mitochondrial disorder, nuclear genes v0.187 C19orf70 Sarah Leigh Deleted their review
Possible mitochondrial disorder, nuclear genes v0.187 C19orf70 Sarah Leigh Deleted their comment
Possible mitochondrial disorder, nuclear genes v0.187 C19orf70 Sarah Leigh commented on gene: C19orf70
Mitochondrial disorders v1.298 C19orf70 Sarah Leigh Tag new-gene-name tag was added to gene: C19orf70.
Mitochondrial disorders v1.298 C19orf70 Sarah Leigh Classified gene: C19orf70 as Green List (high evidence)
Mitochondrial disorders v1.298 C19orf70 Sarah Leigh Added comment: Comment on list classification: This gene was added as Green due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter (May 2019) on behalf of GMS mitochondrial specialist test group: 3 unrelated families (2sibs, 2sibs, 1) and functional studies
Mitochondrial disorders v1.298 C19orf70 Sarah Leigh Gene: c19orf70 has been classified as Green List (High Evidence).
Hereditary spastic paraplegia, adult onset v0.148 WDR45B Louise Daugherty commented on gene: WDR45B: Green gene with Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 VPS37A Louise Daugherty commented on gene: VPS37A: Green gene with Red GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Amber rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 VAMP1 Louise Daugherty commented on gene: VAMP1: Green gene with Red and Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Amber rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 UCHL1 Louise Daugherty commented on gene: UCHL1: Green gene with Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 TECPR2 Louise Daugherty commented on gene: TECPR2: Green gene with Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Amber rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 SPART Louise Daugherty commented on gene: SPART: Green gene with Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 SLC33A1 Louise Daugherty commented on gene: SLC33A1: Green gene with Red GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Red rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 SLC1A4 Louise Daugherty commented on gene: SLC1A4: Green gene with Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 SLC16A2 Louise Daugherty commented on gene: SLC16A2: Green gene with Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 SERAC1 Louise Daugherty commented on gene: SERAC1: Green gene with Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 REEP2 Louise Daugherty commented on gene: REEP2: Green gene with Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 PSEN1 Louise Daugherty commented on gene: PSEN1: Green gene with Red GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 POLR3A Louise Daugherty commented on gene: POLR3A: Red gene with Green GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 NT5C2 Louise Daugherty commented on gene: NT5C2: Green gene with Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 NKX6-2 Louise Daugherty commented on gene: NKX6-2: Green gene with Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 MTPAP Louise Daugherty commented on gene: MTPAP: Green gene with Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Amber rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 MARS2 Louise Daugherty commented on gene: MARS2: Green gene with Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Amber rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 MAG Louise Daugherty commented on gene: MAG: Green gene with Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Amber rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 LYST Louise Daugherty commented on gene: LYST: Green gene with Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Amber rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 L1CAM Louise Daugherty commented on gene: L1CAM: Green gene with Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 KIF1C Louise Daugherty commented on gene: KIF1C: Green gene with Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 KIDINS220 Louise Daugherty commented on gene: KIDINS220: Green gene with Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 KDM5C Louise Daugherty commented on gene: KDM5C: Green gene with Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 IBA57 Louise Daugherty commented on gene: IBA57: Green gene with Red and Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Amber rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 HACE1 Louise Daugherty commented on gene: HACE1: Green gene with Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 GJC2 Louise Daugherty commented on gene: GJC2: Green gene with Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Amber rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 GCH1 Louise Daugherty commented on gene: GCH1: Green gene with Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 FARS2 Louise Daugherty commented on gene: FARS2: Green gene with Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 ERLIN1 Louise Daugherty commented on gene: ERLIN1: Green gene with Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 ENTPD1 Louise Daugherty commented on gene: ENTPD1: Amber gene with Green GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 DSTYK Louise Daugherty commented on gene: DSTYK: Green gene with Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Amber rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 DARS Louise Daugherty commented on gene: DARS: Green gene with Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 CYP2U1 Louise Daugherty commented on gene: CYP2U1: Green gene with Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 CPT1C Louise Daugherty commented on gene: CPT1C: Green gene with Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Amber rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 C19orf12 Louise Daugherty commented on gene: C19orf12: Green gene with Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 C12orf65 Louise Daugherty commented on gene: C12orf65: Green gene with Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 BSCL2 Louise Daugherty commented on gene: BSCL2: Green gene with Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 ATP13A2 Louise Daugherty commented on gene: ATP13A2: Green gene with Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 ARG1 Louise Daugherty commented on gene: ARG1: Green gene with Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 AP4S1 Louise Daugherty commented on gene: AP4S1: Green gene with Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 AP4M1 Louise Daugherty commented on gene: AP4M1: Green gene with Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 AP4E1 Louise Daugherty commented on gene: AP4E1: Green gene with Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 AP4B1 Louise Daugherty commented on gene: AP4B1: Green gene with Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 AMPD2 Louise Daugherty commented on gene: AMPD2: Green gene with Red and Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Amber rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 ALS2 Louise Daugherty commented on gene: ALS2: Green gene with Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 AIMP1 Louise Daugherty commented on gene: AIMP1: Green gene with Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 AFG3L2 Louise Daugherty commented on gene: AFG3L2: Green gene with Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Hereditary spastic paraplegia, adult onset v0.148 ADAR Louise Daugherty commented on gene: ADAR: Green gene with Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.121 SIX1 Eleanor Williams Classified gene: SIX1 as Amber List (moderate evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.121 SIX1 Eleanor Williams Added comment: Comment on list classification: Upgrading from red to amber. Amber rating agreed at the GMS musculoskeletal specialist test group Webex on 2019-05-13. The group decided to rate Amber due to several unpublished cases.
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.121 SIX1 Eleanor Williams Gene: six1 has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v1.297 ATP5D Sarah Leigh Classified gene: ATP5D as Green List (high evidence)
Mitochondrial disorders v1.297 ATP5D Sarah Leigh Added comment: Comment on list classification: This gene was promoted from Amber to Green due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter (May 2019) on behalf of GMS mitochondrial specialist test group: 2 unrelated children and functional studies.
Mitochondrial disorders v1.297 ATP5D Sarah Leigh Gene: atp5d has been classified as Green List (High Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.120 PRRX1 Eleanor Williams Classified gene: PRRX1 as Amber List (moderate evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.120 PRRX1 Eleanor Williams Added comment: Comment on list classification: Upgrading from red to amber. Amber rating agreed at the GMS musculoskeletal specialist test group Webex on 2019-05-13. The group decided to rate Amber due to several unpublished cases.
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.120 PRRX1 Eleanor Williams Gene: prrx1 has been classified as Amber List (Moderate Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.119 B3GAT3 Eleanor Williams Classified gene: B3GAT3 as Amber List (moderate evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.119 B3GAT3 Eleanor Williams Added comment: Comment on list classification: Upgrading from red to amber. Amber rating agreed at the GMS musculoskeletal specialist test group Webex on 2019-05-13. The group decided to rate amber until there is more evidence for the gene-disease association.
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.119 B3GAT3 Eleanor Williams Gene: b3gat3 has been classified as Amber List (Moderate Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.118 B3GAT3 Eleanor Williams Mode of inheritance for gene: B3GAT3 was changed from to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v1.296 ATP5D Sarah Leigh commented on gene: ATP5D
Hereditary spastic paraplegia, adult onset v0.147 VPS37A Louise Daugherty Source Expert Review Amber was added to VPS37A.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Hereditary spastic paraplegia, adult onset v0.147 VAMP1 Louise Daugherty Source Expert Review Amber was added to VAMP1.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Hereditary spastic paraplegia, adult onset v0.147 TECPR2 Louise Daugherty Source Expert Review Amber was added to TECPR2.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Hereditary spastic paraplegia, adult onset v0.147 SLC33A1 Louise Daugherty Source Expert Review Red was added to SLC33A1.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Hereditary spastic paraplegia, adult onset v0.147 POLR3A Louise Daugherty Source Expert Review Green was added to POLR3A.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Hereditary spastic paraplegia, adult onset v0.147 MTPAP Louise Daugherty Source Expert Review Amber was added to MTPAP.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Hereditary spastic paraplegia, adult onset v0.147 MARS2 Louise Daugherty Source Expert Review Amber was added to MARS2.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Hereditary spastic paraplegia, adult onset v0.147 MAG Louise Daugherty Source Expert Review Amber was added to MAG.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Hereditary spastic paraplegia, adult onset v0.147 LYST Louise Daugherty Source Expert Review Amber was added to LYST.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Hereditary spastic paraplegia, adult onset v0.147 IBA57 Louise Daugherty Source Expert Review Amber was added to IBA57.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Hereditary spastic paraplegia, adult onset v0.147 GJC2 Louise Daugherty Source Expert Review Amber was added to GJC2.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Hereditary spastic paraplegia, adult onset v0.147 ENTPD1 Louise Daugherty Source Expert Review Green was added to ENTPD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary spastic paraplegia, adult onset v0.147 DSTYK Louise Daugherty Source Expert Review Amber was added to DSTYK.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Hereditary spastic paraplegia, adult onset v0.147 CPT1C Louise Daugherty Source Expert Review Amber was added to CPT1C.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Hereditary spastic paraplegia, adult onset v0.147 AMPD2 Louise Daugherty Source Expert Review Amber was added to AMPD2.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Mitochondrial disorders v1.296 ATP5D Sarah Leigh Tag new-gene-name tag was added to gene: ATP5D.
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.117 PPP1CB Eleanor Williams Phenotypes for gene: PPP1CB were changed from to Noonan syndrome-like disorder with loose anagen hair 2 617506
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.116 PPP1CB Eleanor Williams Classified gene: PPP1CB as Amber List (moderate evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.116 PPP1CB Eleanor Williams Added comment: Comment on list classification: Upgrading from red to amber. Amber rating agreed at the GMS musculoskeletal specialist test group Webex on 2019-05-13. A Noonan syndrome-related gene, but the group decided it should be Amber as there is a less well-evidenced association with craniosynostosis than other Noonan genes
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.116 PPP1CB Eleanor Williams Gene: ppp1cb has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v1.296 ATP5D Sarah Leigh Phenotypes for gene: ATP5D were changed from to Mitochondrial complex V (ATP synthase) deficiency, 618120
Mitochondrial disorders v1.295 ATP5D Sarah Leigh Publications for gene: ATP5D were set to
Mitochondrial disorders v1.294 ATP5D Sarah Leigh Mode of inheritance for gene: ATP5D was changed from to BIALLELIC, autosomal or pseudoautosomal
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.115 PPP1CB Eleanor Williams gene: PPP1CB was added
gene: PPP1CB was added to Craniosynostosis. Sources: Expert list
Mode of inheritance for gene: PPP1CB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Review for gene: PPP1CB was set to AMBER
Added comment: Adding gene following GMS musculoskeletal specialist test group Webex on 2019-05-13. This is a known Noonan syndrome gene.
Sources: Expert list
Mitochondrial disorders v1.293 UQCRB Sarah Leigh Source NHS GMS was added to UQCRB.
Source Expert Review Green was added to UQCRB.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v1.293 UQCC2 Sarah Leigh Source NHS GMS was added to UQCC2.
Source Expert Review Green was added to UQCC2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v1.293 TRMT10C Sarah Leigh Source NHS GMS was added to TRMT10C.
Source Expert Review Green was added to TRMT10C.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Mitochondrial disorders v1.293 TOP3A Sarah Leigh Source NHS GMS was added to TOP3A.
Source Expert Review Green was added to TOP3A.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Mitochondrial disorders v1.293 SLC25A32 Sarah Leigh gene: SLC25A32 was added
gene: SLC25A32 was added to Mitochondrial disorders. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: SLC25A32 was set to
Mitochondrial disorders v1.293 SFXN4 Sarah Leigh Source NHS GMS was added to SFXN4.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Mitochondrial disorders v1.293 SDHD Sarah Leigh Source NHS GMS was added to SDHD.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Mitochondrial disorders v1.293 SDHAF1 Sarah Leigh Source NHS GMS was added to SDHAF1.
Source Expert Review Green was added to SDHAF1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Mitochondrial disorders v1.293 PNPLA8 Sarah Leigh Source NHS GMS was added to PNPLA8.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Mitochondrial disorders v1.293 PMPCB Sarah Leigh gene: PMPCB was added
gene: PMPCB was added to Mitochondrial disorders. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: PMPCB was set to
Mitochondrial disorders v1.293 NDUFB8 Sarah Leigh Source NHS GMS was added to NDUFB8.
Source Expert Review Green was added to NDUFB8.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Mitochondrial disorders v1.293 NDUFAF8 Sarah Leigh gene: NDUFAF8 was added
gene: NDUFAF8 was added to Mitochondrial disorders. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: NDUFAF8 was set to
Mitochondrial disorders v1.293 NDUFA9 Sarah Leigh Source NHS GMS was added to NDUFA9.
Source Expert Review Green was added to NDUFA9.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v1.293 NDUFA6 Sarah Leigh Source NHS GMS was added to NDUFA6.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Mitochondrial disorders v1.293 NDUFA4 Sarah Leigh Source NHS GMS was added to NDUFA4.
Source Expert Review Green was added to NDUFA4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v1.293 MSTO1 Sarah Leigh gene: MSTO1 was added
gene: MSTO1 was added to Mitochondrial disorders. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: MSTO1 was set to
Mitochondrial disorders v1.293 MRPS2 Sarah Leigh Source NHS GMS was added to MRPS2.
Source Expert Review Green was added to MRPS2.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Mitochondrial disorders v1.293 MRPL3 Sarah Leigh Source NHS GMS was added to MRPL3.
Source Expert Review Green was added to MRPL3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v1.293 FDX2 Sarah Leigh Source NHS GMS was added to FDX2.
Source Expert Review Green was added to FDX2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v1.293 DNM2 Sarah Leigh Source NHS GMS was added to DNM2.
Source Expert Review Green was added to DNM2.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Mitochondrial disorders v1.293 COQ7 Sarah Leigh Source NHS GMS was added to COQ7.
Source Expert Review Green was added to COQ7.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Mitochondrial disorders v1.293 COA7 Sarah Leigh gene: COA7 was added
gene: COA7 was added to Mitochondrial disorders. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: COA7 was set to
Mitochondrial disorders v1.293 COA6 Sarah Leigh Source NHS GMS was added to COA6.
Source Expert Review Green was added to COA6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v1.293 CA5A Sarah Leigh gene: CA5A was added
gene: CA5A was added to Mitochondrial disorders. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: CA5A was set to
Mitochondrial disorders v1.293 C19orf70 Sarah Leigh gene: C19orf70 was added
gene: C19orf70 was added to Mitochondrial disorders. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: C19orf70 was set to
Mitochondrial disorders v1.293 ATP5D Sarah Leigh gene: ATP5D was added
gene: ATP5D was added to Mitochondrial disorders. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: ATP5D was set to
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.114 SHOC2 Eleanor Williams Classified gene: SHOC2 as Amber List (moderate evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.114 SHOC2 Eleanor Williams Added comment: Comment on list classification: Upgrading from red to amber. Amber rating agreed at the GMS musculoskeletal specialist test group Webex on 2019-05-13. A Noonan syndrome-related gene, but the group decided it should be Amber as there is a less well-evidenced association.
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.114 SHOC2 Eleanor Williams Gene: shoc2 has been classified as Amber List (Moderate Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.113 IFT122 Eleanor Williams Classified gene: IFT122 as Green List (high evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.113 IFT122 Eleanor Williams Added comment: Comment on list classification: Upgrading from red to green. Green rating agreed at the GMS musculoskeletal specialist test group Webex on 2019-05-13. 3 cases now reported.
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.113 IFT122 Eleanor Williams Gene: ift122 has been classified as Green List (High Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.112 SEC24D Eleanor Williams Phenotypes for gene: SEC24D were changed from Cole-Carpenter syndrome 2 to Cole-Carpenter syndrome 2 616294
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.111 SEC24D Eleanor Williams Publications for gene: SEC24D were set to 25683121
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.110 SEC24D Eleanor Williams Mode of inheritance for gene: SEC24D was changed from to BIALLELIC, autosomal or pseudoautosomal
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.109 SEC24D Eleanor Williams Classified gene: SEC24D as Amber List (moderate evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.109 SEC24D Eleanor Williams Added comment: Comment on list classification: Upgrading to Amber as there are 3 potentially relevant cases associated with variants in SEC24D. Waiting for the GMS musculoskeletal specialist test group to confirm whether all cases are relevant and it should be upgraded to green or not.
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.109 SEC24D Eleanor Williams Gene: sec24d has been classified as Amber List (Moderate Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.108 SPECC1L Eleanor Williams Phenotypes for gene: SPECC1L were changed from Opitz G/BBB syndrome type 2 to Opitz GBBB syndrome, type II 145410
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.107 SPECC1L Eleanor Williams Classified gene: SPECC1L as Green List (high evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.107 SPECC1L Eleanor Williams Added comment: Comment on list classification: Upgrading from red to green. Green rating agreed at the GMS musculoskeletal specialist test group Webex on 2019-05-13.
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.107 SPECC1L Eleanor Williams Gene: specc1l has been classified as Green List (High Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.106 HUWE1 Eleanor Williams commented on gene: HUWE1: NOTE: Variants in a specific codon (R110) associated with craniosynostosis. Variants in other codons are associated with intellectual disability.
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.106 HUWE1 Eleanor Williams Publications for gene: HUWE1 were set to 25985138; 25590979:29180823
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.105 HUWE1 Eleanor Williams Mode of inheritance for gene: HUWE1 was changed from to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.104 HUWE1 Eleanor Williams Classified gene: HUWE1 as Green List (high evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.104 HUWE1 Eleanor Williams Added comment: Comment on list classification: Upgrading from red to green. Green rating agreed at the GMS musculoskeletal specialist test group Webex on 2019-05-13.
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.104 HUWE1 Eleanor Williams Gene: huwe1 has been classified as Green List (High Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.103 GNAS Eleanor Williams Classified gene: GNAS as Green List (high evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.103 GNAS Eleanor Williams Added comment: Comment on list classification: Upgrading from red to green. Green rating agreed at the GMS musculoskeletal specialist test group Webex on 2019-05-13. Andrew Wilkie of Wessex and West Midlands GLH confirmed unpublished cases.
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.103 GNAS Eleanor Williams Gene: gnas has been classified as Green List (High Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.102 GNAS Eleanor Williams Deleted their comment
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.102 GNAS Eleanor Williams Publications for gene: GNAS were set to 19530187; 26340332
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.101 GNAS Eleanor Williams Added comment: Comment on publications: Graul-Neumann et al 2009 - PMID: 19530187
Twigg et al 2015 - PMID: 26340332
Adetayo et al 2015 - PMID: 26267576
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.101 GNAS Eleanor Williams Publications for gene: GNAS were set to 19530187; 26340332
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.100 GNAS Eleanor Williams Classified gene: GNAS as Red List (low evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.100 GNAS Eleanor Williams Added comment: Comment on list classification: Upgrading from red to green. Green rating agreed at the GMS musculoskeletal specialist test group Webex on 2019-05-13. Andrew Wilkie of Wessex and West Midlands GLH confirmed several unpublished cases.
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.100 GNAS Eleanor Williams Gene: gnas has been classified as Red List (Low Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.99 FAM20C Eleanor Williams Phenotypes for gene: FAM20C were changed from Raine syndrome to Raine syndrome 259775
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.98 FAM20C Eleanor Williams Mode of inheritance for gene: FAM20C was changed from to BIALLELIC, autosomal or pseudoautosomal
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.97 FAM20C Eleanor Williams Classified gene: FAM20C as Green List (high evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.97 FAM20C Eleanor Williams Added comment: Comment on list classification: Upgrading from red to green. Green rating agreed at the GMS musculoskeletal specialist test group Webex on 2019-05-13. Andrew Wilkie of Wessex and West Midlands GLH confirmed several unpublished cases.
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.97 FAM20C Eleanor Williams Gene: fam20c has been classified as Green List (High Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.96 CYP26B1 Eleanor Williams Mode of inheritance for gene: CYP26B1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.95 CYP26B1 Eleanor Williams Classified gene: CYP26B1 as Green List (high evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.95 CYP26B1 Eleanor Williams Added comment: Comment on list classification: Upgrading from red to green. Green rating agreed at the GMS musculoskeletal specialist test group Webex on 2019-05-13. Now 3 cases
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.95 CYP26B1 Eleanor Williams Gene: cyp26b1 has been classified as Green List (High Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.94 SLC25A24 Eleanor Williams Classified gene: SLC25A24 as Green List (high evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.94 SLC25A24 Eleanor Williams Added comment: Comment on list classification: Upgrading from red to green. Green rating agreed at the GMS musculoskeletal specialist test group Webex on 2019-05-13. . > 3 cases but same variant in 4 cases and same codon in all, likely because activating mutation rather than founder effect.
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.94 SLC25A24 Eleanor Williams Gene: slc25a24 has been classified as Green List (High Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.93 SLC25A24 Eleanor Williams Mode of inheritance for gene: SLC25A24 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.92 P4HB Eleanor Williams Classified gene: P4HB as Green List (high evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.92 P4HB Eleanor Williams Added comment: Comment on list classification: Upgrading from red to green. Green rating agreed at the GMS musculoskeletal specialist test group Webex on 2019-05-13.
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.92 P4HB Eleanor Williams Gene: p4hb has been classified as Green List (High Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.91 P4HB Eleanor Williams Phenotypes for gene: P4HB were changed from Cole-Carpenter syndrome 1 to Cole-Carpenter syndrome 1 112240
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.90 P4HB Eleanor Williams Mode of inheritance for gene: P4HB was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.89 ARSB Eleanor Williams Classified gene: ARSB as Green List (high evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.89 ARSB Eleanor Williams Added comment: Comment on list classification: Upgrading from red to green. Green rating agreed at the GMS musculoskeletal specialist test group Webex on 2019-05-13.
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.89 ARSB Eleanor Williams Gene: arsb has been classified as Green List (High Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.88 ARSB Eleanor Williams Mode of inheritance for gene: ARSB was changed from to BIALLELIC, autosomal or pseudoautosomal
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.87 JAG1 Eleanor Williams Classified gene: JAG1 as Green List (high evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.87 JAG1 Eleanor Williams Added comment: Comment on list classification: Upgrading from red to green. Green rating agreed at the GMS musculoskeletal specialist test group Webex on 2019-05-13.