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Cytopenias and congenital anaemias v1.100 KLF1 Arina Puzriakova Mode of inheritance for gene: KLF1 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
Cytopenias and congenital anaemias v1.99 KLF1 Arina Puzriakova Publications for gene: KLF1 were set to 21055716
Cytopenias and congenital anaemias v1.98 KLF1 Arina Puzriakova Phenotypes for gene: KLF1 were changed from Congenital Dyserythropoietic Anemia; Dyserythropoietic anemia, congenital, type IV, 613673 to Dyserythropoietic anemia, congenital, type IV, OMIM:613673
Cytopenia - NOT Fanconi anaemia v1.55 KLF1 Arina Puzriakova Tag Q1_22_MOI tag was added to gene: KLF1.
Rare anaemia v1.36 KLF1 Arina Puzriakova Tag Q1_22_MOI tag was added to gene: KLF1.
Cytopenia - NOT Fanconi anaemia v1.55 KLF1 Arina Puzriakova Added comment: Comment on mode of inheritance: MOI should be updated from 'Monoallelic' only to 'Both mono- and biallelic, (biallelic more severe)'.

The expanded MOI is based on compound heterozygous cases in PMID:24443441; 25724378; 27282573; 28361594; 28369821. Heterozygous carrier parents may display features of beta thalassemia.
Cytopenia - NOT Fanconi anaemia v1.55 KLF1 Arina Puzriakova Mode of inheritance for gene: KLF1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Cytopenia - NOT Fanconi anaemia v1.54 KLF1 Arina Puzriakova Publications for gene: KLF1 were set to 21055716
Cytopenia - NOT Fanconi anaemia v1.53 KLF1 Arina Puzriakova Phenotypes for gene: KLF1 were changed from Dyserythropoietic anemia, congenital, type IV, 613673; Congenital Dyserythropoietic Anemia to Dyserythropoietic anemia, congenital, type IV, OMIM:613673
Rare anaemia v1.36 KLF1 Arina Puzriakova Phenotypes for gene: KLF1 were changed from Dyserythropoietic anemia, congenital, type IV, 613673; Dyserythropoietic anemia, congenital, type IV; Congenital Dyserythropoietic Anemia; 613673 Congenital Dyserythropoietic Anemia; 613673 Congenital dyserythropoietic anaemia type 4 to Dyserythropoietic anemia, congenital, type IV, OMIM:613673
Rare anaemia v1.35 KLF1 Arina Puzriakova Publications for gene: KLF1 were set to 21055716; 29200155
Rare anaemia v1.34 KLF1 Arina Puzriakova Added comment: Comment on mode of inheritance: MOI should be updated from 'Monoallelic' only to 'Both mono- and biallelic, (biallelic more severe)'.

The expanded MOI is based on compound heterozygous cases in PMID:24443441; 25724378; 27282573; 28361594; 28369821. Heterozygous carrier parents may display features of beta thalassemia.
Rare anaemia v1.34 KLF1 Arina Puzriakova Mode of inheritance for gene: KLF1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Cytopenias and congenital anaemias v1.97 KIT Arina Puzriakova Phenotypes for gene: KIT were changed from Acute myeloid leukaemia (AML) to Leukemia, acute myeloid, somatic, OMIM:601626
Adult solid tumours cancer susceptibility v2.15 KIT Arina Puzriakova Phenotypes for gene: KIT were changed from Gastro-Intestinal Stromal Tumor to Gastrointestinal stromal tumor, familial, OMIM:606764
Sarcoma cancer susceptibility v1.21 KIT Arina Puzriakova Phenotypes for gene: KIT were changed from to Gastrointestinal stromal tumor, familial, OMIM:606764
Adult solid tumours for rare disease v1.26 KIT Arina Puzriakova Phenotypes for gene: KIT were changed from Gastro-Intestinal Stromal Tumor to Gastrointestinal stromal tumor, familial, OMIM:606764
Pigmentary skin disorders v1.40 KIT Arina Puzriakova Tag Q1_22_MOI tag was added to gene: KIT.
Pigmentary skin disorders v1.40 KIT Arina Puzriakova Publications for gene: KIT were set to 9990072; 1370874
Pigmentary skin disorders v1.39 KIT Arina Puzriakova Phenotypes for gene: KIT were changed from PBT; Piebaldism; MASTC, PIEBALD TRAIT; Mast cell disease; MASTOCYTOSIS, CUTANEOUS to Mastocytosis, cutaneous, OMIM:154800; Piebaldism, OMIM:172800
Pigmentary skin disorders v1.38 KIT Arina Puzriakova Added comment: Comment on mode of inheritance: MOI should be be updated from 'monoallelic' to 'both mono- and biallelic (but biallelic mutations cause a more SEVERE disease form)' (tagged)

Copied from Ellen McDonagh (Genomics England Curator) review on Hearing loss panel:
PMID: 23399981 - A report of a proband with no pigmentation of his skin nor hair and blue irides, and pro- found sensorineural hearing loss. A homozygous deletion of exons 20 and 21 in the proband was found, and parents were heterozygous for these deletions (homozygosity for piebaldism is clinically more severe than heterozygous state). Also describe other published studies of c-kit mutations in mice, which have defects including albinism and deafness.
Pigmentary skin disorders v1.38 KIT Arina Puzriakova Mode of inheritance for gene: KIT was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare genetic inflammatory skin disorders v1.50 KIT Arina Puzriakova Phenotypes for gene: KIT were changed from MASTOCYTOSIS, CUTANEOUS, OMIM:154800; Piebaldism, OMIM:172800 to Mastocytosis, cutaneous, OMIM:154800
Neonatal diabetes v2.35 KCNJ11 Ivone Leong Tag Q1_22_MOI tag was added to gene: KCNJ11.
Neonatal diabetes v2.35 KCNJ11 Ivone Leong edited their review of gene: KCNJ11: Added comment: MOI should be changed from "BOTH monoallelic and biallelic, autosomal or pseudoautosomal" to "Monoallelic" as neonatal diabetes is associated with monoallelic inheritance. Both monoallelic and biallelic inheritance is associated with familial hyperinsulinemic hypoglycaemia.; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Monogenic hearing loss v2.218 ADGRV1 Ivone Leong Tag Q1_22_MOI tag was added to gene: ADGRV1.
Monogenic hearing loss v2.218 ADGRV1 Ivone Leong reviewed gene: ADGRV1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Familial pulmonary fibrosis v1.26 ACD Ivone Leong Tag watchlist tag was added to gene: ACD.
Familial pulmonary fibrosis v1.26 ACD Ivone Leong Publications for gene: ACD were set to 31515401; 30995915
Familial pulmonary fibrosis v1.25 ACD Ivone Leong Classified gene: ACD as Amber List (moderate evidence)
Familial pulmonary fibrosis v1.25 ACD Ivone Leong Added comment: Comment on list classification: New gene added by Øystein Holla (Telemark Hospital Trust). This gene is associated with a phenotype in OMIM but not in Gene2Phenotype. After discussion with the Genomics England Clinical Team this gene has been given an Amber rating until more evidence is available due to unaffected heterozygotes reported in PMID: 33446513.
Familial pulmonary fibrosis v1.25 ACD Ivone Leong Gene: acd has been classified as Amber List (Moderate Evidence).
Familial pulmonary fibrosis v1.24 ACD Ivone Leong Phenotypes for gene: ACD were changed from dyskeratosis congenita, telomere disorder, pulmonary fibrosis to ?Dyskeratosis congenita, autosomal dominant 6, OMIM:616553; ?Dyskeratosis congenita, autosomal recessive 7, OMIM:616553
Familial pulmonary fibrosis v1.23 ACD Ivone Leong Publications for gene: ACD were set to 31515401
Early onset or syndromic epilepsy v2.489 CHKA Konstantinos Varvagiannis gene: CHKA was added
gene: CHKA was added to Genetic epilepsy syndromes. Sources: Literature
Mode of inheritance for gene: CHKA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHKA were set to 35202461
Phenotypes for gene: CHKA were set to Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature
Penetrance for gene: CHKA were set to Complete
Review for gene: CHKA was set to GREEN
Added comment: Klöckner (2022 - PMID: 35202461) describe the phenotype of 6 individuals (from 5 unrelated families) harboring biallelic CHKA variants.

Shared features incl. abnormal muscle tone(6/6 - hypertonia or hypotonia, 3/6 each), DD/ID (6/6,severe in 4, severe/profound in 2), epilepsy (6/6 - onset: infancy - 3y2m | epileptic spasms or GS at onset), microcephaly (6/6), movement disorders (3/6 - incl. dyskinesia, rigidity, choreoatetotic movements). 2/5 individuals exhibited MRI abnormalities, notably hypomyelination. Short stature was observed in 4/6.

Eventual previous genetic testing was not discussed.

Exome sequencing (quattro ES for 2 sibs, trio ES for 1 individual, singleton for 3 probands) revealed biallelic CHKA variants in all affected individuals. Sanger sequencing was performed for confirmation and segregation studies.

Other variants (in suppl.) were not deemed to be causative for the neurodevelopmental phenotype.

3 different missense, 1 start-loss and 1 truncating variant were identified, namely (NM_0012772.2):
- c.421C>T/p.(Arg141Trp) [3 hmz subjects from 2 consanguineous families],
- c.580C>T/p.Pro194Ser [1 hmz individual born to consanguineous parents],
- c.2T>C/p.(Met1?) [1 hmz individual born to related parents],
- c.14dup/p.(Cys6Leufs*19) in trans with c.1021T>C/p.(Phe341Leu) in 1 individual.

CHKA encodes choline kinase alpha, an enzyme catalyzing the first step of phospholipid synthesis in the Kennedy pathway. The pathway is involved in de novo synthesis of glycerophospholipids, phosphatidylcholine and phosphatidylethanolamine being the most abundant in eukaryotic membranes.

CHKA with its paralog (CHKB) phosphorylates either choline or ethanolamine to phosphocholine or phosphoethanolamine respectively with conversion of ATP to ADP.

As the authors comment, biallelic pathogenic variants in CHKB cause a NDD with muscular dystrophy, hypotonia, ID, microcephaly and structural mitochondrial anomalies (MIM 602541). [Prominent mitochondrial patterning was observed in a single muscle biopsy available from an individual with biallelic CHKA variants].

Other disorders of the Kennedy pathway (due to biallelic PCYT2, SELENOI, PCYT1A variants) present with overlapping features incl. variable DD/ID (no-severe), microcephaly, seizures, visual impairment etc.

CHKA variants were either absent or observed once in gnomAD, affected highly conserved AAs with multiple in silico predictions in favor of a deleterious effect.

In silico modeling suggests structural effects for several of the missense variants (Arg141Trp, Pro194Ser presumably affect ADP binding, Phe341 lying close to the binding site of phosphocholine).

Each of the missense variants was expressed in yeast cells and W. Blot suggested expression at the expected molecular weight at comparative levels. The 3 aforementioned variants exhibited reduced catalytic activity (20%, 15%, 50% respectively).

NMD is thought to underly the deleterious effect of the frameshift one (not studied).

The start-loss variant is expected to result in significantly impaired expression and protein function as eventual utilization of the next possible start codon - occurring at position 123 - would remove 26% of the protein.

Chka(-/-) is embryonically lethal in mice, suggesting that complete loss is not compatible with life. Reduction of choline kinase activity by 30% in heterozygous mice did not appear to result in behavioral abnormalities although this was not studied in detail (PMID cited: 18029352). Finally, screening of 1566 mouse lines identified 198 genes whose disruption yields neuroanatomical phenotypes, Chka(+/-) mice being among these (PMID cited: 31371714).

There is no associated phenotype in OMIM, Gene2Phenotype or SysID.

Overall this gene can be considered for inclusion in the ID and epilepsy panes with green or amber rating (>3 individuals, >3 variants, variant studies, overlapping phenotype of disorders belonging to the same pathway, etc). Consider also inclusion in the microcephaly panel (where available this seemed to be of postnatal onset).
Sources: Literature
Intellectual disability v3.1500 CHKA Konstantinos Varvagiannis gene: CHKA was added
gene: CHKA was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: CHKA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHKA were set to 35202461
Phenotypes for gene: CHKA were set to Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature
Penetrance for gene: CHKA were set to Complete
Review for gene: CHKA was set to GREEN
Added comment: Klöckner (2022 - PMID: 35202461) describe the phenotype of 6 individuals (from 5 unrelated families) harboring biallelic CHKA variants.

Shared features incl. abnormal muscle tone(6/6 - hypertonia or hypotonia, 3/6 each), DD/ID (6/6,severe in 4, severe/profound in 2), epilepsy (6/6 - onset: infancy - 3y2m | epileptic spasms or GS at onset), microcephaly (6/6), movement disorders (3/6 - incl. dyskinesia, rigidity, choreoatetotic movements). 2/5 individuals exhibited MRI abnormalities, notably hypomyelination. Short stature was observed in 4/6.

Eventual previous genetic testing was not discussed.

Exome sequencing (quattro ES for 2 sibs, trio ES for 1 individual, singleton for 3 probands) revealed biallelic CHKA variants in all affected individuals. Sanger sequencing was performed for confirmation and segregation studies.

Other variants (in suppl.) were not deemed to be causative for the neurodevelopmental phenotype.

3 different missense, 1 start-loss and 1 truncating variant were identified, namely (NM_0012772.2):
- c.421C>T/p.(Arg141Trp) [3 hmz subjects from 2 consanguineous families],
- c.580C>T/p.Pro194Ser [1 hmz individual born to consanguineous parents],
- c.2T>C/p.(Met1?) [1 hmz individual born to related parents],
- c.14dup/p.(Cys6Leufs*19) in trans with c.1021T>C/p.(Phe341Leu) in 1 individual.

CHKA encodes choline kinase alpha, an enzyme catalyzing the first step of phospholipid synthesis in the Kennedy pathway. The pathway is involved in de novo synthesis of glycerophospholipids, phosphatidylcholine and phosphatidylethanolamine being the most abundant in eukaryotic membranes.

CHKA with its paralog (CHKB) phosphorylates either choline or ethanolamine to phosphocholine or phosphoethanolamine respectively with conversion of ATP to ADP.

As the authors comment, biallelic pathogenic variants in CHKB cause a NDD with muscular dystrophy, hypotonia, ID, microcephaly and structural mitochondrial anomalies (MIM 602541). [Prominent mitochondrial patterning was observed in a single muscle biopsy available from an individual with biallelic CHKA variants].

Other disorders of the Kennedy pathway (due to biallelic PCYT2, SELENOI, PCYT1A variants) present with overlapping features incl. variable DD/ID (no-severe), microcephaly, seizures, visual impairment etc.

CHKA variants were either absent or observed once in gnomAD, affected highly conserved AAs with multiple in silico predictions in favor of a deleterious effect.

In silico modeling suggests structural effects for several of the missense variants (Arg141Trp, Pro194Ser presumably affect ADP binding, Phe341 lying close to the binding site of phosphocholine).

Each of the missense variants was expressed in yeast cells and W. Blot suggested expression at the expected molecular weight at comparative levels. The 3 aforementioned variants exhibited reduced catalytic activity (20%, 15%, 50% respectively).

NMD is thought to underly the deleterious effect of the frameshift one (not studied).

The start-loss variant is expected to result in significantly impaired expression and protein function as eventual utilization of the next possible start codon - occurring at position 123 - would remove 26% of the protein.

Chka(-/-) is embryonically lethal in mice, suggesting that complete loss is not compatible with life. Reduction of choline kinase activity by 30% in heterozygous mice did not appear to result in behavioral abnormalities although this was not studied in detail (PMID cited: 18029352). Finally, screening of 1566 mouse lines identified 198 genes whose disruption yields neuroanatomical phenotypes, Chka(+/-) mice being among these (PMID cited: 31371714).

There is no associated phenotype in OMIM, Gene2Phenotype or SysID.

Overall this gene can be considered for inclusion in the ID and epilepsy panes with green or amber rating (>3 individuals, >3 variants, variant studies, overlapping phenotype of disorders belonging to the same pathway, etc). Consider also inclusion in the microcephaly panel (where available this seemed to be of postnatal onset).
Sources: Literature
Osteopetrosis v1.27 RASGRP2 Zornitza Stark reviewed gene: RASGRP2: Rating: RED; Mode of pathogenicity: None; Publications: 18709451; Phenotypes: Bleeding disorder, platelet-type, 18 - MIM#615888, Osteopetrosis (disease) MONDO:0017198; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Familial hypercholesterolaemia (GMS) v1.10 APOE Sarah Leigh Tag Q1_22_MOI tag was added to gene: APOE.
Familial hypercholesterolaemia v1.29 APOE Sarah Leigh Tag Q1_22_MOI tag was added to gene: APOE.
Familial hypercholesterolaemia v1.29 APOE Sarah Leigh Publications for gene: APOE were set to 23433584; 22949395; 26802169; 11095479; 16094309; 22481068; 24267230
Familial hypercholesterolaemia v1.28 APOE Sarah Leigh edited their review of gene: APOE: Added comment: PMID: 34058468, reviews APOE variants found in primary dyslipidemia. Table 1 lists both monoallelic and biallelic APOE variants associated with hypercholesterolemia.; Changed rating: GREEN; Changed publications to: 34058468; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Familial hypercholesterolaemia (GMS) v1.10 APOE Sarah Leigh edited their review of gene: APOE: Added comment: PMID: 34058468, reviews APOE variants found in primary dyslipidemia. Table 1 lists both monoallelic and biallelic APOE variants associated with hypercholesterolemia.; Changed rating: GREEN; Changed publications to: 34058468; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Familial hypercholesterolaemia (GMS) v1.10 APOE Sarah Leigh Publications for gene: APOE were set to 11095479; 23433584; 24267230; 26802169; 16094309; 22481068; 22949395
Pulmonary fibrosis familial v0.4 MUC5B Arina Puzriakova commented on gene: MUC5B: This gene has been added to the panel on the recommendation of the NHS Genomic Medicine Service and should be rated green.
Pulmonary fibrosis familial v0.4 MUC5B Arina Puzriakova Classified gene: MUC5B as Green List (high evidence)
Pulmonary fibrosis familial v0.4 MUC5B Arina Puzriakova Gene: muc5b has been classified as Green List (High Evidence).
Pulmonary fibrosis familial v0.3 MUC5B Arina Puzriakova Publications for gene: MUC5B were set to 21506748; 21506741
Pulmonary fibrosis familial v0.2 MUC5B Arina Puzriakova changed review comment from: Single common SNP in the promoter of MUC5B confers susceptibility to idiopathic pulmonary fibrosis.

Applicant review states, 'There are no known or published ethnic differences in detection rates, except for a low allele frequency of a MUC5B promotor SNP in Africans, which is known to be a risk allele for FPF. This SNP would be included in a gene panel for FPF'; to: Association of the minor allele (T) of a single common SNP in the promoter of MUC5B (rs35705950), conferring susceptibility to idiopathic pulmonary fibrosis.

Applicant review states, 'There are no known or published ethnic differences in detection rates, except for a low allele frequency of a MUC5B promotor SNP in Africans, which is known to be a risk allele for FPF. This SNP would be included in a gene panel for FPF'
Ectodermal dysplasia v1.33 HR Arina Puzriakova Publications for gene: HR were set to
Non-syndromic hypotrichosis v1.11 HR Arina Puzriakova Phenotypes for gene: HR were changed from Hypotrichosis 4, 146550; HYPT4; Marie Unna hereditary hypotrichosis 1 (MUHH1); Marie Unna hereditary hypotrichosis (MUHH) to Marie Unna hereditary hypotrichosis (MUHH); Alopecia universalis, OMIM:203655
Ectodermal dysplasia v1.32 HR Arina Puzriakova Phenotypes for gene: HR were changed from HYPT4; Marie Unna hereditary hypotrichosis 1 (MUHH1); Marie Unna hereditary hypotrichosis (MUHH); Hypotrichosis 4, 146550 to Marie Unna hereditary hypotrichosis (MUHH); Alopecia universalis, OMIM:203655; Atrichia with papular lesions, OMIM:209500
Ectodermal dysplasia v1.31 HR Arina Puzriakova Tag Q1_22_MOI tag was added to gene: HR.
Ectodermal dysplasia v1.31 HR Arina Puzriakova Added comment: Comment on mode of inheritance: MOI should be updated from 'monoallelic' to 'both mono- and biallelic'. Heterozygous variants in the 5'UTR of HR have been shown to cause Marie Unna hereditary hypotrichosis while homozygous variants have been associated with Alopecia universalis (MIM# 203655) and Atrichia with papular lesions (MIM# 209500), therefore both inheritance patterns are relevant to this panel.
Ectodermal dysplasia v1.31 HR Arina Puzriakova Mode of inheritance for gene: HR was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Non-syndromic hypotrichosis v1.10 HR Arina Puzriakova Added comment: Comment on mode of inheritance: Updated MOI from 'monoallelic' to 'both mono- and biallelic'. Heterozygous variants in the 5'UTR of HR have been shown to cause Marie Unna hereditary hypotrichosis while homozygous variants have been associated with Alopecia universalis (MIM# 203655) and Atrichia with papular lesions (MIM# 209500), therefore both inheritance patterns are relevant to this panel.
Non-syndromic hypotrichosis v1.10 HR Arina Puzriakova Mode of inheritance for gene: HR was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v1.104 HARS Arina Puzriakova Mode of inheritance for gene: HARS was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Additional findings health related v0.112 CFTR Arina Puzriakova Mode of inheritance for gene: CFTR was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Additional findings health related v0.111 CFTR Arina Puzriakova Mode of inheritance for gene: CFTR was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal
Primary ovarian insufficiency v1.64 YTHDC2 Ivone Leong Added comment: Comment on publications: Added new publication submitted by Andrey Gagunashvili. PMID:35138268
Primary ovarian insufficiency v1.64 YTHDC2 Ivone Leong Publications for gene: YTHDC2 were set to 29033321; 29360036
Primary immunodeficiency or monogenic inflammatory bowel disease v2.527 DCLRE1B Arina Puzriakova commented on gene: DCLRE1B: Added 'to_be_confirmed_NHSE' tag as demotion of this gene requires further discussion
Primary immunodeficiency or monogenic inflammatory bowel disease v2.527 DCLRE1B Arina Puzriakova Tag to_be_confirmed_NHSE tag was added to gene: DCLRE1B.
Optic neuropathy v2.56 ACO2 Tom Cullup edited their review of gene: ACO2: Added comment: New paper (34056600) describing ACO2 as a cause of autosomal dominant optic atrophy - update of inheritance needed.; Changed publications to: 25351951, 22405087, 34056600; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Set current diagnostic: yes
Multi locus imprinting disorders v0.13 Sarah Leigh List of related panels changed from to R417
Multi locus imprinting disorders v0.12 PLAGL1 Sarah Leigh Classified gene: PLAGL1 as Amber List (moderate evidence)
Multi locus imprinting disorders v0.12 PLAGL1 Sarah Leigh Added comment: Comment on list classification: This gene has been demoted to Amber as it is not appropriate for the NHS clinical indication R417 Multi locus imprinting disorders (https://www.england.nhs.uk/publication/national-genomic-test-directories).
Multi locus imprinting disorders v0.12 PLAGL1 Sarah Leigh Gene: plagl1 has been classified as Amber List (Moderate Evidence).
Multi locus imprinting disorders v0.11 GRB10 Sarah Leigh Classified gene: GRB10 as Amber List (moderate evidence)
Multi locus imprinting disorders v0.11 GRB10 Sarah Leigh Added comment: Comment on list classification: This gene has been demoted to Amber as it is not appropriate for the NHS clinical indication R417 Multi locus imprinting disorders (https://www.england.nhs.uk/publication/national-genomic-test-directories).
Multi locus imprinting disorders v0.11 GRB10 Sarah Leigh Gene: grb10 has been classified as Amber List (Moderate Evidence).
Multi locus imprinting disorders v0.10 KHDC3L Sarah Leigh Entity copied from Genomic imprinting v0.138
Multi locus imprinting disorders v0.10 KHDC3L Sarah Leigh gene: KHDC3L was added
gene: KHDC3L was added to Multi locus imprinting disorders. Sources: Imprinting GeCIP Subdomain,Expert Review Green
Mode of inheritance for gene: KHDC3L was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: KHDC3L were set to 21885028; 23232697; 31847873; 31201414
Phenotypes for gene: KHDC3L were set to Hydatidiform mole, recurrent, 2 OMIM:614293; hydatidiform mole, recurrent, 2 MONDO:0013671
Penetrance for gene: KHDC3L were set to Complete
Multi locus imprinting disorders v0.9 PADI6 Sarah Leigh Entity copied from Genomic imprinting v0.138
Multi locus imprinting disorders v0.9 PADI6 Sarah Leigh gene: PADI6 was added
gene: PADI6 was added to Multi locus imprinting disorders. Sources: Literature,Expert Review Green
Mode of inheritance for gene: PADI6 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: PADI6 were set to 32928291; 33221824; 27545678
Phenotypes for gene: PADI6 were set to Preimplantation embryonic lethality 2 OMIM:617234; preimplantation embryonic lethality 2 MONDO:0014978; Beckwith-Wiedemann syndrome; Multi Locus Imprinting Disturbance
Multi locus imprinting disorders v0.8 NLRP7 Sarah Leigh Entity copied from Genomic imprinting v0.138
Multi locus imprinting disorders v0.8 NLRP7 Sarah Leigh gene: NLRP7 was added
gene: NLRP7 was added to Multi locus imprinting disorders. Sources: Imprinting GeCIP Subdomain,Expert Review Green
Mode of inheritance for gene: NLRP7 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: NLRP7 were set to 16462743; 19246479; 31201414; 29574422; 28916717
Phenotypes for gene: NLRP7 were set to Phenotype resulting from under expression: Biparental complete hydatidiform mole; Affected tissue: all (incompatible with life); Multi Locus Imprinting Disturbance; hydatidiform mole, recurrent, 1 MONDO:0009273
Penetrance for gene: NLRP7 were set to Complete
Multi locus imprinting disorders v0.7 NLRP5 Sarah Leigh Entity copied from Genomic imprinting v0.138
Multi locus imprinting disorders v0.7 NLRP5 Sarah Leigh gene: NLRP5 was added
gene: NLRP5 was added to Multi locus imprinting disorders. Sources: Imprinting GeCIP Subdomain,Expert Review Green
Mode of inheritance for gene: NLRP5 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: NLRP5 were set to 26323243; 31201414; 31829238
Phenotypes for gene: NLRP5 were set to Phenotype resulting from under expression: Biparental complete hydatidiform mole, Beckwith-Wiedemann Syndrome, Multi-locus imprinting disorder; Affected tissue: all
Penetrance for gene: NLRP5 were set to Complete
Multi locus imprinting disorders v0.6 NLRP2 Sarah Leigh Entity copied from Genomic imprinting v0.137
Multi locus imprinting disorders v0.6 NLRP2 Sarah Leigh gene: NLRP2 was added
gene: NLRP2 was added to Multi locus imprinting disorders. Sources: Imprinting GeCIP Subdomain,Expert Review Green
watchlist tags were added to gene: NLRP2.
Mode of inheritance for gene: NLRP2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: NLRP2 were set to 19300480; 30221575; 32169557; 28422141; 28317850; 26323243; 29574422; 30877238; 33090377
Phenotypes for gene: NLRP2 were set to Beckwith-Wiedemann syndrome due to imprinting defect of 11p15 MONDO:0016475
Penetrance for gene: NLRP2 were set to Complete
Mode of pathogenicity for gene: NLRP2 was set to Other
Rare multisystem ciliopathy disorders v1.158 XPNPEP3 Sarah Leigh Classified gene: XPNPEP3 as Green List (high evidence)
Rare multisystem ciliopathy disorders v1.158 XPNPEP3 Sarah Leigh Gene: xpnpep3 has been classified as Green List (High Evidence).
Rare multisystem ciliopathy disorders v1.157 XPNPEP3 Sarah Leigh edited their review of gene: XPNPEP3: Added comment: Associated with relevant phenotype in OMIM and as limited Gen2Phen gene. At least three variants were reported in three unrelated cases (PMID: 32660933; 20179356). Two of the variants were terminating (RCV000000069, RCV001554332) and the third was a missense variant (RCV000000068), that seems to activate a cryptic splice site; RT-PCR of lymphoblastoid cells showed that this resulted in the inclusion of intronic bases and a frameshift. Cilia-related function was examined by the suppression of zebrafish xpnpep3, resulting in phenotypes reminiscent of ciliopathy morphants, this effect was rescued by human XPNPEP3 that was devoid of a mitochondrial localization signal (PMID: 20179356).
Feedback from Helen Brittain (GEL Clinical Fellow): this gene is suitable for this panel.; Changed rating: GREEN
Pulmonary fibrosis familial v0.2 MUC5B Arina Puzriakova Tag promoter tag was added to gene: MUC5B.
Pulmonary fibrosis familial v0.2 ZCCHC8 Arina Puzriakova changed review comment from: This gene has been confirmed for this panel by the NHS Genomic Medicine Service and should be rated green. Applicant review states, The Clinical Genetics and Genomics Laboratory, RBHT has been delivering this testing as a pilot study for in-house patients for the past 2 years. Testing has been as part of a large inherited respiratory conditions gene panel, with SNV and CNV analysis.; to: This gene has been confirmed for this panel by the NHS Genomic Medicine Service and should be rated green.

Applicant review states, 'The Clinical Genetics and Genomics Laboratory, RBHT has been delivering this testing as a pilot study for in-house patients for the past 2 years. Testing has been as part of a large inherited respiratory conditions gene panel, with SNV and CNV analysis.'
Pulmonary fibrosis familial v0.2 MUC5B Arina Puzriakova changed review comment from: Single common SNP in the promoter of MUC5B confers susceptibility to idiopathic pulmonary fibrosis. Applicant review states, 'There are no known or published ethnic differences in detection rates, except for a low allele frequency of a MUC5B promotor SNP in Africans, which is known to be a risk allele for FPF. This SNP would be included in a gene panel for FPF'; to: Single common SNP in the promoter of MUC5B confers susceptibility to idiopathic pulmonary fibrosis.

Applicant review states, 'There are no known or published ethnic differences in detection rates, except for a low allele frequency of a MUC5B promotor SNP in Africans, which is known to be a risk allele for FPF. This SNP would be included in a gene panel for FPF'
Pulmonary fibrosis familial v0.2 RTEL1 Arina Puzriakova changed review comment from: This gene has been added to the panel on the recommendation of the NHS Genomic Medicine Service and should be rated green. Applicant review states, There is extensive phenotypic and genotypic overlap with other telomeropathies, such as dyskeratosis congenita and Hermansky-Pudlak Syndrome, all of which have pulmonary fibrosis as a clinical feature. Some of the genes included in the panel have an autosomal recessive inheritance pattern in those disorders, but individuals who are heterozygous for pathogenic variants in the genes may develop later-onset pulmonary fibrosis.; to: This gene has been added to the panel on the recommendation of the NHS Genomic Medicine Service and should be rated green.

Applicant review states, 'There is extensive phenotypic and genotypic overlap with other telomeropathies, such as dyskeratosis congenita and Hermansky-Pudlak Syndrome, all of which have pulmonary fibrosis as a clinical feature. Some of the genes included in the panel have an autosomal recessive inheritance pattern in those disorders, but individuals who are heterozygous for pathogenic variants in the genes may develop later-onset pulmonary fibrosis.'
Pulmonary fibrosis familial v0.2 MUC5B Arina Puzriakova changed review comment from: Single common SNP in the promoter of MUC5B confers susceptibility to idiopathic pulmonary fibrosis. Applicant review states, There are no known or published ethnic differences in detection rates, except for a low allele frequency of a MUC5B promotor SNP in Africans, which is known to be a risk allele for FPF. This SNP would be included in a gene panel for FPF; to: Single common SNP in the promoter of MUC5B confers susceptibility to idiopathic pulmonary fibrosis. Applicant review states, 'There are no known or published ethnic differences in detection rates, except for a low allele frequency of a MUC5B promotor SNP in Africans, which is known to be a risk allele for FPF. This SNP would be included in a gene panel for FPF'
Pulmonary fibrosis familial v0.2 ZCCHC8 Arina Puzriakova reviewed gene: ZCCHC8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Pulmonary fibrosis familial v0.2 TINF2 Arina Puzriakova reviewed gene: TINF2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Pulmonary fibrosis familial v0.2 TERT Arina Puzriakova reviewed gene: TERT: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Pulmonary fibrosis familial v0.2 TERC Arina Puzriakova reviewed gene: TERC: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Pulmonary fibrosis familial v0.2 SFTPC Arina Puzriakova reviewed gene: SFTPC: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Pulmonary fibrosis familial v0.2 SFTPB Arina Puzriakova reviewed gene: SFTPB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Pulmonary fibrosis familial v0.2 SFTPA2 Arina Puzriakova reviewed gene: SFTPA2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Pulmonary fibrosis familial v0.2 SFTPA1 Arina Puzriakova reviewed gene: SFTPA1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Pulmonary fibrosis familial v0.2 RTEL1 Arina Puzriakova reviewed gene: RTEL1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Pulmonary fibrosis familial v0.2 PARN Arina Puzriakova reviewed gene: PARN: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Pulmonary fibrosis familial v0.2 NOP10 Arina Puzriakova reviewed gene: NOP10: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Pulmonary fibrosis familial v0.2 NKX2-1 Arina Puzriakova reviewed gene: NKX2-1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Pulmonary fibrosis familial v0.2 NHP2 Arina Puzriakova reviewed gene: NHP2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Pulmonary fibrosis familial v0.2 NAF1 Arina Puzriakova reviewed gene: NAF1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Pulmonary fibrosis familial v0.2 MUC5B Arina Puzriakova commented on gene: MUC5B
Pulmonary fibrosis familial v0.2 MARS Arina Puzriakova reviewed gene: MARS: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Pulmonary fibrosis familial v0.2 HPS4 Arina Puzriakova reviewed gene: HPS4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Pulmonary fibrosis familial v0.2 HPS1 Arina Puzriakova reviewed gene: HPS1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Pulmonary fibrosis familial v0.2 DKC1 Arina Puzriakova reviewed gene: DKC1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Pulmonary fibrosis familial v0.2 CTC1 Arina Puzriakova reviewed gene: CTC1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Pulmonary fibrosis familial v0.2 CSF2RB Arina Puzriakova reviewed gene: CSF2RB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Pulmonary fibrosis familial v0.2 CSF2RA Arina Puzriakova reviewed gene: CSF2RA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Pulmonary fibrosis familial v0.2 AP3B1 Arina Puzriakova reviewed gene: AP3B1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Pulmonary fibrosis familial v0.2 ACD Arina Puzriakova reviewed gene: ACD: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Pulmonary fibrosis familial v0.2 ABCA3 Arina Puzriakova reviewed gene: ABCA3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Pulmonary fibrosis familial v0.1 ZCCHC8 Arina Puzriakova gene: ZCCHC8 was added
gene: ZCCHC8 was added to Pulmonary fibrosis familial. Sources: Expert Review Green
Mode of inheritance for gene: ZCCHC8 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ZCCHC8 were set to 31488579
Phenotypes for gene: ZCCHC8 were set to Pulmonary fibrosis and/or bone marrow failure, telomere-related, 5, OMIM:618674
Pulmonary fibrosis familial v0.1 TINF2 Arina Puzriakova gene: TINF2 was added
gene: TINF2 was added to Pulmonary fibrosis familial. Sources: Expert Review Green
Mode of inheritance for gene: TINF2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TINF2 were set to 18252230; 21477109
Phenotypes for gene: TINF2 were set to Dyskeratosis congenita, autosomal dominant 3, OMIM:613990
Pulmonary fibrosis familial v0.1 TERT Arina Puzriakova gene: TERT was added
gene: TERT was added to Pulmonary fibrosis familial. Sources: Expert Review Green
Mode of inheritance for gene: TERT was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TERT were set to 17392301; 27836952; 16247010
Phenotypes for gene: TERT were set to Pulmonary fibrosis and/or bone marrow failure, telomere-related, 1, OMIM:614742
Pulmonary fibrosis familial v0.1 TERC Arina Puzriakova gene: TERC was added
gene: TERC was added to Pulmonary fibrosis familial. Sources: Expert Review Green
Mode of inheritance for gene: TERC was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TERC were set to 17392301; 27836952; 20301408; 21436073
Phenotypes for gene: TERC were set to {Pulmonary fibrosis, idiopathic, susceptibility to}, OMIM:614743
Pulmonary fibrosis familial v0.1 SFTPC Arina Puzriakova gene: SFTPC was added
gene: SFTPC was added to Pulmonary fibrosis familial. Sources: Expert Review Green
Mode of inheritance for gene: SFTPC was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SFTPC were set to 11207353; 17005585; 20656946; 20301408
Phenotypes for gene: SFTPC were set to Surfactant metabolism dysfunction, pulmonary, 2, OMIM:610913
Pulmonary fibrosis familial v0.1 SFTPB Arina Puzriakova gene: SFTPB was added
gene: SFTPB was added to Pulmonary fibrosis familial. Sources: Expert Review Green
Mode of inheritance for gene: SFTPB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SFTPB were set to 8163685; 15331184
Phenotypes for gene: SFTPB were set to Surfactant metabolism dysfunction, pulmonary, 1, OMIM:265120
Pulmonary fibrosis familial v0.1 SFTPA2 Arina Puzriakova gene: SFTPA2 was added
gene: SFTPA2 was added to Pulmonary fibrosis familial. Sources: Expert Review Green
Mode of inheritance for gene: SFTPA2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SFTPA2 were set to 19100526; 26568241; 32855221
Phenotypes for gene: SFTPA2 were set to Interstitial lung disease 2, OMIM:178500
Pulmonary fibrosis familial v0.1 SFTPA1 Arina Puzriakova gene: SFTPA1 was added
gene: SFTPA1 was added to Pulmonary fibrosis familial. Sources: Expert Review Green
Mode of inheritance for gene: SFTPA1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: SFTPA1 were set to 30854216; 26792177; 32855221; 28869238; 31601679
Phenotypes for gene: SFTPA1 were set to Interstitial lung disease 1, OMIM:619611
Pulmonary fibrosis familial v0.1 RTEL1 Arina Puzriakova gene: RTEL1 was added
gene: RTEL1 was added to Pulmonary fibrosis familial. Sources: Expert Review Green
Mode of inheritance for gene: RTEL1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: RTEL1 were set to 23959892; 25607374; 25848748
Phenotypes for gene: RTEL1 were set to Pulmonary fibrosis and/or bone marrow failure, telomere-related, 3, OMIM:616373
Pulmonary fibrosis familial v0.1 PARN Arina Puzriakova gene: PARN was added
gene: PARN was added to Pulmonary fibrosis familial. Sources: Expert Review Green
Mode of inheritance for gene: PARN was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PARN were set to 26116823; 25848748
Phenotypes for gene: PARN were set to Pulmonary fibrosis and/or bone marrow failure, telomere-related, 4, OMIM:616371
Pulmonary fibrosis familial v0.1 NOP10 Arina Puzriakova gene: NOP10 was added
gene: NOP10 was added to Pulmonary fibrosis familial. Sources: Expert Review Green
Mode of inheritance for gene: NOP10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NOP10 were set to 17507419
Phenotypes for gene: NOP10 were set to Dyskeratosis congenita, autosomal recessive 1, OMIM:224230
Pulmonary fibrosis familial v0.1 NKX2-1 Arina Puzriakova gene: NKX2-1 was added
gene: NKX2-1 was added to Pulmonary fibrosis familial. Sources: Expert Review Green
Mode of inheritance for gene: NKX2-1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NKX2-1 were set to 19336474; 9565498; 23430038
Phenotypes for gene: NKX2-1 were set to Choreoathetosis, hypothyroidism, and neonatal respiratory distress, OMIM:610978
Pulmonary fibrosis familial v0.1 NHP2 Arina Puzriakova gene: NHP2 was added
gene: NHP2 was added to Pulmonary fibrosis familial. Sources: Expert Review Green
Mode of inheritance for gene: NHP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NHP2 were set to 31985013
Phenotypes for gene: NHP2 were set to Dyskeratosis congenita, autosomal recessive 2, OMIM:613987
Pulmonary fibrosis familial v0.1 NAF1 Arina Puzriakova gene: NAF1 was added
gene: NAF1 was added to Pulmonary fibrosis familial. Sources: Expert Review Green
Mode of inheritance for gene: NAF1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NAF1 were set to 27510903
Phenotypes for gene: NAF1 were set to Pulmonary fibrosis-emphysema
Pulmonary fibrosis familial v0.1 MUC5B Arina Puzriakova gene: MUC5B was added
gene: MUC5B was added to Pulmonary fibrosis familial. Sources: Expert Review Red
Mode of inheritance for gene: MUC5B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MUC5B were set to 21506748; 21506741
Phenotypes for gene: MUC5B were set to {Pulmonary fibrosis, idiopathic, susceptibility to}, OMIM:178500
Pulmonary fibrosis familial v0.1 MARS Arina Puzriakova gene: MARS was added
gene: MARS was added to Pulmonary fibrosis familial. Sources: Expert Review Green
Mode of inheritance for gene: MARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MARS were set to 32833345; 30271085; 24103465; 25913036
Phenotypes for gene: MARS were set to Interstitial lung and liver disease, OMIM:615486
Pulmonary fibrosis familial v0.1 HPS4 Arina Puzriakova gene: HPS4 was added
gene: HPS4 was added to Pulmonary fibrosis familial. Sources: Expert Review Green
Mode of inheritance for gene: HPS4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HPS4 were set to 11836498; 31415434; 20301464
Phenotypes for gene: HPS4 were set to Hermansky-Pudlak syndrome 4, OMIM:614073
Pulmonary fibrosis familial v0.1 HPS1 Arina Puzriakova gene: HPS1 was added
gene: HPS1 was added to Pulmonary fibrosis familial. Sources: Expert Review Green
Mode of inheritance for gene: HPS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HPS1 were set to 8896559; 31619213; 20301464
Phenotypes for gene: HPS1 were set to Hermansky-Pudlak syndrome 1, OMIM:203300
Pulmonary fibrosis familial v0.1 DKC1 Arina Puzriakova gene: DKC1 was added
gene: DKC1 was added to Pulmonary fibrosis familial. Sources: Expert Review Green
Mode of inheritance for gene: DKC1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: DKC1 were set to 21415081; 9590285; 24504062; 30868555; 23946118
Phenotypes for gene: DKC1 were set to Dyskeratosis congenita, X-linked, OMIM:305000
Pulmonary fibrosis familial v0.1 CTC1 Arina Puzriakova gene: CTC1 was added
gene: CTC1 was added to Pulmonary fibrosis familial. Sources: Expert Review Green
Mode of inheritance for gene: CTC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTC1 were set to 30891747; 33269665
Phenotypes for gene: CTC1 were set to Cerebroretinal microangiopathy with calcifications and cysts, OMIM:612199
Pulmonary fibrosis familial v0.1 CSF2RB Arina Puzriakova gene: CSF2RB was added
gene: CSF2RB was added to Pulmonary fibrosis familial. Sources: Expert Review Green
Mode of inheritance for gene: CSF2RB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CSF2RB were set to 15331184; 21075760
Phenotypes for gene: CSF2RB were set to Surfactant metabolism dysfunction, pulmonary, 5, OMIM:614370
Pulmonary fibrosis familial v0.1 CSF2RA Arina Puzriakova gene: CSF2RA was added
gene: CSF2RA was added to Pulmonary fibrosis familial. Sources: Expert Review Green
Mode of inheritance for gene: CSF2RA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CSF2RA were set to 18955570; 25425184
Phenotypes for gene: CSF2RA were set to Surfactant metabolism dysfunction, pulmonary, 4, OMIM:300770
Pulmonary fibrosis familial v0.1 AP3B1 Arina Puzriakova gene: AP3B1 was added
gene: AP3B1 was added to Pulmonary fibrosis familial. Sources: Expert Review Green
Mode of inheritance for gene: AP3B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP3B1 were set to 10024875; 22009278; 20301464
Phenotypes for gene: AP3B1 were set to Hermansky-Pudlak syndrome 2, OMIM:608233
Pulmonary fibrosis familial v0.1 ACD Arina Puzriakova gene: ACD was added
gene: ACD was added to Pulmonary fibrosis familial. Sources: Expert Review Green
Mode of inheritance for gene: ACD was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: ACD were set to Dyskeratosis congenita, autosomal dominant, OMIM:6
Pulmonary fibrosis familial v0.1 ABCA3 Arina Puzriakova gene: ABCA3 was added
gene: ABCA3 was added to Pulmonary fibrosis familial. Sources: Expert Review Green
Mode of inheritance for gene: ABCA3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABCA3 were set to 32238781; 15044640; 26780485; 24730976; 25553246
Phenotypes for gene: ABCA3 were set to Surfactant metabolism dysfunction, pulmonary, 3, OMIM:610921
Pulmonary fibrosis familial v0.0 Arina Puzriakova Added Panel Pulmonary fibrosis familial
Set list of related panels to R421
Set panel types to: GMS Rare Disease
Acute rhabdomyolysis v0.8 COQ8A Arina Puzriakova Classified gene: COQ8A as Green List (high evidence)
Acute rhabdomyolysis v0.8 COQ8A Arina Puzriakova Gene: coq8a has been classified as Green List (High Evidence).
Acute rhabdomyolysis v0.7 COQ4 Arina Puzriakova Classified gene: COQ4 as Green List (high evidence)
Acute rhabdomyolysis v0.7 COQ4 Arina Puzriakova Gene: coq4 has been classified as Green List (High Evidence).
Acute rhabdomyolysis v0.6 TYMP Arina Puzriakova commented on gene: TYMP: After NHS Genomic Medicine Service consideration, the rating of this gene has been left as Red but may be subject to review in the future.
Acute rhabdomyolysis v0.6 TSFM Arina Puzriakova commented on gene: TSFM: After NHS Genomic Medicine Service consideration, the rating of this gene has been left as Red but may be subject to review in the future.
Acute rhabdomyolysis v0.6 TSEN54 Arina Puzriakova commented on gene: TSEN54: After NHS Genomic Medicine Service consideration, the rating of this gene has been left as Red but may be subject to review in the future.
Acute rhabdomyolysis v0.6 TK2 Arina Puzriakova reviewed gene: TK2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 TANGO2 Arina Puzriakova reviewed gene: TANGO2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 SUCLA2 Arina Puzriakova commented on gene: SUCLA2: After NHS Genomic Medicine Service consideration, the rating of this gene has been left as Amber but may be subject to review in the future.
Acute rhabdomyolysis v0.6 SLC2A9 Arina Puzriakova commented on gene: SLC2A9: After NHS Genomic Medicine Service consideration, the rating of this gene has been left as Red but may be subject to review in the future.
Acute rhabdomyolysis v0.6 SLC22A5 Arina Puzriakova reviewed gene: SLC22A5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 SLC22A12 Arina Puzriakova commented on gene: SLC22A12: After NHS Genomic Medicine Service consideration, the rating of this gene has been left as Red but may be subject to review in the future.
Acute rhabdomyolysis v0.6 SIL1 Arina Puzriakova reviewed gene: SIL1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 SGCA Arina Puzriakova reviewed gene: SGCA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 SCN4A Arina Puzriakova reviewed gene: SCN4A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 RYR1 Arina Puzriakova reviewed gene: RYR1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 RRM2B Arina Puzriakova commented on gene: RRM2B: After NHS Genomic Medicine Service consideration, the rating of this gene has been left as Amber but may be subject to review in the future.
Acute rhabdomyolysis v0.6 RBCK1 Arina Puzriakova commented on gene: RBCK1: After NHS Genomic Medicine Service consideration, the rating of this gene has been left as Amber but may be subject to review in the future.
Acute rhabdomyolysis v0.6 PYGM Arina Puzriakova reviewed gene: PYGM: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 PRKAG2 Arina Puzriakova commented on gene: PRKAG2: After NHS Genomic Medicine Service consideration, the rating of this gene has been left as Amber but may be subject to review in the future.
Acute rhabdomyolysis v0.6 POLG2 Arina Puzriakova reviewed gene: POLG2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 POLG Arina Puzriakova reviewed gene: POLG: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 PHKG1 Arina Puzriakova commented on gene: PHKG1: After NHS Genomic Medicine Service consideration, the rating of this gene has been left as Red.
Acute rhabdomyolysis v0.6 PHKB Arina Puzriakova reviewed gene: PHKB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 PHKA1 Arina Puzriakova reviewed gene: PHKA1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 PGM1 Arina Puzriakova reviewed gene: PGM1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 PGK1 Arina Puzriakova reviewed gene: PGK1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 PGAM2 Arina Puzriakova reviewed gene: PGAM2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 PFKM Arina Puzriakova reviewed gene: PFKM: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 OBSCN Arina Puzriakova reviewed gene: OBSCN: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 MT-CO2 Arina Puzriakova reviewed gene: MT-CO2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 MT-CO1 Arina Puzriakova reviewed gene: MT-CO1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 LPIN1 Arina Puzriakova reviewed gene: LPIN1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 LDHA Arina Puzriakova reviewed gene: LDHA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 LAMP2 Arina Puzriakova reviewed gene: LAMP2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 ISCU Arina Puzriakova reviewed gene: ISCU: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 HADHB Arina Puzriakova reviewed gene: HADHB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 HADHA Arina Puzriakova reviewed gene: HADHA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 GYS1 Arina Puzriakova reviewed gene: GYS1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 GYG1 Arina Puzriakova reviewed gene: GYG1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 GMPPB Arina Puzriakova reviewed gene: GMPPB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 GBE1 Arina Puzriakova reviewed gene: GBE1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 GAA Arina Puzriakova reviewed gene: GAA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 FLAD1 Arina Puzriakova reviewed gene: FLAD1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 FKRP Arina Puzriakova reviewed gene: FKRP: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 FDX2 Arina Puzriakova reviewed gene: FDX2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 ETFDH Arina Puzriakova reviewed gene: ETFDH: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 ETFB Arina Puzriakova reviewed gene: ETFB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 ETFA Arina Puzriakova reviewed gene: ETFA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 ENO3 Arina Puzriakova reviewed gene: ENO3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 DYSF Arina Puzriakova reviewed gene: DYSF: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 DMD Arina Puzriakova reviewed gene: DMD: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 DGUOK Arina Puzriakova reviewed gene: DGUOK: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 CPT2 Arina Puzriakova reviewed gene: CPT2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 COQ8A Arina Puzriakova edited their review of gene: COQ8A: Added comment: This gene has been confirmed for this panel by the NHS Genomic Medicine Service and should be rated green.; Changed rating: GREEN
Acute rhabdomyolysis v0.6 COQ4 Arina Puzriakova edited their review of gene: COQ4: Added comment: This gene has been confirmed for this panel by the NHS Genomic Medicine Service and should be rated green.; Changed rating: GREEN
Acute rhabdomyolysis v0.6 CHKB Arina Puzriakova reviewed gene: CHKB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 CAV3 Arina Puzriakova edited their review of gene: CAV3: Added comment: This gene has been added to the panel on the recommendation of the NHS Genomic Medicine Service and should be rated green.; Changed rating: GREEN
Acute rhabdomyolysis v0.6 CACNA1S Arina Puzriakova reviewed gene: CACNA1S: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 ANO5 Arina Puzriakova reviewed gene: ANO5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 AMPD1 Arina Puzriakova reviewed gene: AMPD1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 ALDOA Arina Puzriakova reviewed gene: ALDOA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 AGL Arina Puzriakova reviewed gene: AGL: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 ACADVL Arina Puzriakova reviewed gene: ACADVL: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 ACADM Arina Puzriakova reviewed gene: ACADM: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.6 ACAD9 Arina Puzriakova reviewed gene: ACAD9: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Acute rhabdomyolysis v0.5 CYP2C8 Arina Puzriakova commented on gene: CYP2C8: Added 'to_be_confirmed_NHSE' tag - testing criteria to be discussed as CYP2C8-related rhabdomyolysis is drug-induced
Acute rhabdomyolysis v0.5 CYP2C8 Arina Puzriakova Tag to_be_confirmed_NHSE tag was added to gene: CYP2C8.
Acute rhabdomyolysis v0.5 CAV3 Arina Puzriakova Added comment: Comment on mode of inheritance: After NHS Genomic Medicine Service consideration, the mode of inheritance of this gene has been set to 'both mono and biallelic'.
Acute rhabdomyolysis v0.5 CAV3 Arina Puzriakova Mode of inheritance for gene: CAV3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Acute rhabdomyolysis v0.4 Arina Puzriakova List of related panels changed from to R419
Malignant hyperthermia v0.4 STAC3 Arina Puzriakova reviewed gene: STAC3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Malignant hyperthermia v0.4 RYR1 Arina Puzriakova reviewed gene: RYR1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Malignant hyperthermia v0.4 CACNA1S Arina Puzriakova reviewed gene: CACNA1S: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Autoinflammatory disorders v0.36 ADA2 Arina Puzriakova reviewed gene: ADA2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Autoinflammatory disorders v0.36 CARD14 Arina Puzriakova reviewed gene: CARD14: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Autoinflammatory disorders v0.36 TNFAIP3 Arina Puzriakova reviewed gene: TNFAIP3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Autoinflammatory disorders v0.36 TMEM173 Arina Puzriakova reviewed gene: TMEM173: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Autoinflammatory disorders v0.36 TNFRSF1A Arina Puzriakova reviewed gene: TNFRSF1A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Autoinflammatory disorders v0.36 SLC29A3 Arina Puzriakova reviewed gene: SLC29A3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Autoinflammatory disorders v0.36 SH3BP2 Arina Puzriakova edited their review of gene: SH3BP2: Added comment: This gene has been confirmed for this panel by the NHS Genomic Medicine Service and should be rated green.; Changed rating: GREEN
Autoinflammatory disorders v0.36 RBCK1 Arina Puzriakova reviewed gene: RBCK1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Autoinflammatory disorders v0.36 PSTPIP1 Arina Puzriakova reviewed gene: PSTPIP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Autoinflammatory disorders v0.36 PSMB9 Arina Puzriakova edited their review of gene: PSMB9: Added comment: This gene has been confirmed for this panel by the NHS Genomic Medicine Service and should be rated green.; Changed rating: GREEN
Autoinflammatory disorders v0.36 PSMB8 Arina Puzriakova reviewed gene: PSMB8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Autoinflammatory disorders v0.36 PSMB4 Arina Puzriakova edited their review of gene: PSMB4: Added comment: This gene has been confirmed for this panel by the NHS Genomic Medicine Service and should be rated green.; Changed rating: GREEN
Autoinflammatory disorders v0.36 PLCG2 Arina Puzriakova reviewed gene: PLCG2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Autoinflammatory disorders v0.36 OTULIN Arina Puzriakova reviewed gene: OTULIN: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Autoinflammatory disorders v0.36 NOD2 Arina Puzriakova reviewed gene: NOD2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Autoinflammatory disorders v0.36 NLRP3 Arina Puzriakova reviewed gene: NLRP3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Autoinflammatory disorders v0.36 NLRP12 Arina Puzriakova reviewed gene: NLRP12: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Autoinflammatory disorders v0.36 NLRC4 Arina Puzriakova reviewed gene: NLRC4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Autoinflammatory disorders v0.36 MVK Arina Puzriakova reviewed gene: MVK: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Autoinflammatory disorders v0.36 MEFV Arina Puzriakova reviewed gene: MEFV: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Autoinflammatory disorders v0.36 LPIN2 Arina Puzriakova reviewed gene: LPIN2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Autoinflammatory disorders v0.36 IL36RN Arina Puzriakova reviewed gene: IL36RN: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Autoinflammatory disorders v0.36 IL1RN Arina Puzriakova reviewed gene: IL1RN: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Autoinflammatory disorders v0.35 SH3BP2 Arina Puzriakova Classified gene: SH3BP2 as Green List (high evidence)
Autoinflammatory disorders v0.35 SH3BP2 Arina Puzriakova Gene: sh3bp2 has been classified as Green List (High Evidence).
Autoinflammatory disorders v0.34 PSMB9 Arina Puzriakova Classified gene: PSMB9 as Green List (high evidence)
Autoinflammatory disorders v0.34 PSMB9 Arina Puzriakova Gene: psmb9 has been classified as Green List (High Evidence).
Autoinflammatory disorders v0.33 PSMB4 Arina Puzriakova Classified gene: PSMB4 as Green List (high evidence)
Autoinflammatory disorders v0.33 PSMB4 Arina Puzriakova Gene: psmb4 has been classified as Green List (High Evidence).
Autoinflammatory disorders v0.32 UBA1 Arina Puzriakova commented on gene: UBA1: Added 'to_be_confirmed_NHSE' tag - gene to be further discussed due to somatic pathogenesis
Autoinflammatory disorders v0.32 UBA1 Arina Puzriakova Tag to_be_confirmed_NHSE tag was added to gene: UBA1.
Primary ovarian insufficiency v1.63 YTHDC2 Andrey Gagunashvili edited their review of gene: YTHDC2: Added comment: One more reference on association of YTHDC2 with primary ovarian insufficiency was added; Changed publications to: 29033321, 29360036, 35138268
Hereditary ataxia with onset in adulthood v2.139 ATP8A2 Sarah Leigh changed review comment from: Zornitza Stark has commented this gene is responsible for a congenital condition and not for an adult onset phenotype. However, table 1 in PMID 31612321 provides a review of the reported variants and their associated clinical features, where a few cases occur after adolescence. This provides some justification for this gene being green on this adult onset panel.
; to: Zornitza Stark has commented this gene is responsible for a congenital condition and not for an adult onset phenotype. Table 1 in PMID 31612321 provides a review of the reported variants and their associated clinical features, although cases are seen after adolescence, where data is available the onset is before 5 years of age. However, the report of a 27 year old male, without age of onset data (PMID: 22892528), provides some justification for this gene being green on this adult onset panel.
Thoracic aortic aneurysm or dissection (GMS) v1.18 LTBP3 Tracy Lester edited their review of gene: LTBP3: Changed rating: GREEN
Thoracic aortic aneurysm or dissection (GMS) v1.18 LTBP3 Tracy Lester gene: LTBP3 was added
gene: LTBP3 was added to Thoracic aortic aneurysm and dissection. Sources: NHS GMS
Mode of inheritance for gene: LTBP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LTBP3 were set to 25899461; 29625025
Phenotypes for gene: LTBP3 were set to Short stature; dental anomalies; aortopathy; facial dysmorphism; learning disability
Penetrance for gene: LTBP3 were set to unknown
Added comment: AR Short stature with dental anomalies (MIM601216) is an autosomal recessive disorder that can present with variable valvular and/or vascular defects, including mitral valve prolapse, aortic root dilation, and aortic as well as other arterial aneurysms. Pathogenic variant was alsmost missed as it was not tiered - not green on this panel and gene was on skeletal panel with only monoallelic mode of inheritance.
Sources: NHS GMS
Skeletal dysplasia v2.170 LTBP3 Tracy Lester edited their review of gene: LTBP3: Added comment: Dental anomalies with short stature is recessive. Several cases reported - pathogenic variant almost missed because gene was tiered under AD mode of inheritance only.; Changed publications to: 19213025, 25899461, 25669657, 19344874, 8721563; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Set current diagnostic: yes
Inherited white matter disorders v1.151 TWNK Arina Puzriakova Mode of inheritance for gene: TWNK was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Inherited white matter disorders v1.150 TWNK Arina Puzriakova Tag Q1_22_MOI was removed from gene: TWNK.
Hereditary neuropathy or pain disorder v1.81 TWNK Arina Puzriakova Mode of inheritance for gene: TWNK was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary neuropathy v1.433 TWNK Arina Puzriakova Mode of inheritance for gene: TWNK was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Radial dysplasia v1.16 LMBR1 Arina Puzriakova Mode of inheritance for gene: LMBR1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Choanal atresia v1.16 FGFR2 Arina Puzriakova Mode of inheritance for gene: FGFR2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Choanal atresia v1.15 FGFR2 Arina Puzriakova Tag Q1_22_MOI was removed from gene: FGFR2.
Deafness and congenital structural abnormalities v1.18 FGFR2 Arina Puzriakova Mode of inheritance for gene: FGFR2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Deafness and congenital structural abnormalities v1.17 FGFR2 Arina Puzriakova Tag Q1_22_MOI was removed from gene: FGFR2.
Intellectual disability v3.1500 FGFR2 Arina Puzriakova Mode of inheritance for gene: FGFR2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v3.1499 FGFR2 Arina Puzriakova Tag Q1_22_MOI was removed from gene: FGFR2.
Undiagnosed metabolic disorders v1.510 EXT1 Arina Puzriakova Mode of inheritance for gene: EXT1 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Undiagnosed metabolic disorders v1.509 EXT1 Arina Puzriakova Tag Q1_22_MOI was removed from gene: EXT1.
Undiagnosed metabolic disorders v1.509 DNM2 Arina Puzriakova Mode of inheritance for gene: DNM2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cholestasis v1.103 YARS Alison Bybee changed review comment from: Case report of homozygous biallelic variant inherited from heterozygous parents, child affected with complex clinical conditions culminating in death at 12 months of age. PMID 33490854 reports a case with failure to thrive and cholestatic hepatitis, followed by progressive liver disease, exocrine pancreatic insufficiency, acute renal failure, recurrent infections, ichthyosis, hematologic concerns, hypotonia, and global developmental delay, amongst other features. Autopsy confirmed significant end-stage fibrotic liver disease with cholestasis.
Sources: Literature; to: PMID 33490854 (2021) - Case report of homozygous biallelic variant inherited from heterozygous parents, child affected with complex clinical conditions culminating in death at 12 months of age. PMID 33490854 reports a case with failure to thrive and cholestatic hepatitis, followed by progressive liver disease, exocrine pancreatic insufficiency, acute renal failure, recurrent infections, ichthyosis, hematologic concerns, hypotonia, and global developmental delay, amongst other features. Autopsy confirmed significant end-stage fibrotic liver disease with cholestasis.
Sources: Literature
Cholestasis v1.103 ZFYVE19 Alison Bybee changed review comment from: PMID: 33853651 (2021) - Case report on Moroccan child with biallelic, predicted complete LoF variant in ZFYVE19 and heterozygous consanguineous parents. Patient had neonatal onset PFIC, high-GGT intrahepatic cholestasis, histopathological features of ductal plate malformation/congenital hepatic fibrosis, and cultured patient fibroblasts had features of ciliopathy.

Source: Literature.; to: PMID: 33853651 (2021) - Case report on Moroccan child with biallelic, predicted complete LoF variant in ZFYVE19 homozygous variant with heterozygous consanguineous parents. Patient had neonatal onset PFIC, high-GGT intrahepatic cholestasis, histopathological features of ductal plate malformation/congenital hepatic fibrosis, and cultured patient fibroblasts had features of ciliopathy.

Source: Literature.
Cholestasis v1.103 YARS Alison Bybee reviewed gene: YARS: Rating: GREEN; Mode of pathogenicity: None; Publications: 33490854; Phenotypes: failure to thrive (FTT), cholestatic hepatitis, progressive liver disease, exocrine pancreatic insufficiency, acute renal failure, recurrent infections, ichthyosis, hematologic concern, , hypotonia, global developmental delay; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.827 RAC3 Rhiannon Mellis gene: RAC3 was added
gene: RAC3 was added to Fetal anomalies. Sources: Literature,Expert Review,NHS GMS
Mode of inheritance for gene: RAC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAC3 were set to 30293988; 29276006
Phenotypes for gene: RAC3 were set to Abnormality of brain morphology; Abnormal muscle tone; Neurodevelopmental delay; Intellectual disability
Mode of pathogenicity for gene: RAC3 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: RAC3 was set to GREEN
Added comment: This gene already has sufficient evidence for Green rating on the ID panel (see below) and now adding evidence (from NHS GMS testing) for prenatal phenotype to support Green rating for the Fetal Anomalies panel also: A RAC3 likely pathogenic missense variant has been identified postnatally in a baby that presented prenatally with absent corpus callosum, bilateral ventriculomegaly, cerebellar and brainstem hypoplasia detected on fetal ultrasound and MRI. The variant is judged by the child's clinical team to be causative of the clinical and radiological features in the child.

Copied from Green review on Intellectual Disability panel by Konstantinos Varvagiannis:

PMID: 30293988 reports on 5 individuals (from 4 different families) with de novo missense variants in RAC3. All individuals demonstrated structural anomalies on brain MRI (notably agenesis/dysgenesis of the corpus callosum, variable degrees of polymicrogyria and ventricular anomalies) as well as shared non-specific neurological features including abnormal muscular tone, global developmental delay and severe to profound intellectual disability. Feeding difficulties were observed in 4/5 patients.

All variants reported are missense and are presumed to result in constitutive protein activation, as suggested by previous observations either in RAC3 [eg. the p.(Gln61Leu) mutation] or the highly homologous RAC1 and RAC2. According to the authors this is further supported by the fact that Rac3 -/- mice do not show a severe phenotype while missense variants are underrepresented in the ExAC database (z=1.97) as opposed to loss-of-function variants (pLI=0.04 / probability of loss-of-function intolerance).

Of the 3 SNVs reported, 2 variants were in adjacent amino-acid positions [p.(Gln61Leu) and p.(Glu62Lys)]. The latter variant was found in 2 half-sibs born to different fathers, due to suspected maternal gonadal mosaicism (variant absent in all sequencing reads in the maternal DNA sample). The specific variant was also found in a further affected individual from an unrelated family.

Finally, as the authors point out a further individual with de novo RAC3 missense variant [p.(Ala59Gly)] was reported previously in an individual with thin corpus callosum and global developmental delay, although the phenotype was felt to be more reminiscent of Robinow syndrome (PMID: 29276006).
Sources: Literature, Expert Review, NHS GMS
Intellectual disability v3.1499 FGFR2 Arina Puzriakova Tag Q1_22_MOI tag was added to gene: FGFR2.
Choanal atresia v1.15 FGFR2 Arina Puzriakova Tag Q1_22_MOI tag was added to gene: FGFR2.
Deafness and congenital structural abnormalities v1.17 FGFR2 Arina Puzriakova Tag Q1_22_MOI tag was added to gene: FGFR2.
Inherited white matter disorders v1.150 TWNK Arina Puzriakova Tag Q1_22_MOI tag was added to gene: TWNK.
Intellectual disability v3.1499 POLR1D Arina Puzriakova Phenotypes for gene: POLR1D were changed from Treacher Collins syndrome 2, 613717 to Treacher Collins syndrome 2, OMIM:613717
Structural eye disease v1.103 POLR1D Arina Puzriakova Phenotypes for gene: POLR1D were changed from Treacher-Collins Syndrome 2, 613717 to Treacher Collins syndrome 2, OMIM:613717
Intellectual disability v3.1498 POLR1D Arina Puzriakova Mode of inheritance for gene: POLR1D was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v1.102 POLR1D Arina Puzriakova Mode of inheritance for gene: POLR1D was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Clefting v2.61 POLR1D Arina Puzriakova Phenotypes for gene: POLR1D were changed from TREACHER COLLINS SYNDROME 2; TCS2 to Treacher Collins syndrome 2, OMIM:613717
Skeletal dysplasia v2.170 ANAPC1 Eleanor Williams Tag to_be_confirmed_NHSE tag was added to gene: ANAPC1.
Skeletal dysplasia v2.170 TNFRSF11A Eleanor Williams Tag to_be_confirmed_NHSE tag was added to gene: TNFRSF11A.
Membranoproliferative glomerulonephritis including C3 glomerulopathy v2.21 DGKE Eleanor Williams Tag to_be_confirmed_NHSE tag was added to gene: DGKE.
Membranoproliferative glomerulonephritis including C3 glomerulopathy v2.21 CFH Eleanor Williams Tag to_be_confirmed_NHSE tag was added to gene: CFH.
Membranoproliferative glomerulonephritis including C3 glomerulopathy v2.21 CFI Eleanor Williams Tag to_be_confirmed_NHSE tag was added to gene: CFI.
Membranoproliferative glomerulonephritis including C3 glomerulopathy v2.21 CFB Eleanor Williams Tag to_be_confirmed_NHSE tag was added to gene: CFB.
Atypical haemolytic uraemic syndrome v2.10 ADAMTS13 Eleanor Williams Tag to_be_confirmed_NHSE tag was added to gene: ADAMTS13.
Hereditary systemic amyloidosis v1.12 NLRP3 Eleanor Williams Tag to_be_confirmed_NHSE tag was added to gene: NLRP3.
Cholestasis v1.103 ZFYVE19 Alison Bybee reviewed gene: ZFYVE19: Rating: GREEN; Mode of pathogenicity: None; Publications: 33853651; Phenotypes: neonatal cholestasis, cilia dysfunction; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.1497 GJC2 Arina Puzriakova Phenotypes for gene: GJC2 were changed from Leukodystrophy, hypomyelinating, 2, 608804Spastic paraplegia 44, autosomal recessive, 613206Lymphedema, hereditary, IC, 613480; LYMPHEDEMA, HEREDITARY, IC to Leukodystrophy, hypomyelinating, 2, OMIM:608804
Childhood onset hereditary spastic paraplegia v2.123 GJC2 Arina Puzriakova Mode of inheritance for gene: GJC2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Undiagnosed metabolic disorders v1.508 EXT1 Arina Puzriakova Tag Q1_22_MOI tag was added to gene: EXT1.
Distal myopathies v1.39 DNM2 Arina Puzriakova Phenotypes for gene: DNM2 were changed from Myopathy, centronuclear, 160150 to Centronuclear myopathy 1, OMIM:160150
Monogenic hearing loss v2.218 GJB3 Eleanor Williams Tag to_be_confirmed_NHSE tag was added to gene: GJB3.
Undiagnosed metabolic disorders v1.508 DHTKD1 Arina Puzriakova Tag Q1_22_MOI tag was added to gene: DHTKD1.
Possible mitochondrial disorder - nuclear genes v1.65 DHTKD1 Arina Puzriakova Mode of inheritance for gene: DHTKD1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v2.86 DHTKD1 Arina Puzriakova Mode of inheritance for gene: DHTKD1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Stickler syndrome v2.24 COL11A2 Arina Puzriakova Phenotypes for gene: COL11A2 were changed from Otospondylomegaepiphyseal dysplasia, autosomal dominant, OMIM:184840 to Otospondylomegaepiphyseal dysplasia, autosomal dominant, OMIM:184840; Otospondylomegaepiphyseal dysplasia, autosomal recessive, OMIM:215150
Possible mitochondrial disorder - nuclear genes v1.64 HPDL Sarah Leigh Tag to_be_confirmed_NHSE tag was added to gene: HPDL.
Mitochondrial disorders v2.85 HPDL Sarah Leigh Tag to_be_confirmed_NHSE tag was added to gene: HPDL.
Pulmonary arterial hypertension v2.16 ABCC8 Ivone Leong Tag to_be_confirmed_NHSE tag was added to gene: ABCC8.
Pulmonary arterial hypertension v2.16 SARS2 Ivone Leong Tag to_be_confirmed_NHSE tag was added to gene: SARS2.
Hypophosphataemia or rickets v2.14 FAH Ivone Leong Tag to_be_confirmed_NHSE tag was added to gene: FAH.
Monogenic hearing loss v2.218 SOX2 Eleanor Williams Tag to_be_confirmed_NHSE tag was added to gene: SOX2.
Severe microcephaly v2.280 CCND2 Sarah Leigh Publications for gene: CCND2 were set to 34087052
Severe microcephaly v2.279 CCND2 Sarah Leigh edited their review of gene: CCND2: Added comment: Not associated with a phenotype in OMIM, Gen2Phen. At least three terminating variants have been reported in three unrelated cases with severe microcephaly. These variants are located within the proximal region of the gene, in contrast to the previously reported megalencephaly-associated CCND2 variants, which are localized to
the terminal exon, resulting in gain of function (PMID:34087052;24705253).; Changed rating: GREEN
Severe microcephaly v2.279 CCND2 Sarah Leigh Phenotypes for gene: CCND2 were changed from Microcephaly, MONDO# 0001149 to Microcephaly, MONDO:0001149
Severe microcephaly v2.278 CCND2 Sarah Leigh Classified gene: CCND2 as Amber List (moderate evidence)
Severe microcephaly v2.278 CCND2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Severe microcephaly v2.278 CCND2 Sarah Leigh Gene: ccnd2 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v2.277 CCND2 Sarah Leigh Tag Q1_22_rating tag was added to gene: CCND2.
COVID-19 research v1.115 CEBPE Arina Puzriakova Phenotypes for gene: CEBPE were changed from Specific granule deficiency 1; Recurrent infection due to specific granule deficiency; Congenital defects of phagocyte number or function; Specific granule deficiency, 245480; Neutrophils with bilobed nuclei; neutrophil lactoferrin deficiency; CCAAT/enhancer binding protein epsilon deficiency (CEBPE) to Specific granule deficiency, OMIM:245480; CCAAT/enhancer binding protein epsilon deficiency (CEBPE); Recurrent infection due to specific granule deficiency; Neutrophil lactoferrin deficiency; Neutrophils with bilobed nuclei; Congenital defects of phagocyte number or function
Primary immunodeficiency or monogenic inflammatory bowel disease v2.527 CEBPE Arina Puzriakova Phenotypes for gene: CEBPE were changed from Specific granule deficiency, 245480; Specific granule deficiency 1; CCAAT/enhancer binding protein epsilon deficiency (CEBPE); Recurrent infection due to specific granule deficiency; neutrophil lactoferrin deficiency; Neutrophils with bilobed nuclei; Congenital defects of phagocyte number or function to Specific granule deficiency, OMIM:245480; CCAAT/enhancer binding protein epsilon deficiency (CEBPE); Recurrent infection due to specific granule deficiency; Neutrophil lactoferrin deficiency; Neutrophils with bilobed nuclei; Congenital defects of phagocyte number or function
DDG2P v2.61 ANTXR1 Arina Puzriakova Phenotypes for gene: ANTXR1 were changed from GAPO SYNDROME to GAPO syndrome, OMIM:230740
Fetal anomalies v1.827 ANTXR1 Arina Puzriakova Phenotypes for gene: ANTXR1 were changed from GAPO SYNDROME to GAPO syndrome, OMIM:230740
Vascular skin disorders v1.48 ANTXR1 Arina Puzriakova Phenotypes for gene: ANTXR1 were changed from Susceptibility to infantile haemangioma to {?Hemangioma, capillary infantile, susceptibility to}, OMIM:602089
Cerebral vascular malformations v2.59 ANTXR1 Arina Puzriakova Phenotypes for gene: ANTXR1 were changed from {Hemangioma, capillary infantile, susceptibility to}, 602089; {Hemangioma, capillary infantile, susceptibility to} to {?Hemangioma, capillary infantile, susceptibility to} , OMIM:602089
PHACE(S) syndrome v1.3 ANTXR1 Arina Puzriakova Phenotypes for gene: ANTXR1 were changed from {Hemangioma, capillary infantile, susceptibility to}, 602089 to {?Hemangioma, capillary infantile, susceptibility to} , OMIM:602089
Hyperthyroidism v2.11 ALB Arina Puzriakova Publications for gene: ALB were set to 29163366; 8064810; 24646103; 27834068
Hyperthyroidism v2.10 ALB Arina Puzriakova Added comment: Comment on mode of inheritance: Most cases of familial dysalbuminaemic hyperthyroxinaemia (FDH) are associated with heterozygous variants in the albumin gene. Only one report to date of a biallelic variant causing FDH (PMID: 29676214) where the proband displayed a greater increase in T4 relative to that observed in heterozygous family members. As there are no further biallelic FDH cases and the recessive phenotype of congenital analbuminemia (also associated with this gene) is not relevant to this panel, the MOI of 'monoallelic' inheritance will be maintained at this time.
Hyperthyroidism v2.10 ALB Arina Puzriakova Mode of inheritance for gene: ALB was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hyperthyroidism v2.9 ALB Arina Puzriakova Phenotypes for gene: ALB were changed from Familial dysalbuminaemic hyperthyroxinaemia; [Dysalbuminemic hyperthyroxinemia], 615999 to Familial dysalbuminaemic hyperthyroxinaemia; [Dysalbuminemic hyperthyroxinemia], OMIM:615999; ?[Dysalbuminemic hypertriiodothyroninemia], OMIM:615999
Gastrointestinal neuromuscular disorders v1.18 IDS Donna Bernstein reviewed gene: IDS: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 15797184; Phenotypes: Elevated urine glycosamino glycans, heparan and dermatan sulphate due to deficient iduronate 2-sulphatase activity, short stature, dysostosis multiplex, wide spaced teeth: kyphosis, hyrdocephalus, hearing loss, sleep apnea, facial coarsening, hernia, macrocephaly, macroglossia, joint stffness, hepatosplenomegaly, airway obstruction, seizures, cardiovascular valve disease, may have normal intelligence or CNS involvement; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v3.147 KIF26B Zornitza Stark gene: KIF26B was added
gene: KIF26B was added to Arthrogryposis. Sources: Literature
Mode of inheritance for gene: KIF26B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIF26B were set to 30151950
Phenotypes for gene: KIF26B were set to Progressive microcephaly, pontocerebellar hypoplasia, and arthrogryposis
Review for gene: KIF26B was set to RED
Added comment: 1 report only of infant with progressive microcephaly, pontocerebellar hypoplasia, and arthrogryposis secondary to the involvement of anterior horn cells and ventral (motor) nerves. Whole exome sequencing on the trio identified a de novo KIF26B missense variant (p.Gly546Ser). Functional analysis of the variant protein in cultured cells revealed a reduction in the KIF26B protein's ability to promote cell adhesion, a defect that potentially contributes to its pathogenicity.
Sources: Literature
Renal ciliopathies v1.49 CYS1 Zornitza Stark gene: CYS1 was added
gene: CYS1 was added to Renal ciliopathies. Sources: Literature
Mode of inheritance for gene: CYS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYS1 were set to 34521872
Phenotypes for gene: CYS1 were set to Polycystic kidney disease, MONDO:0020642
Review for gene: CYS1 was set to AMBER
Added comment: Single family reported. However, extensive experimental data, including mouse model.
Sources: Literature
Mitochondrial disorders v2.85 UQCRC2 Zornitza Stark edited their review of gene: UQCRC2: Added comment: PMID 33865955: homozygous novel variant (p.Gly222Ala) reported. Functional studies showed impaired fibroblast respiratory chain function, western abnormalities, and altered mitochondrial ultrastructural abnormalities and of the mitochondrial network. Expression of a wild type vector in patient fibroblasts led to some restoration of function, but that part of the work was not stellar.; Changed rating: GREEN; Changed publications to: 28275242, 33865955
Fetal anomalies v1.826 MYL9 Zornitza Stark changed review comment from: unrelated families

Possibly 4th in PMID: 33264186 but specifics including genotype were lacking and overlapping institute/hospital as PMID: 33031641; to: Three unrelated families

Possibly 4th in PMID: 33264186 but specifics including genotype were lacking and overlapping institute/hospital as PMID: 33031641
Fetal anomalies v1.826 MYL9 Zornitza Stark edited their review of gene: MYL9: Added comment: unrelated families

Possibly 4th in PMID: 33264186 but specifics including genotype were lacking and overlapping institute/hospital as PMID: 33031641; Changed rating: GREEN; Changed publications to: 29453416, 33031641, 32621347, 33264186; Changed phenotypes to: Megacystis-microcolon-intestinal hypoperistalsis syndrome, MIM#619365
Mitochondrial disorders v2.85 ATP5A1 Zornitza Stark reviewed gene: ATP5A1: Rating: AMBER; Mode of pathogenicity: None; Publications: 34954817; Phenotypes: feeding intolerance, failure to thrive, hyperammonemia, lactic acidemia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Childhood onset dystonia, chorea or related movement disorder v1.210 ATP5G3 Zornitza Stark gene: ATP5G3 was added
gene: ATP5G3 was added to Childhood onset dystonia or chorea or related movement disorder. Sources: Literature
Mode of inheritance for gene: ATP5G3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP5G3 were set to 34636445; 34954817
Phenotypes for gene: ATP5G3 were set to Dystonia, early-onset, and/or spastic paraplegia, MIM# 619681
Review for gene: ATP5G3 was set to GREEN
Added comment: Note that HGNC approved gene name is ATP5MC3.

PMID: 34636445 reports a missense variant identified in a large single-family pedigree with dystonia and spastic paraplegia. The variant was identified via exome sequencing of the proband and a distant cousin, focussing on variants within the previously determined linkage region. The identical missense variant was also identified in a patient with childhood onset dystonic syndrome and was shown to be de novo. Functional studies of fibroblast cell lines from affected father (HSP) and proband of large family demonstrated decreased complex V function. A drosophila model containing the missense variant had reduced mobility and reduced complex V activity.

PMID: 34954817 reports de novo monoallelic missense variants in three individuals, however one of these individuals was reported in above paper. The other two patients were: (1) a-15-year-old girl with milestone delay, pyramidal signs, and generalized dystonia with prominent upper-body involvement, and (2) a 6-year-old boy with delayed psychomotor development, lower-extremity spasticity, and elevated blood lactate levels
Sources: Literature
Intellectual disability v3.1496 PRKAR1B Zornitza Stark reviewed gene: PRKAR1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 33833410; Phenotypes: Marbach-Schaaf neurodevelopmental syndrome MIM#619680; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Severe microcephaly v2.277 CCND2 Zornitza Stark gene: CCND2 was added
gene: CCND2 was added to Severe microcephaly. Sources: Literature
Mode of inheritance for gene: CCND2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CCND2 were set to 34087052
Phenotypes for gene: CCND2 were set to Microcephaly, MONDO# 0001149
Review for gene: CCND2 was set to GREEN
Added comment: Novel phenotype of microcephaly and mild developmental delay described in three unrelated families. Variants associated with this phenotype located in the proximal region of the gene.

Variants in distal region of gene associated with a reciprocal phenotype of macrocephaly/megalencephaly with severe cortical malformation.
Sources: Literature
Rare multisystem ciliopathy disorders v1.157 TOPORS Zornitza Stark reviewed gene: TOPORS: Rating: AMBER; Mode of pathogenicity: None; Publications: 34132027; Phenotypes: Ciliopathy, MONDO:0005308, TOPORS-associated, AR; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital muscular dystrophy v2.21 HNRNPA2B1 Sarah Leigh commented on gene: HNRNPA2B1: The Q1_22_rating tag has been added as the GMS review for this gene has not been received to date
Congenital muscular dystrophy v2.21 HNRNPA2B1 Sarah Leigh Tag Q1_22_rating tag was added to gene: HNRNPA2B1.
Skeletal dysplasia v2.170 CSNK1G1 Sarah Leigh Classified gene: CSNK1G1 as Amber List (moderate evidence)
Skeletal dysplasia v2.170 CSNK1G1 Sarah Leigh Gene: csnk1g1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.169 CSNK1G1 Sarah Leigh gene: CSNK1G1 was added
gene: CSNK1G1 was added to Skeletal dysplasia. Sources: NHS GMS
Q1_22_rating tags were added to gene: CSNK1G1.
Mode of inheritance for gene: CSNK1G1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CSNK1G1 were set to 24463883; 33009664
Phenotypes for gene: CSNK1G1 were set to early-onset epileptic encephalopathy and microcephaly
Review for gene: CSNK1G1 was set to AMBER
Added comment: Not associated with relevant phenotype in OMIM and as limited evidence on Gen2Phen for association with early-onset epileptic encephalopathy and microcephaly.
NHS Genomic Medicine Service review of CSNK1G1 on the Intellectual disability panel, recommended that CSNK1G1 should be made amber / green on the skeletal dysplasia panel; as skeletal features were reported in 2/5 reported cases (PMID: 33009664)TL.
Sources: NHS GMS
Early onset or syndromic epilepsy v2.489 CSNK1G1 Sarah Leigh changed review comment from: Comment on list classification: NHS Genomic Medicine Service review of CSNK1G1 on the Intellectual disability panel, recommended that CSNK1G1 should be made amber on the Genetic epilepsy syndromes panel; as epilepsy was seen in 2/5 reported cases (PMID: 33009664).


Amber for epilepsy panel R59

review of on the Intellectual disability; to: Comment on list classification: NHS Genomic Medicine Service review of CSNK1G1 on the Intellectual disability panel, recommended that CSNK1G1 should be made amber on the Genetic epilepsy syndromes panel; as epilepsy was seen in 2/5 reported cases (PMID: 33009664).
Early onset or syndromic epilepsy v2.489 CSNK1G1 Sarah Leigh Publications for gene: CSNK1G1 were set to 24463883
Early onset or syndromic epilepsy v2.488 CSNK1G1 Sarah Leigh Classified gene: CSNK1G1 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v2.488 CSNK1G1 Sarah Leigh Added comment: Comment on list classification: NHS Genomic Medicine Service review of CSNK1G1 on the Intellectual disability panel, recommended that CSNK1G1 should be made amber on the Genetic epilepsy syndromes panel; as epilepsy was seen in 2/5 reported cases (PMID: 33009664).


Amber for epilepsy panel R59

review of on the Intellectual disability
Early onset or syndromic epilepsy v2.488 CSNK1G1 Sarah Leigh Gene: csnk1g1 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v1.80 SLC12A6 Sarah Leigh edited their review of gene: SLC12A6: Added comment: In reviewing SLC12A6 on the Intellectual disabily panel, it was suggested that this gene should be green on this panel (source NHS Genomic Medicine Service).; Changed rating: GREEN
Hereditary neuropathy or pain disorder v1.80 SLC12A6 Sarah Leigh Tag Q1_22_rating tag was added to gene: SLC12A6.
Intellectual disability v3.1496 SLC35F1 Zornitza Stark gene: SLC35F1 was added
gene: SLC35F1 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: SLC35F1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC35F1 were set to 33821533
Phenotypes for gene: SLC35F1 were set to Neruodevelopmental disorder, MONDO:0700092, SLC35F1-associated; Rett-like syndrome
Review for gene: SLC35F1 was set to RED
Added comment: WES identified a de novo heterozygous c.1037T>C; p.(I346T) (absent in gnomad v2 and v3) in a female described to have Rett-like syndrome.

Global developmental delay, generalized tonic andtonic–clonic seizure, never acquired independent walking and developed spastictetraplegia in adulthood and limited speech

No functional data
Sources: Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v2.526 TLR8 Zornitza Stark changed review comment from: PMID 34981838: Monozygotic male twins, hemizygous for the G572V (maternally inherited), who had severe autoimmune haemolytic anaemia (AIHA) worsening with infections, and autoinflammation presenting as fevers, enteritis, arthritis and CNS vasculitis. Functional showed variant causes impaired stability of the TLR8 protein, cross-reactivity to TLR7 ligands and reduced ability of TLR8 to attenuate TLR7 signaling.; to: PMID 34981838: Monozygotic male twins, hemizygous for the G572V (maternally inherited), who had severe autoimmune haemolytic anaemia (AIHA) worsening with infections, and autoinflammation presenting as fevers, enteritis, arthritis and CNS vasculitis. Functional showed variant causes impaired stability of the TLR8 protein, cross-reactivity to TLR7 ligands and reduced ability of TLR8 to attenuate TLR7 signaling.

Further evidence for germline variants causing disease.
Primary immunodeficiency or monogenic inflammatory bowel disease v2.526 TLR8 Zornitza Stark reviewed gene: TLR8: Rating: GREEN; Mode of pathogenicity: None; Publications: 34981838; Phenotypes: Immunodeficiency, bone marrow failure, Autoinflammatory syndrome MONDO:0019751; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Primary immunodeficiency or monogenic inflammatory bowel disease v2.526 CRACR2A Zornitza Stark gene: CRACR2A was added
gene: CRACR2A was added to Primary immunodeficiency. Sources: Literature
Mode of inheritance for gene: CRACR2A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CRACR2A were set to PMID:34908525
Phenotypes for gene: CRACR2A were set to late onset combined immunodeficiency
Review for gene: CRACR2A was set to RED
Added comment: PMID:34908525 - one patient compound het (missense and PTC) with late onset combined immunodeficiency (current chest infections, panhypogammaglobulinemia and CD4+T cell lymphopenia). Functional studies showed defective JNK phosphorylation, defective SOCE and impaired cytokine production.
Sources: Literature
Cystic kidney disease v2.31 IFT140 Zornitza Stark reviewed gene: IFT140: Rating: GREEN; Mode of pathogenicity: None; Publications: 22503633, 23418020, 34890546; Phenotypes: Short-rib thoracic dysplasia 9 with or without polydactyly, MIM# 266920, MONDO:0009964, Cystic Kidney Disease, MONDO# 0002473, IFT140-related, dominant; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Differences in sex development v2.55 PRDM13 Zornitza Stark gene: PRDM13 was added
gene: PRDM13 was added to Disorders of sex development. Sources: Literature
Mode of inheritance for gene: PRDM13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRDM13 were set to 34730112
Phenotypes for gene: PRDM13 were set to congenital hypogonadotropic hypogonadism, MONDO:0015770
Review for gene: PRDM13 was set to AMBER
Added comment: Recessive disease causing ID and DSD described in three unrelated families (2 consanguineous), but all are from Malta, and all share the same 13bp deletion spanning an exon-intron boundary, so likely founder effect.

Mouse KO is embryonically lethal, and tissue specific KO failed to replicate many of the patients phenotypes, other than hypoplasia of the cerebellar vermis and hemispheres.
Sources: Literature
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.64 PPIA Zornitza Stark gene: PPIA was added
gene: PPIA was added to Early onset dementia (encompassing fronto-temporal dementia and prion disease). Sources: Literature
Mode of inheritance for gene: PPIA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPIA were set to 34972208
Phenotypes for gene: PPIA were set to amyotrophic lateral sclerosis, MONDO:0004976
Review for gene: PPIA was set to RED
Added comment: Paper characterizes a knockout mouse model that recapitulates key features of ALS-FTD. Also identified a heterozygous missense variant in one patient with sporadic amyotrophic lateral sclerosis. Functional studies of the missense variant suggest loss-of-function.
Sources: Literature
Primary ovarian insufficiency v1.63 PRDM9 Zornitza Stark gene: PRDM9 was added
gene: PRDM9 was added to Primary ovarian insufficiency. Sources: Literature
Mode of inheritance for gene: PRDM9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PRDM9 were set to 34257419
Phenotypes for gene: PRDM9 were set to Premature ovarian insufficiency
Review for gene: PRDM9 was set to GREEN
Added comment: 3 pathogenic heterozygous variants in PRDM9 identified in 4 patients with POI. Functional studies showed the variants in PRDM9 impaired its methyltransferase activity. Prdm9+/- mice were subfertile, and showed increased percentage of germ cells at abnormal pachytene stage with decreased number of PRDM9-dependent DSBs and insufficient recombination.
Sources: Literature
Skeletal dysplasia v2.168 GPX4 Zornitza Stark changed review comment from: PMID: 32827718
1x consaguineous family with 2x infants who died within first week of life. Homozygous frameshift variant.; to: PMID: 32827718
New consaguineous family with 2x infants who died within first week of life. Homozygous frameshift variant.
Skeletal dysplasia v2.168 GPX4 Zornitza Stark reviewed gene: GPX4: Rating: GREEN; Mode of pathogenicity: None; Publications: 24706940, 32827718; Phenotypes: Spondylometaphyseal dysplasia, Sedaghatian type MIM#250220; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.1496 CSTF2 Zornitza Stark reviewed gene: CSTF2: Rating: AMBER; Mode of pathogenicity: None; Publications: 32816001; Phenotypes: Intellectual disability; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Retinal disorders v2.242 ARL13B Ronnie Wright reviewed gene: ARL13B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v2.526 ANGPT1 Boaz Palterer gene: ANGPT1 was added
gene: ANGPT1 was added to Primary immunodeficiency. Sources: Literature
Mode of inheritance for gene: ANGPT1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ANGPT1 were set to 28601681
Phenotypes for gene: ANGPT1 were set to Hereditary Angioedema
Penetrance for gene: ANGPT1 were set to unknown
Review for gene: ANGPT1 was set to AMBER
Added comment: Sources: Literature
Fetal anomalies v1.826 CDX2 Dmitrijs Rots gene: CDX2 was added
gene: CDX2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: CDX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CDX2 were set to PMID: 34671974
Phenotypes for gene: CDX2 were set to Multiple congenital anomalies
Penetrance for gene: CDX2 were set to unknown
Review for gene: CDX2 was set to GREEN
Added comment: Multiple patients reported and summarized in PMID: 34671974 with multiple congenital anomalies, including patients with VACTERL-like phenotype.
Sources: Literature
VACTERL-like phenotypes v1.32 CDX2 Dmitrijs Rots gene: CDX2 was added
gene: CDX2 was added to VACTERL-like phenotypes. Sources: Literature
Mode of inheritance for gene: CDX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CDX2 were set to PMID: 34671974
Phenotypes for gene: CDX2 were set to Multiple congenital anomalies
Penetrance for gene: CDX2 were set to unknown
Review for gene: CDX2 was set to GREEN
Added comment: Multiple patients reported and summarized in PMID: 34671974 with multiple congenital anomalies, including patients with VACTERL-like phenotype.
Sources: Literature
Extreme early-onset hypertension v1.14 TTC21B John Sayer gene: TTC21B was added
gene: TTC21B was added to Extreme early-onset hypertension. Sources: Expert Review
Mode of inheritance for gene: TTC21B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTC21B were set to 24876116; 26940125; 34957165; 34805047
Phenotypes for gene: TTC21B were set to Hypertension; focal segmental glomerulosclerosis; nephronopthisis; myopia
Penetrance for gene: TTC21B were set to Complete
Review for gene: TTC21B was set to GREEN
gene: TTC21B was marked as current diagnostic
Added comment: There is growing evidence that severe hypertension is a common phenotype in patients with this gene mutation (TTC21B biallelic).
Sources: Expert Review
Fetal anomalies v1.826 CNBP Arina Puzriakova commented on gene: CNBP: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed. Confirmed with Rhiannon Mellis (GOSH) that the CNBP gene should remain as Red.
Rare syndromic craniosynostosis or isolated multisuture synostosis v2.61 NFIA Helen Lord reviewed gene: NFIA: Rating: GREEN; Mode of pathogenicity: None; Publications: 35080095, 31754721, 33288889; Phenotypes: Metopic synostosis, hydrocephalus, thin corpus callosum, mild developmental delay, autism, macrocephaly; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Retinal disorders v2.242 CTNNA1 Ivone Leong Tag Q1_22_NHS_review tag was added to gene: CTNNA1.
Pancreatitis v2.10 TRPV6 Ivone Leong Tag Q1_22_NHS_review tag was added to gene: TRPV6.
Cholestasis v1.103 TRMU Ivone Leong Tag Q1_22_NHS_review tag was added to gene: TRMU.
Cholestasis v1.103 SMPD1 Ivone Leong Tag Q1_22_NHS_review tag was added to gene: SMPD1.
Cholestasis v1.103 RINT1 Ivone Leong Tag Q1_22_NHS_review tag was added to gene: RINT1.
Cholestasis v1.103 POLG Ivone Leong Tag Q1_22_NHS_review tag was added to gene: POLG.
Cholestasis v1.103 NBAS Ivone Leong Tag Q1_22_NHS_review tag was added to gene: NBAS.
Cholestasis v1.103 MVK Ivone Leong Tag Q1_22_NHS_review tag was added to gene: MVK.
Cholestasis v1.103 HADHA Ivone Leong Tag Q1_22_NHS_review tag was added to gene: HADHA.
Cholestasis v1.103 GBE1 Ivone Leong Tag Q1_22_NHS_review tag was added to gene: GBE1.
Cholestasis v1.103 GALK1 Ivone Leong Tag Q1_22_NHS_review tag was added to gene: GALK1.
Cholestasis v1.103 GALE Ivone Leong Tag Q1_22_NHS_review tag was added to gene: GALE.
Paediatric or syndromic cardiomyopathy v1.61 SPRED2 Ivone Leong Entity copied from Intellectual disability v3.1496
Paediatric or syndromic cardiomyopathy v1.61 SPRED2 Ivone Leong gene: SPRED2 was added
gene: SPRED2 was added to Cardiomyopathies - including childhood onset. Sources: Literature,Expert Review Amber
Q1_22_rating tags were added to gene: SPRED2.
Mode of inheritance for gene: SPRED2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPRED2 were set to 34626534
Phenotypes for gene: SPRED2 were set to developmental delay; intellectual disability; cardiac defects; short stature; skeletal anomalies; a typical facial gestalt
Familial non syndromic congenital heart disease v1.73 SPRED2 Ivone Leong Classified gene: SPRED2 as Green List (high evidence)
Familial non syndromic congenital heart disease v1.73 SPRED2 Ivone Leong Added comment: Comment on list classification: There is enough evidence for this gene to be Green.
Familial non syndromic congenital heart disease v1.73 SPRED2 Ivone Leong Gene: spred2 has been classified as Green List (High Evidence).
Familial non syndromic congenital heart disease v1.72 SPRED2 Ivone Leong Tag Q1_22_rating was removed from gene: SPRED2.
Familial non syndromic congenital heart disease v1.72 SPRED2 Ivone Leong Entity copied from Intellectual disability v3.1496
Familial non syndromic congenital heart disease v1.72 SPRED2 Ivone Leong gene: SPRED2 was added
gene: SPRED2 was added to Familial non syndromic congenital heart disease. Sources: Expert Review Amber,Literature
Q1_22_rating tags were added to gene: SPRED2.
Mode of inheritance for gene: SPRED2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPRED2 were set to 34626534
Phenotypes for gene: SPRED2 were set to developmental delay; intellectual disability; cardiac defects; short stature; skeletal anomalies; a typical facial gestalt
RASopathies v1.77 SPRED2 Ivone Leong Classified gene: SPRED2 as Green List (high evidence)
RASopathies v1.77 SPRED2 Ivone Leong Added comment: Comment on list classification: There is enough evidence for this gene to be Green.
RASopathies v1.77 SPRED2 Ivone Leong Gene: spred2 has been classified as Green List (High Evidence).
RASopathies v1.76 SPRED2 Ivone Leong Tag Q1_22_rating was removed from gene: SPRED2.
RASopathies v1.76 SPRED2 Ivone Leong Entity copied from Intellectual disability v3.1496
RASopathies v1.76 SPRED2 Ivone Leong gene: SPRED2 was added
gene: SPRED2 was added to RASopathies. Sources: Literature,Expert Review Amber
Q1_22_rating tags were added to gene: SPRED2.
Mode of inheritance for gene: SPRED2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPRED2 were set to 34626534
Phenotypes for gene: SPRED2 were set to developmental delay; intellectual disability; cardiac defects; short stature; skeletal anomalies; a typical facial gestalt
Intellectual disability v3.1496 SPRED2 Ivone Leong Tag Q1_22_rating tag was added to gene: SPRED2.
Intellectual disability v3.1496 SPRED2 Ivone Leong Classified gene: SPRED2 as Amber List (moderate evidence)
Intellectual disability v3.1496 SPRED2 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in Gene2Phenotype (Strong) but not in OMIM. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Intellectual disability v3.1496 SPRED2 Ivone Leong Gene: spred2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v3.1496 SPRED2 Ivone Leong Classified gene: SPRED2 as Amber List (moderate evidence)
Intellectual disability v3.1496 SPRED2 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in Gene2Phenotype (Strong) but not in OMIM. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Intellectual disability v3.1496 SPRED2 Ivone Leong Gene: spred2 has been classified as Amber List (Moderate Evidence).
Early onset dystonia v1.105 SPATA5L1 Ivone Leong Classified gene: SPATA5L1 as Green List (high evidence)
Early onset dystonia v1.105 SPATA5L1 Ivone Leong Added comment: Comment on list classification: There is enough evidence for this gene to be Green.
Early onset dystonia v1.105 SPATA5L1 Ivone Leong Gene: spata5l1 has been classified as Green List (High Evidence).
Early onset dystonia v1.104 SPATA5L1 Ivone Leong Tag Q1_22_rating was removed from gene: SPATA5L1.
Early onset dystonia v1.104 SPATA5L1 Ivone Leong Entity copied from Intellectual disability v3.1495
Early onset dystonia v1.104 SPATA5L1 Ivone Leong gene: SPATA5L1 was added
gene: SPATA5L1 was added to Early onset dystonia. Sources: Literature,Expert Review Amber
Q1_22_rating tags were added to gene: SPATA5L1.
Mode of inheritance for gene: SPATA5L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPATA5L1 were set to 34626583
Phenotypes for gene: SPATA5L1 were set to Neurodevelopmental disorder with hearing loss and spasticity, OMIM:619616
Childhood onset dystonia, chorea or related movement disorder v1.210 SPATA5L1 Ivone Leong Entity copied from Intellectual disability v3.1495
Childhood onset dystonia, chorea or related movement disorder v1.210 SPATA5L1 Ivone Leong gene: SPATA5L1 was added
gene: SPATA5L1 was added to Childhood onset dystonia or chorea or related movement disorder. Sources: Literature,Expert Review Amber
Q1_22_rating tags were added to gene: SPATA5L1.
Mode of inheritance for gene: SPATA5L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPATA5L1 were set to 34626583
Phenotypes for gene: SPATA5L1 were set to Neurodevelopmental disorder with hearing loss and spasticity, OMIM:619616
Childhood onset hereditary spastic paraplegia v2.122 SPATA5L1 Ivone Leong Entity copied from Intellectual disability v3.1495
Childhood onset hereditary spastic paraplegia v2.122 SPATA5L1 Ivone Leong gene: SPATA5L1 was added
gene: SPATA5L1 was added to Hereditary spastic paraplegia - childhood onset. Sources: Expert Review Amber,Literature
Q1_22_rating tags were added to gene: SPATA5L1.
Mode of inheritance for gene: SPATA5L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPATA5L1 were set to 34626583
Phenotypes for gene: SPATA5L1 were set to Neurodevelopmental disorder with hearing loss and spasticity, OMIM:619616
Intellectual disability v3.1495 CSNK2B Sarah Leigh Added comment: Comment on phenotypes: Intellectual disability with or without myoclonic epilepsy
Intellectual disability v3.1495 CSNK2B Sarah Leigh Phenotypes for gene: CSNK2B were changed from Intellectual disability with or without myoclonic epilepsy to Poirier-Bienvenu neurodevelopmental syndrome, OMIM:618732; Poirier-Bienvenu neurodevelopmental syndrome, MONDO:0032889
Intellectual disability v3.1494 CSNK2B Sarah Leigh Publications for gene: CSNK2B were set to 28585349; 28762608; 30655572
Early onset or syndromic epilepsy v2.487 CSNK2B Sarah Leigh Phenotypes for gene: CSNK2B were changed from Myoclonic epilepsy and intellectual disability to Poirier-Bienvenu neurodevelopmental syndrome, OMIM:618732; Poirier-Bienvenu neurodevelopmental syndrome, MONDO:0032889
Familial diabetes v1.65 PLIN1 Sarah Leigh edited their review of gene: PLIN1: Added comment: PLIN1 haploinsufficiency is not responsible for the phenotype associated with this gene (PMID:30020498). It would appear that frameshifting variants that escape nonsense-mediated mRNA decay (NMD) are expressed and have a dominant negative effect. At least four frame shifting variants that result in the inclusion of aberrant C-terminal amino acids (125 - 166 amino acids) have been reported in cases of Lipodystrophy, familial partial, type 4 (OMIM:613877) (PMID:21345103;25114292;29747582), together with segregation information in two cases (PMID:21345103). Functional studies show that the variant mRNA is expressed at a lower level than wild type, the variant perilipin was correctly targeted to the lipid-droplet surface, but droplets were smaller than in the wild type cells (PMID:21345103; 25114292).; Changed rating: GREEN; Changed mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Insulin resistance (including lipodystrophy) v1.15 PLIN1 Ivone Leong Mode of pathogenicity for gene: PLIN1 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
Severe insulin resistance and lipodystrophy syndromes v2.19 PLIN1 Arina Puzriakova Mode of pathogenicity for gene: PLIN1 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
Monogenic diabetes v2.46 PLIN1 Ivone Leong Mode of pathogenicity for gene: PLIN1 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
Monogenic diabetes v2.45 PLIN1 Sarah Leigh reviewed gene: PLIN1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Severe insulin resistance and lipodystrophy syndromes v2.18 PLIN1 Sarah Leigh edited their review of gene: PLIN1: Added comment: PLIN1 haploinsufficiency is not responsible for the phenotype associated with this gene (PMID:30020498). It would appear that frameshifting variants that escape nonsense-mediated mRNA decay (NMD) are expressed and have a dominant negative effect. At least four frame shifting variants that result in the inclusion of aberrant C-terminal amino acids (125 - 166 amino acids) have been reported in cases of Lipodystrophy, familial partial, type 4 (OMIM:613877) (PMID:21345103;25114292;29747582), together with segregation information in two cases (PMID:21345103). Functional studies show that the variant mRNA is expressed at a lower level than wild type, the variant perilipin was correctly targeted to the lipid-droplet surface, but droplets were smaller than in the wild type cells (PMID:21345103; 25114292).; Changed rating: GREEN; Changed mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Familial diabetes v1.65 PLIN1 Sarah Leigh Added comment: Comment on phenotypes: partial lipodystrophy, severe dyslipidemia, and insulin-resistant diabetes
Familial diabetes v1.65 PLIN1 Sarah Leigh Phenotypes for gene: PLIN1 were changed from partial lipodystrophy, severe dyslipidemia, and insulin-resistant diabetes to Lipodystrophy, familial partial, type 4, OMIM:613877
Familial diabetes v1.64 PLIN1 Sarah Leigh Publications for gene: PLIN1 were set to 21345103; 30020498; 11371650; 25695774
Severe insulin resistance and lipodystrophy syndromes v2.18 PLIN1 Sarah Leigh Publications for gene: PLIN1 were set to 21345103; 25114292; 30020498; 21757733
Haematological malignancies for rare disease v1.7 NAF1 Arina Puzriakova commented on gene: NAF1
Haematological malignancies cancer susceptibility v2.21 NAF1 Arina Puzriakova commented on gene: NAF1
Monogenic diabetes v2.45 PLIN1 Sarah Leigh Publications for gene: PLIN1 were set to 21345103; 30020498; 11371650; 25695774
Haematological malignancies cancer susceptibility v2.21 NAF1 Arina Puzriakova Tag new-gene-name tag was added to gene: NAF1.
Haematological malignancies for rare disease v1.7 NAF1 Arina Puzriakova Tag new-gene-name tag was added to gene: NAF1.
Multi locus imprinting disorders v0.4 GRB10 Sarah Leigh Classified gene: GRB10 as Green List (high evidence)
Multi locus imprinting disorders v0.4 GRB10 Sarah Leigh Gene: grb10 has been classified as Green List (High Evidence).
Multi locus imprinting disorders v0.3 GRB10 Sarah Leigh edited their review of gene: GRB10: Added comment: Not associated with a phenotype in OMIM, Gen2Phen or MONDO. The imprinted gene, GRB10, has been associated with Silver-Russell syndrome 2, OMIM:618905 in cases with duplication of 7p including GRB10 (PMID: 10631135;12384779;10987657;33187293).; Changed rating: GREEN; Changed publications to: 10631135, 12384779, 10987657, 33187293
Multi locus imprinting disorders v0.3 GRB10 Sarah Leigh Deleted their comment
Multi locus imprinting disorders v0.3 GRB10 Sarah Leigh Phenotypes for gene: GRB10 were changed from Silver-Russell syndrome to Silver-Russell syndrome 2, OMIM:618905
Multi locus imprinting disorders v0.2 GRB10 Sarah Leigh Entity copied from Genomic imprinting v0.117
Multi locus imprinting disorders v0.2 GRB10 Sarah Leigh gene: GRB10 was added
gene: GRB10 was added to Multi locus imprinting disorders. Sources: Literature,Expert Review Amber
Mode of inheritance for gene: GRB10 was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Publications for gene: GRB10 were set to 10861285; 10856193; 27370225; 10856193; 11112662; 30794780; http://igc.otago.ac.nz/home.html
Phenotypes for gene: GRB10 were set to Silver-Russell syndrome
Hereditary haemorrhagic telangiectasia v2.11 GDF2 Eleanor Williams commented on gene: GDF2
Multi locus imprinting disorders v0.1 PLAGL1 Sarah Leigh Entity copied from Genomic imprinting v0.113
Multi locus imprinting disorders v0.1 PLAGL1 Sarah Leigh gene: PLAGL1 was added
gene: PLAGL1 was added to Multi locus imprinting disorders. Sources: Expert Review Green,Literature
Mode of inheritance for gene: PLAGL1 was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Publications for gene: PLAGL1 were set to 16928428; 7719335; 8842729; 11935319; 17084362; 10655556; 30794780; http://igc.otago.ac.nz/home.html
Phenotypes for gene: PLAGL1 were set to {Diabetes mellitus, transient neonatal 1} , OMIM:601410
Familial pulmonary fibrosis v1.22 SFTPB Arina Puzriakova Added comment: Comment on mode of inheritance: Updated MOI from 'monoallelic' to 'biallelic' in line with comments by Helen Savage highlighting there is no evidence of heterozygous variants being associated with disease.
Familial pulmonary fibrosis v1.22 SFTPB Arina Puzriakova Mode of inheritance for gene: SFTPB was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Cholestasis v1.103 HADHA Miranda Durkie reviewed gene: HADHA: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 9003853, 10518281; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cholestasis v1.103 TRMU Miranda Durkie reviewed gene: TRMU: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 23625533, 19732863; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cholestasis v1.103 SMPD1 Miranda Durkie reviewed gene: SMPD1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 27198631, 31811098; Phenotypes: Niemann Pick disease A, Niemann Pick disease B; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Familial pulmonary fibrosis v1.21 HPS4 Arina Puzriakova Publications for gene: HPS4 were set to 11836498, 20301464
Familial pulmonary fibrosis v1.20 HPS1 Arina Puzriakova Publications for gene: HPS1 were set to 8896559, 20301464
Cholestasis v1.103 RINT1 Miranda Durkie reviewed gene: RINT1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31204009; Phenotypes: Infantile liver failure syndrome 3; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cholestasis v1.103 POLG Miranda Durkie reviewed gene: POLG: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20142534, 33720099, 17682973; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Short QT syndrome v2.10 KCNQ1 Sarah Leigh Phenotypes for gene: KCNQ1 were changed from Short QT syndrome 2 609621; Long QT syndrome-1 (192500); Atrial fibrillation, familial, 3 (607554); Short QT syndrome 2 (609621); Idiopathic Ventricular Fibrillation; Short QT-interval syndrome; Jervell and Lange-Nielsen syndrome (220400) to Short QT syndrome 2, OMIM:609621; Long QT syndrome-1, OMIM:192500; Atrial fibrillation, familial, 3, OMIM:607554
Paediatric motor neuronopathies v1.73 SNRPN Sarah Leigh Phenotypes for gene: SNRPN were changed from Prader-Willi syndrome 176270 to Prader-Willi syndrome, OMIM:176270
Retinal disorders v2.242 CTNNA1 Hannah Knight reviewed gene: CTNNA1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 26691986, 33137351; Phenotypes: Macular dystrophy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Retinal disorders v2.242 ARSG Hannah Knight changed review comment from: Multiple reports in the literature of various ARSG mutations causing retinal dystrophy and late-onset hearing loss (referred to as Usher syndrome type 4); to: Multiple reports in the literature of various ARSG mutations causing retinal dystrophy and late-onset hearing loss (referred to as Usher syndrome type 4)
Retinal disorders v2.242 ARSG Hannah Knight reviewed gene: ARSG: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32455177, 33629623, 29300381, 33300174; Phenotypes: Retinal dystrophy, late-onset sensorineural hearing loss; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cholestasis v1.103 MVK Miranda Durkie reviewed gene: MVK: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 9714005, 21425920; Phenotypes: Mevalonate kinase deficiency; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v2.242 RNU4ATAC Hannah Knight gene: RNU4ATAC was added
gene: RNU4ATAC was added to Retinal disorders. Sources: Expert Review,Literature
Mode of inheritance for gene: RNU4ATAC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNU4ATAC were set to PMID: 2801768; 29265708; 30368667
Phenotypes for gene: RNU4ATAC were set to Retinal dystrophy; recurrent bacterial infections; lymphadenopathy; spondyloepiphyseal dysplasia; extreme intrauterine growth retardation; facial dysmorphism; microcephaly; short stature
Penetrance for gene: RNU4ATAC were set to Complete
Review for gene: RNU4ATAC was set to GREEN
Added comment: Noted by OMIM to cause Roifman and Lowry-Wood syndrome, both of which have been associated with retinal dystrophy in the literature
Submitted to PanelApp as we have a patient with Lowry-Wood syndrome and a retinal dystrophy, where we believe we have found two pathogenic variants in RNU4ATAC
Sources: Expert Review, Literature
Structural eye disease v1.101 ZNF408 Nicola Ragge reviewed gene: ZNF408: Rating: RED; Mode of pathogenicity: ; Publications: 30998249; Phenotypes: ; Mode of inheritance:
Structural eye disease v1.101 WRAP73 Nicola Ragge reviewed gene: WRAP73: Rating: RED; Mode of pathogenicity: ; Publications: 33693649; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v1.101 TSC2 Nicola Ragge reviewed gene: TSC2: Rating: AMBER; Mode of pathogenicity: ; Publications: 33110010, 11264130; Phenotypes: Tuberous Sclerosis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v1.101 TBC1D23 Nicola Ragge reviewed gene: TBC1D23: Rating: AMBER; Mode of pathogenicity: ; Publications: 28823707, 28823706; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v1.101 EPHA2 Nicola Ragge edited their review of gene: EPHA2: Added comment: Harding et al. 2021 report two unrelated multi-generation families with microphthalmia and cataract with a missense or splice site variant segregating in affected members. No inheritance for second variant and no data supporting splicing effect. Variants have previously been found in families with cataracts. They also demonstrate that morpholino knockdown of EPHA2b in zebrafish caused microphthalmia. Varsome: missense = VUS; splice variant=pathogenic; Changed rating: AMBER; Changed publications to: 33671840; Changed phenotypes to: Cataract 6, multiple types, Cataract 6, multiple types 116600, 116600
Structural eye disease v1.101 CRYBB3 Nicola Ragge edited their review of gene: CRYBB3: Added comment: congenital/early onset cataract gene, no evidence for involvement in AMC - Zin et al. 2021 report a family with three members affected with paediatric cataract and microphthalmia with a missense variant in CRYBB3. They also refer to Sekeroglu et al. 2020 who described a variant affecting same residue in indiviidual affected by cataract and microphthalmia and his affected mother (cataracts).; Changed rating: AMBER; Changed publications to: 34356085, 33510601; Changed phenotypes to: Cataract 22, autosomal recessive, 609741, Cataract 22, autosomal recessive 609741
Structural eye disease v1.101 BRPF1 Nicola Ragge reviewed gene: BRPF1: Rating: AMBER; Mode of pathogenicity: ; Publications: 33418956, 31176769; Phenotypes: Intellectual developmental disorder with dysmorphic facies and ptosis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v1.101 WLS Nicola Ragge reviewed gene: WLS: Rating: GREEN; Mode of pathogenicity: ; Publications: 34587386, 25715397; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v1.101 TMEM5 Nicola Ragge edited their review of gene: TMEM5: Added comment: Alharbi et al. 2021, 3 families with Walker-Warburg syndrome and homozygous pathogenic TMEM5 variants, with affected individuals in all three families presenting with microphthalmia. No mention of structural eye anomalies in original paper (Vuillaumier-Barrot et al. 2012). Jae et al. 2013 describe 3 families with biallelic pathogenic TMEM5 variants (all parents heterozygous), affected individuals in 2/3 families have microphthalmia.; Changed rating: GREEN; Changed publications to: 33199158, 23217329, 23519211; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v1.101 PACS1 Nicola Ragge reviewed gene: PACS1: Rating: GREEN; Mode of pathogenicity: ; Publications: 34468556, 34068396, 34631081, 29550517, 26842493; Phenotypes: Schuurs-Hoeijmakers syndrome, 615009; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v1.101 HHAT Nicola Ragge reviewed gene: HHAT: Rating: GREEN; Mode of pathogenicity: ; Publications: 33749989, 24784881; Phenotypes: Nivelon-Nivelon-Mabille syndrome 600092; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v1.101 CRIM1 Nicola Ragge edited their review of gene: CRIM1: Added comment: Zhang: mouse model with homozygous hypomorphic allele has cataracts and microphthalmia. Beleggia: one family with Colobomatous macrophthalmia with microcornea syndrome with a het ex15-17 deletion segregating in a large Turkish family. Haug et al. 2021 reported a het partial gene deletion affecting exon 15-17 segregating in three generations of a Portuguese/polish family with coloboma and/or microcornea. The CNVs described in these publications take out the final three exons of CRIM1 but do not involve the coding regions of any other genes. They do not appear to have the same breakpoints, and neither of them is present on DGV or decipher; Changed rating: GREEN; Changed publications to: 26681494, 25561690, 33418956, 26681494, 25561690; Changed phenotypes to: 602499, Macrophthalmia, Colobomatous, with microcornea, Macrophthalmia, Colobomatous, with microcornea 602499
Structural eye disease v1.101 CENPF Nicola Ragge edited their review of gene: CENPF: Added comment: Stromme: two girls with Stromme syndrome and unilateral microcornea, later demonstrated to have compound het truncating variants by Filges, who also described another family with ocular anomalies. Ozkinay: family with two siblings with microphthalmia and Stromme syndrome with homozygous frameshift variant parents het, Alghamdi: family with two siblings with stromme syndrome: one with unilateral microphthalmia and one with corneal opacities with homozygous missense parents het;Syndrome seems mainly cataract - but sometimes with microcornea plus optic nerve coloboma and macular coloboma. Ho et al. 2022 have pubblished a further case with microphthalmia and compound het truncating variants, one inherited from mother; father n/a; Changed publications to: 31953238, 28407396, 26820108, 35001526, 8261651
Structural eye disease v1.101 WDR37 Nicola Ragge edited their review of gene: WDR37: Added comment: Reis et al. 2019 de novo missense variants in four unrelated families with Peter's anomaly, coloboma or microcornea. Hay et al. 2020 de novo missense variants in three unrelated families with syndromic coloboma.; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v1.101 FZD5 Nicola Ragge edited their review of gene: FZD5: Added comment: Liu et al identified a rare heterozygous mutation cosegregating with coloboma. Zebrafish model showing role of gene in the phenotype. Aubert-Mucca et al. 2020: novel variants in three independent families.; Changed publications to: 32737437, 26908622; Changed phenotypes to: None, Coloboma
Structural eye disease v1.101 DYRK1A Nicola Ragge edited their review of gene: DYRK1A: Added comment: Evers et al. 2017 described 3 individuals with coloboma/microphthalmia and de novo variants in DYRK1A among 20 individuals from the DDD study with DYRK1A haploinsufficiency syndrome. Laguna et al found that DYRK1A +/- mice have smaller eyes than their wildtype littermates.; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v1.101 CRYBB1 Nicola Ragge edited their review of gene: CRYBB1: Added comment: Sun: simplex case with cataract coloboma with a rare missense variant. ; Jin et al. 2019 have published large dominant pedigree with cataract and microphthalmia with novel missense variant segregating.Willougby et al. reported a novel stoploss variant segregating in a family with cataract and microcornea.; Changed publications to: 29386872, 31566446, 16110300; Changed phenotypes to: Cataract 17, multiple types, Cataract 17, multiple types 611544, 611544
Structural eye disease v1.101 CDON Nicola Ragge edited their review of gene: CDON: Added comment: Reis et al. 2020: one family with compound het splice variants; Islam et al. 2020 one family with homozygous stopgain variant segregating in parents; Berkun et al. 2019 one family with homozygous stopgain. ; Zhang et al. 2009 demonstrated that Cdo -/- mice have coloboma; Changed publications to: 32729136, 31502381, 19754878
Structural eye disease v1.101 CAPN15 Nicola Ragge edited their review of gene: CAPN15: Added comment: Zha et al. 2020 described 4 families with structural eye anomalies with biallelic variants segregating + animal model. Mor-Shaked et al. 2021 add two siblings with biallelic variant affecting splice donor site and eye abnormalities; Changed publications to: 32885237, 33410501; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v1.101 ASPH Nicola Ragge reviewed gene: ASPH: Rating: GREEN; Mode of pathogenicity: ; Publications: 30194805, 31274573, 31012784, 34018898, 33251883, 24768550; Phenotypes: Traboulsi syndrome 601552; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v1.101 TEK Nicola Ragge reviewed gene: TEK: Rating: GREEN; Mode of pathogenicity: ; Publications: 33027505, 27270174, 34956319, 35011756; Phenotypes: Glaucoma 3, primary congenital, E, OMIM:617272; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v1.101 OCRL Nicola Ragge edited their review of gene: OCRL: Added comment: Yuksel et al 2009. Boy with Lowe syndrome, including microphthalmia and a missense in OCRL1, inheritance not reported. Ma et al. 2020 137 individuals with Lowe syndrome, 79 had molecular confirmation of OCRL1 variant (variants not listed), 41% had developmental glaucoma. Song et al. 2017 2 individuals with Lowe Syndrome and glaucoma with truncating variants inherited from carrier mother (X-linked). Many further reports; Changed rating: GREEN; Changed publications to: 19168822, 32340490, 28473699; Changed phenotypes to: Lowe syndrome 309000, 309000, Lowe syndrome
Structural eye disease v1.101 LMX1B Nicola Ragge edited their review of gene: LMX1B: Added comment: Ghoumid et al. 2016: 9/51 families with LMX1B variants and NPS have glaucoma. There are many other reports.; Changed rating: GREEN; Changed publications to: 25898926; Changed phenotypes to: Nail-patella syndrome, Nail-patella syndrome 161200, 161200
Structural eye disease v1.101 IFIH1 Nicola Ragge reviewed gene: IFIH1: Rating: GREEN; Mode of pathogenicity: ; Publications: 29703882, 31898846; Phenotypes: Aicardi-Goutieres syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v1.101 CREBBP Nicola Ragge reviewed gene: CREBBP: Rating: GREEN; Mode of pathogenicity: ; Publications: 25599811, 11004107, 33629314, 19938080, 21480480; Phenotypes: Rubinstein-Taybi syndrome 1 MIM:180849; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v1.100 ZNF408 Ivone Leong gene: ZNF408 was added
gene: ZNF408 was added to Structural eye disease. Sources: Expert list
Q1_22_NHS_review tags were added to gene: ZNF408.
Mode of inheritance for gene: ZNF408 was set to Unknown
Publications for gene: ZNF408 were set to 30998249
Phenotypes for gene: ZNF408 were set to Retinitis pigmentosa 72, OMIM:616469
Review for gene: ZNF408 was set to RED
Added comment: Sources: Expert list
Structural eye disease v1.99 TSC2 Ivone Leong gene: TSC2 was added
gene: TSC2 was added to Structural eye disease. Sources: Expert list
Q1_22_NHS_review tags were added to gene: TSC2.
Mode of inheritance for gene: TSC2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TSC2 were set to 33110010; 11264130
Phenotypes for gene: TSC2 were set to Tuberous sclerosis-2, OMIM:613254
Review for gene: TSC2 was set to AMBER
Added comment: Sources: Expert list
Structural eye disease v1.98 BRPF1 Ivone Leong gene: BRPF1 was added
gene: BRPF1 was added to Structural eye disease. Sources: Expert list
Q1_22_rating tags were added to gene: BRPF1.
Mode of inheritance for gene: BRPF1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: BRPF1 were set to 33418956; 31176769
Phenotypes for gene: BRPF1 were set to Intellectual developmental disorder with dysmorphic facies and ptosis, OMIM:617333
Review for gene: BRPF1 was set to AMBER
Added comment: Sources: Expert list
Structural eye disease v1.97 WLS Ivone Leong gene: WLS was added
gene: WLS was added to Structural eye disease. Sources: Expert list
Q1_22_NHS_review tags were added to gene: WLS.
Mode of inheritance for gene: WLS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WLS were set to 34587386; 25715397
Phenotypes for gene: WLS were set to Zaki syndrome, OMIM:619648
Review for gene: WLS was set to AMBER
Added comment: Sources: Expert list
Structural eye disease v1.96 PACS1 Ivone Leong gene: PACS1 was added
gene: PACS1 was added to Structural eye disease. Sources: Expert list
Q1_22_NHS_review tags were added to gene: PACS1.
Mode of inheritance for gene: PACS1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PACS1 were set to 29550517; 26842493; 34631081; 34468556; 34068396
Phenotypes for gene: PACS1 were set to Schuurs-Hoeijmakers syndrome, OMIM:615009
Review for gene: PACS1 was set to AMBER
Added comment: Sources: Expert list
Structural eye disease v1.95 HHAT Ivone Leong gene: HHAT was added
gene: HHAT was added to Structural eye disease. Sources: Expert list
Q1_22_NHS_review tags were added to gene: HHAT.
Mode of inheritance for gene: HHAT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HHAT were set to 33749989; 24784881
Phenotypes for gene: HHAT were set to Nivelon-Nivelon-Mabille syndrome, OMIM:600092
Review for gene: HHAT was set to AMBER
Added comment: Sources: Expert list
Severe insulin resistance and lipodystrophy syndromes v2.17 PLIN1 Sarah Leigh Publications for gene: PLIN1 were set to 21345103; 25114292; 30020498
Severe microcephaly v2.277 NCAPD3 Ronnie Wright reviewed gene: NCAPD3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Pancreatitis v2.10 TRPV6 Miranda Durkie changed review comment from: PMID: 31930989: Heterozygous variants that affected function of the TRPV6 protein statistically over represented in cases vs controls (300 cases from Japan, 470 from France, 410 from Germany & >1000 controls). Variants that affected function of the TRPV6 product were found in 13 of 300 patients (4.3%) and 1 of 1070 control individuals (0.1%) from Japan (odds ratio [OR], 48.4; 95% confidence interval [CI], 6.3–371.7; P ¼ 2.4 10–8). Twelve of 124 patients (9.7%) with early-onset CP had such variants. In the replication set from Europe, 18 patients with CP (2.0%) carried variants that affected the function of the TRPV6 product compared with 0 control individuals (P ¼ 6.2 10–8). Homozygous mouse model given cerulein developed more severe pancreatitis than control mice (although homozygous / compound heterozygous disease in humans associated with transient neonatal hyperparathyroidism (OMIM 618188) with no reported pancreatitis). Also reported 20% had trans-heterozygous SPINK1 pathogenic variants.
PMID: 32383311: Chinese case control study of 669 cases and 609 controls showed over represented of confirmed loss of function alleles (9/669 [1.35%] vs. 1/609 [0.16%]; odds ratio = 8.29; p = .022).
Hypothesised treatment with Vitamin D may be beneficial.
Likely susceptibility allele therefore amber rating currently
Sources: Literature

Additional paper: PMID: 34923708 . Sequenced cohort of HCP and ICP and patients and identified 25 novel TRPV6 missense variants. Used functional Ca2+ assay to show 8 are functionally defective. Revealed two novel findings: (i) functionally deficient TRPV6 variants appear to occur more frequently in HCP/FCP patients than in ICP patients (3.2% vs. 1.5%) and (ii) functionally deficient TRPV6 variants found in HCP and FCP probands appear to be more frequently coinherited with known risk variants in SPINK1, CTRC, and/or CFTR than those found in ICP patients (66.7% vs 28.6%). Additionally, genetic analysis of available HCP and FCP family members revealed complex patterns of inheritance in some families. Therefore likely susceptibility allele as part of polygenic model. Keep at amber rating; to: PMID: 31930989: Heterozygous variants that affected function of the TRPV6 protein statistically over represented in cases vs controls (300 cases from Japan, 470 from France, 410 from Germany & >1000 controls). Variants that affected function of the TRPV6 product were found in 13 of 300 patients (4.3%) and 1 of 1070 control individuals (0.1%) from Japan (odds ratio [OR], 48.4; 95% confidence interval [CI], 6.3–371.7; P ¼ 2.4 10–8). Twelve of 124 patients (9.7%) with early-onset CP had such variants. In the replication set from Europe, 18 patients with CP (2.0%) carried variants that affected the function of the TRPV6 product compared with 0 control individuals (P ¼ 6.2 10–8). Homozygous mouse model given cerulein developed more severe pancreatitis than control mice (although homozygous / compound heterozygous disease in humans associated with transient neonatal hyperparathyroidism (OMIM 618188) with no reported pancreatitis). Also reported 20% had trans-heterozygous SPINK1 pathogenic variants.
PMID: 32383311: Chinese case control study of 669 cases and 609 controls showed over represented of confirmed loss of function alleles (9/669 [1.35%] vs. 1/609 [0.16%]; odds ratio = 8.29; p = .022).
Hypothesised treatment with Vitamin D may be beneficial.
Likely susceptibility allele therefore amber rating currently
Sources: Literature

Additional paper: PMID: 34923708 added 20/01/2022. Sequenced cohort of HCP and ICP and patients and identified 25 novel TRPV6 missense variants. Used functional Ca2+ assay to show 8 are functionally defective. Revealed two novel findings: (i) functionally deficient TRPV6 variants appear to occur more frequently in HCP/FCP patients than in ICP patients (3.2% vs. 1.5%) and (ii) functionally deficient TRPV6 variants found in HCP and FCP probands appear to be more frequently coinherited with known risk variants in SPINK1, CTRC, and/or CFTR than those found in ICP patients (66.7% vs 28.6%). Additionally, genetic analysis of available HCP and FCP family members revealed complex patterns of inheritance in some families. Therefore likely susceptibility allele as part of polygenic model. Keep at amber rating 22/01/22
Pancreatitis v2.10 TRPV6 Miranda Durkie changed review comment from: PMID: 31930989: Heterozygous variants that affected function of the TRPV6 protein statistically over represented in cases vs controls (300 cases from Japan, 470 from France, 410 from Germany & >1000 controls). Variants that affected function of the TRPV6 product were found in 13 of 300 patients (4.3%) and 1 of 1070 control individuals (0.1%) from Japan (odds ratio [OR], 48.4; 95% confidence interval [CI], 6.3–371.7; P ¼ 2.4 10–8). Twelve of 124 patients (9.7%) with early-onset CP had such variants. In the replication set from Europe, 18 patients with CP (2.0%) carried variants that affected the function of the TRPV6 product compared with 0 control individuals (P ¼ 6.2 10–8). Homozygous mouse model given cerulein developed more severe pancreatitis than control mice (although homozygous / compound heterozygous disease in humans associated with transient neonatal hyperparathyroidism (OMIM 618188) with no reported pancreatitis). Also reported 20% had trans-heterozygous SPINK1 pathogenic variants.
PMID: 32383311: Chinese case control study of 669 cases and 609 controls showed over represented of confirmed loss of function alleles (9/669 [1.35%] vs. 1/609 [0.16%]; odds ratio = 8.29; p = .022).
Hypothesised treatment with Vitamin D may be beneficial.
Likely susceptibility allele therefore amber rating currently
Sources: Literature; to: PMID: 31930989: Heterozygous variants that affected function of the TRPV6 protein statistically over represented in cases vs controls (300 cases from Japan, 470 from France, 410 from Germany & >1000 controls). Variants that affected function of the TRPV6 product were found in 13 of 300 patients (4.3%) and 1 of 1070 control individuals (0.1%) from Japan (odds ratio [OR], 48.4; 95% confidence interval [CI], 6.3–371.7; P ¼ 2.4 10–8). Twelve of 124 patients (9.7%) with early-onset CP had such variants. In the replication set from Europe, 18 patients with CP (2.0%) carried variants that affected the function of the TRPV6 product compared with 0 control individuals (P ¼ 6.2 10–8). Homozygous mouse model given cerulein developed more severe pancreatitis than control mice (although homozygous / compound heterozygous disease in humans associated with transient neonatal hyperparathyroidism (OMIM 618188) with no reported pancreatitis). Also reported 20% had trans-heterozygous SPINK1 pathogenic variants.
PMID: 32383311: Chinese case control study of 669 cases and 609 controls showed over represented of confirmed loss of function alleles (9/669 [1.35%] vs. 1/609 [0.16%]; odds ratio = 8.29; p = .022).
Hypothesised treatment with Vitamin D may be beneficial.
Likely susceptibility allele therefore amber rating currently
Sources: Literature

Additional paper: PMID: 34923708 . Sequenced cohort of HCP and ICP and patients and identified 25 novel TRPV6 missense variants. Used functional Ca2+ assay to show 8 are functionally defective. Revealed two novel findings: (i) functionally deficient TRPV6 variants appear to occur more frequently in HCP/FCP patients than in ICP patients (3.2% vs. 1.5%) and (ii) functionally deficient TRPV6 variants found in HCP and FCP probands appear to be more frequently coinherited with known risk variants in SPINK1, CTRC, and/or CFTR than those found in ICP patients (66.7% vs 28.6%). Additionally, genetic analysis of available HCP and FCP family members revealed complex patterns of inheritance in some families. Therefore likely susceptibility allele as part of polygenic model. Keep at amber rating
Autoinflammatory disorders v0.32 UBA1 Arina Puzriakova Source NHS GMS was added to UBA1.
Autoinflammatory disorders v0.31 SH3BP2 Arina Puzriakova Source NHS GMS was added to SH3BP2.
Autoinflammatory disorders v0.30 PSMB9 Arina Puzriakova Source NHS GMS was added to PSMB9.
Autoinflammatory disorders v0.29 PSMB4 Arina Puzriakova Source NHS GMS was added to PSMB4.
Autoinflammatory disorders v0.28 TNFRSF1A Arina Puzriakova Source NHS GMS was added to TNFRSF1A.
Autoinflammatory disorders v0.27 TNFAIP3 Arina Puzriakova Source NHS GMS was added to TNFAIP3.
Autoinflammatory disorders v0.26 TMEM173 Arina Puzriakova Source NHS GMS was added to TMEM173.
Autoinflammatory disorders v0.25 SLC29A3 Arina Puzriakova Source NHS GMS was added to SLC29A3.
Autoinflammatory disorders v0.24 RBCK1 Arina Puzriakova Source NHS GMS was added to RBCK1.
Autoinflammatory disorders v0.23 PSTPIP1 Arina Puzriakova Source NHS GMS was added to PSTPIP1.
Autoinflammatory disorders v0.22 PSMB8 Arina Puzriakova Source NHS GMS was added to PSMB8.
Autoinflammatory disorders v0.21 PLCG2 Arina Puzriakova Source NHS GMS was added to PLCG2.
Autoinflammatory disorders v0.20 OTULIN Arina Puzriakova Source NHS GMS was added to OTULIN.
Autoinflammatory disorders v0.19 NOD2 Arina Puzriakova Source NHS GMS was added to NOD2.
Autoinflammatory disorders v0.18 NLRP3 Arina Puzriakova Source NHS GMS was added to NLRP3.
Autoinflammatory disorders v0.17 NLRP12 Arina Puzriakova Source NHS GMS was added to NLRP12.
Autoinflammatory disorders v0.16 NLRC4 Arina Puzriakova Source NHS GMS was added to NLRC4.
Autoinflammatory disorders v0.15 MVK Arina Puzriakova Source NHS GMS was added to MVK.
Autoinflammatory disorders v0.14 MEFV Arina Puzriakova Source NHS GMS was added to MEFV.
Autoinflammatory disorders v0.13 LPIN2 Arina Puzriakova Source NHS GMS was added to LPIN2.
Autoinflammatory disorders v0.12 IL36RN Arina Puzriakova Source NHS GMS was added to IL36RN.
Autoinflammatory disorders v0.11 IL1RN Arina Puzriakova Source NHS GMS was added to IL1RN.
Autoinflammatory disorders v0.10 CARD14 Arina Puzriakova Source NHS GMS was added to CARD14.
Autoinflammatory disorders v0.9 ADA2 Arina Puzriakova Source NHS GMS was added to ADA2.
Malignant hyperthermia v0.4 STAC3 Arina Puzriakova Source NHS GMS was added to STAC3.
Malignant hyperthermia v0.3 RYR1 Arina Puzriakova Source NHS GMS was added to RYR1.
Malignant hyperthermia v0.2 CACNA1S Arina Puzriakova Source NHS GMS was added to CACNA1S.
Acute rhabdomyolysis v0.3 PRKAG2 Arina Puzriakova changed review comment from: RBCK1 is rated Green on the GMS 'Rhabdomyolysis and metabolic muscle disorders panel' (version 1.34) panel. Primarily affects cardiac rather than skeletal muscle. Cannot find reports of rhabdomyolysis.; to: PRKAG2 is rated Green on the GMS 'Rhabdomyolysis and metabolic muscle disorders panel' (version 1.34) panel. Primarily affects cardiac rather than skeletal muscle. Cannot find reports of rhabdomyolysis.
Acute rhabdomyolysis v0.3 SLC2A9 Arina Puzriakova reviewed gene: SLC2A9: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Hypouricemia, renal, 2, OMIM:612076; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Acute rhabdomyolysis v0.3 SLC22A12 Arina Puzriakova reviewed gene: SLC22A12: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Hypouricemia, renal, OMIM:220150; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Acute rhabdomyolysis v0.3 PRKAG2 Arina Puzriakova reviewed gene: PRKAG2: Rating: AMBER; Mode of pathogenicity: ; Publications: 3385534, 16487706; Phenotypes: Glycogen storage disease of heart, lethal congenital, OMIM:261740, Cardiomyopathy, hypertrophic 6, OMIM:600858; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Acute rhabdomyolysis v0.3 PHKG1 Arina Puzriakova reviewed gene: PHKG1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: Unknown
Acute rhabdomyolysis v0.3 CYP2C8 Arina Puzriakova reviewed gene: CYP2C8: Rating: RED; Mode of pathogenicity: ; Publications: 15365880, 20739906; Phenotypes: {Drug metabolism, altered, CYP2C8-related}, OMIM:618018, Rhabdomyolysis, cerivastatin-induced; Mode of inheritance: Unknown
Acute rhabdomyolysis v0.3 COQ8A Arina Puzriakova reviewed gene: COQ8A: Rating: AMBER; Mode of pathogenicity: ; Publications: 26818466, 22036850, 18319074, 18319072; Phenotypes: Coenzyme Q10 deficiency, primary, 4, OMIM:612016; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Acute rhabdomyolysis v0.3 COQ4 Arina Puzriakova reviewed gene: COQ4: Rating: AMBER; Mode of pathogenicity: ; Publications: 28472853, 26185144, 25658047; Phenotypes: Coenzyme Q10 deficiency, primary, 7, OMIM:616276; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Acute rhabdomyolysis v0.3 TYMP Arina Puzriakova reviewed gene: TYMP: Rating: RED; Mode of pathogenicity: ; Publications: 24199812; Phenotypes: Mitochondrial DNA depletion syndrome 1 (MNGIE type), OMIM:603041; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Acute rhabdomyolysis v0.3 TSFM Arina Puzriakova reviewed gene: TSFM: Rating: RED; Mode of pathogenicity: ; Publications: 17033963; Phenotypes: Combined oxidative phosphorylation deficiency 3, OMIM:610505; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Acute rhabdomyolysis v0.3 TSEN54 Arina Puzriakova reviewed gene: TSEN54: Rating: RED; Mode of pathogenicity: ; Publications: 23177318, 25929793; Phenotypes: Pontocerebellar hypoplasia type 2A, OMIM:277470; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Acute rhabdomyolysis v0.3 SUCLA2 Arina Puzriakova reviewed gene: SUCLA2: Rating: AMBER; Mode of pathogenicity: ; Publications: 33231368, 23010432, 17301081; Phenotypes: Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria), OMIM:612073; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Acute rhabdomyolysis v0.3 RRM2B Arina Puzriakova reviewed gene: RRM2B: Rating: AMBER; Mode of pathogenicity: ; Publications: 19138848, 21646632, 19664747; Phenotypes: Mitochondrial DNA depletion syndrome 8A (encephalomyopathic type with renal tubulopathy), OMIM:612075, Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 5, OMIM:613077, Mitochondrial DNA depletion syndrome 8B (MNGIE type), OMIM:612075; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Acute rhabdomyolysis v0.3 RBCK1 Arina Puzriakova reviewed gene: RBCK1: Rating: AMBER; Mode of pathogenicity: ; Publications: 35017290, 23889995, 23798481, 23104095, 25041762; Phenotypes: Polyglucosan body myopathy 1 with or without immunodeficiency, OMIM:615895; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Acute rhabdomyolysis v0.2 TYMP Arina Puzriakova gene: TYMP was added
gene: TYMP was added to Acute rhabdomyolysis. Sources: Expert Review Red,NHS GMS
Mode of inheritance for gene: TYMP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TYMP were set to 24199812
Phenotypes for gene: TYMP were set to Mitochondrial DNA depletion syndrome 1 (MNGIE type), OMIM:603041
Acute rhabdomyolysis v0.2 TSFM Arina Puzriakova gene: TSFM was added
gene: TSFM was added to Acute rhabdomyolysis. Sources: Expert Review Red,NHS GMS
Mode of inheritance for gene: TSFM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TSFM were set to 17033963
Phenotypes for gene: TSFM were set to Combined oxidative phosphorylation deficiency 3, OMIM:610505
Acute rhabdomyolysis v0.2 TSEN54 Arina Puzriakova gene: TSEN54 was added
gene: TSEN54 was added to Acute rhabdomyolysis. Sources: Expert Review Red,NHS GMS
Mode of inheritance for gene: TSEN54 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TSEN54 were set to 25929793; 23177318
Phenotypes for gene: TSEN54 were set to Pontocerebellar hypoplasia type 2A, OMIM:277470
Acute rhabdomyolysis v0.2 TK2 Arina Puzriakova gene: TK2 was added
gene: TK2 was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: TK2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TK2 were set to 29602790; 33457207
Phenotypes for gene: TK2 were set to Mitochondrial DNA depletion syndrome 2 (myopathic type), OMIM:609560
Acute rhabdomyolysis v0.2 TANGO2 Arina Puzriakova gene: TANGO2 was added
gene: TANGO2 was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: TANGO2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TANGO2 were set to 26805782; 30245509; 26805781
Phenotypes for gene: TANGO2 were set to Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration, OMIM:616878
Acute rhabdomyolysis v0.2 SUCLA2 Arina Puzriakova gene: SUCLA2 was added
gene: SUCLA2 was added to Acute rhabdomyolysis. Sources: Expert Review Amber,NHS GMS
Mode of inheritance for gene: SUCLA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SUCLA2 were set to 17301081; 23010432; 33231368
Phenotypes for gene: SUCLA2 were set to Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria), OMIM:612073
Acute rhabdomyolysis v0.2 SLC2A9 Arina Puzriakova gene: SLC2A9 was added
gene: SLC2A9 was added to Acute rhabdomyolysis. Sources: Expert Review Red,NHS GMS
Mode of inheritance for gene: SLC2A9 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: SLC2A9 were set to Hypouricemia, renal, 2, OMIM:612076; Exercise induced kidney injury
Acute rhabdomyolysis v0.2 SLC22A5 Arina Puzriakova gene: SLC22A5 was added
gene: SLC22A5 was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: SLC22A5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC22A5 were set to 29895548
Phenotypes for gene: SLC22A5 were set to Carnitine deficiency, systemic primary, OMIM:212140
Acute rhabdomyolysis v0.2 SLC22A12 Arina Puzriakova gene: SLC22A12 was added
gene: SLC22A12 was added to Acute rhabdomyolysis. Sources: Expert Review Red,NHS GMS
Mode of inheritance for gene: SLC22A12 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC22A12 were set to Exercise induced acute kidney failure; Hypouricemia, renal, OMIM:220150
Acute rhabdomyolysis v0.2 SIL1 Arina Puzriakova gene: SIL1 was added
gene: SIL1 was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: SIL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SIL1 were set to 25929793; 9638664; 11805249
Phenotypes for gene: SIL1 were set to Marinesco-Sjogren syndrome, OMIM:248800
Acute rhabdomyolysis v0.2 SGCA Arina Puzriakova gene: SGCA was added
gene: SGCA was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: SGCA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SGCA were set to 26453141; 23989969; 27297959
Phenotypes for gene: SGCA were set to Muscular dystrophy, limb-girdle, autosomal recessive 3, OMIM:608099
Acute rhabdomyolysis v0.2 SCN4A Arina Puzriakova gene: SCN4A was added
gene: SCN4A was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: SCN4A was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SCN4A were set to 23801527; 28779239; 17998485; 32978841
Phenotypes for gene: SCN4A were set to Exercise induced cramps, muscle fatigue, myopathy; Hyperkalemic periodic paralysis, type 2, OMIM:170500; Hypokalemic periodic paralysis, type 2, OMIM:613345; Paramyotonia congenita, OMIM:168300; Myotonia congenita, atypical, acetazolamide-responsive, OMIM:608390; Myasthenic syndrome, congenital, 16, OMIM:614198
Acute rhabdomyolysis v0.2 RYR1 Arina Puzriakova gene: RYR1 was added
gene: RYR1 was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: RYR1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: RYR1 were set to 34348614; 21514828; 29298851; 33250373; 34414986
Phenotypes for gene: RYR1 were set to {Malignant hyperthermia susceptibility 1}, 145600; Central core disease, OMIM:117000
Acute rhabdomyolysis v0.2 RRM2B Arina Puzriakova gene: RRM2B was added
gene: RRM2B was added to Acute rhabdomyolysis. Sources: Expert Review Amber,NHS GMS
Mode of inheritance for gene: RRM2B was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: RRM2B were set to 19138848; 21646632; 19664747
Phenotypes for gene: RRM2B were set to Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 5, OMIM:613077; Mitochondrial DNA depletion syndrome 8B (MNGIE type), OMIM:612075; Mitochondrial DNA depletion syndrome 8A (encephalomyopathic type with renal tubulopathy), OMIM:612075
Acute rhabdomyolysis v0.2 RBCK1 Arina Puzriakova gene: RBCK1 was added
gene: RBCK1 was added to Acute rhabdomyolysis. Sources: Expert Review Amber,NHS GMS
Mode of inheritance for gene: RBCK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RBCK1 were set to 23798481; 23889995; 23104095; 25041762; 35017290
Phenotypes for gene: RBCK1 were set to Polyglucosan body myopathy 1 with or without immunodeficiency, OMIM:615895
Acute rhabdomyolysis v0.2 PYGM Arina Puzriakova gene: PYGM was added
gene: PYGM was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: PYGM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PYGM were set to 19433441; 25929793; 21880526
Phenotypes for gene: PYGM were set to McArdle disease, OMIM:232600
Acute rhabdomyolysis v0.2 PRKAG2 Arina Puzriakova gene: PRKAG2 was added
gene: PRKAG2 was added to Acute rhabdomyolysis. Sources: Expert Review Amber,NHS GMS
Mode of inheritance for gene: PRKAG2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PRKAG2 were set to 3385534; 16487706
Phenotypes for gene: PRKAG2 were set to Cardiomyopathy, hypertrophic 6, OMIM:600858; Glycogen storage disease of heart, lethal congenital, OMIM:261740
Acute rhabdomyolysis v0.2 POLG2 Arina Puzriakova gene: POLG2 was added
gene: POLG2 was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: POLG2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: POLG2 were set to 21555342; 16685652
Phenotypes for gene: POLG2 were set to Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4, OMIM:610131
Acute rhabdomyolysis v0.2 POLG Arina Puzriakova gene: POLG was added
gene: POLG was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: POLG was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: POLG were set to 25929793; 23873972; 9443501
Phenotypes for gene: POLG were set to Progressive external ophthalmoplegia, autosomal recessive 1, OMIM:258450; Progressive external ophthalmoplegia, autosomal dominant 1, OMIM:157640
Acute rhabdomyolysis v0.2 PHKG1 Arina Puzriakova gene: PHKG1 was added
gene: PHKG1 was added to Acute rhabdomyolysis. Sources: Expert Review Red,NHS GMS
Mode of inheritance for gene: PHKG1 was set to Unknown
Acute rhabdomyolysis v0.2 PHKB Arina Puzriakova gene: PHKB was added
gene: PHKB was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: PHKB was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PHKB were set to Phosphorylase kinase deficiency of liver and muscle, autosomal recessive, OMIM:261750
Acute rhabdomyolysis v0.2 PHKA1 Arina Puzriakova gene: PHKA1 was added
gene: PHKA1 was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: PHKA1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: PHKA1 were set to 25929793
Phenotypes for gene: PHKA1 were set to Muscle glycogenosis, OMIM:300559
Acute rhabdomyolysis v0.2 PGM1 Arina Puzriakova gene: PGM1 was added
gene: PGM1 was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: PGM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PGM1 were set to 25929793; 19625727; 22492991
Phenotypes for gene: PGM1 were set to Congenital disorder of glycosylation, type It, OMIM:614921
Acute rhabdomyolysis v0.2 PGK1 Arina Puzriakova gene: PGK1 was added
gene: PGK1 was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: PGK1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: PGK1 were set to 19157875; 16567715; 1547346; 22348148
Phenotypes for gene: PGK1 were set to Phosphoglycerate kinase 1 deficiency, OMIM:300653
Acute rhabdomyolysis v0.2 PGAM2 Arina Puzriakova gene: PGAM2 was added
gene: PGAM2 was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: PGAM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PGAM2 were set to 25929793; 8447317; 19273759
Phenotypes for gene: PGAM2 were set to Glycogen storage disease X, OMIM:261670
Acute rhabdomyolysis v0.2 PFKM Arina Puzriakova gene: PFKM was added
gene: PFKM was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: PFKM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PFKM were set to 25929793; 11949936; 8037209
Phenotypes for gene: PFKM were set to Glycogen storage disease VII, OMIM:232800
Acute rhabdomyolysis v0.2 OBSCN Arina Puzriakova gene: OBSCN was added
gene: OBSCN was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: OBSCN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OBSCN were set to 34957489
Phenotypes for gene: OBSCN were set to Rhabdomyolysis, myopathy
Acute rhabdomyolysis v0.2 MT-CO2 Arina Puzriakova gene: MT-CO2 was added
gene: MT-CO2 was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene gene: MT-CO2 was set to MITOCHONDRIAL
Publications for gene: MT-CO2 were set to 25929793; 28521807; 14733964; 23616164
Phenotypes for gene: MT-CO2 were set to Cytochrome oxidase deficiency, rhabdomyolysis
Acute rhabdomyolysis v0.2 MT-CO1 Arina Puzriakova gene: MT-CO1 was added
gene: MT-CO1 was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene gene: MT-CO1 was set to MITOCHONDRIAL
Publications for gene: MT-CO1 were set to 25929793; 10980727
Phenotypes for gene: MT-CO1 were set to Leber hereditary optic neuropathy; Myoglobinuria
Acute rhabdomyolysis v0.2 LPIN1 Arina Puzriakova gene: LPIN1 was added
gene: LPIN1 was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: LPIN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LPIN1 were set to 25929793; 18817903; 33514355
Phenotypes for gene: LPIN1 were set to Myoglobinuria, acute recurrent, autosomal recessive, OMIM:268200
Acute rhabdomyolysis v0.2 LDHA Arina Puzriakova gene: LDHA was added
gene: LDHA was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: LDHA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LDHA were set to 1959923; 7449146; 3383424
Phenotypes for gene: LDHA were set to Glycogen storage disease XI, OMIM:612933
Acute rhabdomyolysis v0.2 LAMP2 Arina Puzriakova gene: LAMP2 was added
gene: LAMP2 was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: LAMP2 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: LAMP2 were set to 24222494; 30527948; 27442649
Phenotypes for gene: LAMP2 were set to Danon disease, OMIM:300257
Acute rhabdomyolysis v0.2 ISCU Arina Puzriakova gene: ISCU was added
gene: ISCU was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: ISCU was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ISCU were set to 21165651; 29079705; 22125086
Phenotypes for gene: ISCU were set to Myopathy with lactic acidosis, hereditary, OMIM:255125
Acute rhabdomyolysis v0.2 HADHB Arina Puzriakova gene: HADHB was added
gene: HADHB was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: HADHB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HADHB were set to 25929793; 23868323
Phenotypes for gene: HADHB were set to Trifunctional protein deficiency, OMIM:609015
Acute rhabdomyolysis v0.2 HADHA Arina Puzriakova gene: HADHA was added
gene: HADHA was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: HADHA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HADHA were set to 25929793; 24664533
Phenotypes for gene: HADHA were set to Mitochondrial trifunctional protein deficiency, OMIM:609015
Acute rhabdomyolysis v0.2 GYS1 Arina Puzriakova gene: GYS1 was added
gene: GYS1 was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: GYS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GYS1 were set to 17928598; 19699667; 27604308; 30397902; 21958591; 24579562
Phenotypes for gene: GYS1 were set to Glycogen storage disease 0, muscle, OMIM:611556
Acute rhabdomyolysis v0.2 GYG1 Arina Puzriakova gene: GYG1 was added
gene: GYG1 was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: GYG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GYG1 were set to 27544502; 25272951; 20357282; 26255073; 26652229
Phenotypes for gene: GYG1 were set to Glycogen storage disease XV, OMIM:613507
Acute rhabdomyolysis v0.2 GMPPB Arina Puzriakova gene: GMPPB was added
gene: GMPPB was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: GMPPB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GMPPB were set to 25681410; 23768512; 27874200; 28456886; 26133662
Phenotypes for gene: GMPPB were set to Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 OMIM:615352; Exercise intolerance, myalgia
Acute rhabdomyolysis v0.2 GBE1 Arina Puzriakova gene: GBE1 was added
gene: GBE1 was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: GBE1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GBE1 were set to 20058079; 30397902; 15452297
Phenotypes for gene: GBE1 were set to Glycogen storage disease IV, OMIM:232500
Acute rhabdomyolysis v0.2 GAA Arina Puzriakova gene: GAA was added
gene: GAA was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: GAA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GAA were set to 25929793; 18425781; 14695532
Phenotypes for gene: GAA were set to Glycogen storage disease II, OMIM:232300
Acute rhabdomyolysis v0.2 FLAD1 Arina Puzriakova gene: FLAD1 was added
gene: FLAD1 was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: FLAD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FLAD1 were set to 27259049; 30311138; 28433476
Phenotypes for gene: FLAD1 were set to Lipid storage myopathy due to flavin adenine dinucleotide synthetase deficiency, OMIM:255100
Acute rhabdomyolysis v0.2 FKRP Arina Puzriakova gene: FKRP was added
gene: FKRP was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: FKRP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FKRP were set to 26810512; 21220724; 25929793; 22029705; 32978841
Phenotypes for gene: FKRP were set to Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 5, OMIM:607155
Acute rhabdomyolysis v0.2 FDX2 Arina Puzriakova gene: FDX2 was added
gene: FDX2 was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: FDX2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FDX2 were set to 28803783; 34905296; 30010796; 24281368
Phenotypes for gene: FDX2 were set to Mitochondrial myopathy, episodic, with optic atrophy and reversible leukoencephalopathy, OMIM:251900
Acute rhabdomyolysis v0.2 ETFDH Arina Puzriakova gene: ETFDH was added
gene: ETFDH was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: ETFDH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ETFDH were set to 25929793
Phenotypes for gene: ETFDH were set to Glutaric acidemia IIC, OMIM:231680
Acute rhabdomyolysis v0.2 ETFB Arina Puzriakova gene: ETFB was added
gene: ETFB was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: ETFB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ETFB were set to 25929793; 32550677
Phenotypes for gene: ETFB were set to Glutaric acidemia IIB, OMIM:231680
Acute rhabdomyolysis v0.2 ETFA Arina Puzriakova gene: ETFA was added
gene: ETFA was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: ETFA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ETFA were set to 25929793
Phenotypes for gene: ETFA were set to Glutaric acidemia IIA, OMIM:231680
Acute rhabdomyolysis v0.2 ENO3 Arina Puzriakova gene: ENO3 was added
gene: ENO3 was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: ENO3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ENO3 were set to 25267339; 11506403; 25929793; 31741825
Phenotypes for gene: ENO3 were set to Exercise induced rhabdomyolysis; Glycogen storage disease XIII, OMIM:612932
Acute rhabdomyolysis v0.2 DYSF Arina Puzriakova gene: DYSF was added
gene: DYSF was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: DYSF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DYSF were set to 17287450; 18306167; 15477515
Phenotypes for gene: DYSF were set to Miyoshi muscular dystrophy 1, OMIM:254130; Myopathy, distal, with anterior tibial onset, OMIM:606768; Muscular dystrophy, limb-girdle, autosomal recessive 2, OMIM:253601
Acute rhabdomyolysis v0.2 DMD Arina Puzriakova gene: DMD was added
gene: DMD was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: DMD was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: DMD were set to 1822795; 19396825
Phenotypes for gene: DMD were set to Becker muscular dystrophy, OMIM:300376; Exercise induced crams and myoglobinuria
Acute rhabdomyolysis v0.2 DGUOK Arina Puzriakova gene: DGUOK was added
gene: DGUOK was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: DGUOK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DGUOK were set to 23043144
Phenotypes for gene: DGUOK were set to Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 4, OMIM:617070
Acute rhabdomyolysis v0.2 CYP2C8 Arina Puzriakova gene: CYP2C8 was added
gene: CYP2C8 was added to Acute rhabdomyolysis. Sources: Expert Review Red,NHS GMS
Mode of inheritance for gene: CYP2C8 was set to Unknown
Publications for gene: CYP2C8 were set to 20739906; 15365880
Phenotypes for gene: CYP2C8 were set to Rhabdomyolysis, cerivastatin-induced; {Drug metabolism, altered, CYP2C8-related}, OMIM:618018
Acute rhabdomyolysis v0.2 CPT2 Arina Puzriakova gene: CPT2 was added
gene: CPT2 was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: CPT2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: CPT2 were set to 11994355; 23911907; 10873395; 15622536; 21913903; 24843804; 23184072
Phenotypes for gene: CPT2 were set to Exercise intolerance and rhabdomyolysis, late onset; CPT II deficiency, myopathic, stress-induced, OMIM:255110
Acute rhabdomyolysis v0.2 COQ8A Arina Puzriakova gene: COQ8A was added
gene: COQ8A was added to Acute rhabdomyolysis. Sources: Expert Review Amber,NHS GMS
Mode of inheritance for gene: COQ8A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COQ8A were set to 18319072; 22036850; 26818466; 18319074
Phenotypes for gene: COQ8A were set to Coenzyme Q10 deficiency, primary, 4, OMIM:612016
Acute rhabdomyolysis v0.2 COQ4 Arina Puzriakova gene: COQ4 was added
gene: COQ4 was added to Acute rhabdomyolysis. Sources: Expert Review Amber,NHS GMS
Mode of inheritance for gene: COQ4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COQ4 were set to 26185144; 25658047; 28472853
Phenotypes for gene: COQ4 were set to Rhabdomyolysis; Coenzyme Q10 deficiency, primary, 7, OMIM:616276
Acute rhabdomyolysis v0.2 CHKB Arina Puzriakova gene: CHKB was added
gene: CHKB was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: CHKB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHKB were set to 25187204; 23692895; 21665002; 26782016
Phenotypes for gene: CHKB were set to Muscular dystrophy, congenital, megaconial type, OMIM:602541
Acute rhabdomyolysis v0.2 CAV3 Arina Puzriakova gene: CAV3 was added
gene: CAV3 was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: CAV3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CAV3 were set to 12666119; 15668980; 11251997; 27312022; 16730439; 9536092
Phenotypes for gene: CAV3 were set to Rippling muscle disease, OMIM:606072; Myopathy, distal, Tateyama type, OMIM:614321
Acute rhabdomyolysis v0.2 CACNA1S Arina Puzriakova gene: CACNA1S was added
gene: CACNA1S was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: CACNA1S was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CACNA1S were set to 28011884; 19825159; 29193480; 25735680
Phenotypes for gene: CACNA1S were set to {Malignant hyperthermia susceptibility 5}, OMIM:601887
Acute rhabdomyolysis v0.2 ANO5 Arina Puzriakova gene: ANO5 was added
gene: ANO5 was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: ANO5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ANO5 were set to 25929793
Phenotypes for gene: ANO5 were set to Muscular dystrophy, limb-girdle, autosomal recessive 12, OMIM:611307; Miyoshi muscular dystrophy 3, OMIM:613319
Acute rhabdomyolysis v0.2 AMPD1 Arina Puzriakova gene: AMPD1 was added
gene: AMPD1 was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: AMPD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AMPD1 were set to 19258857; 15803807; 25929793; 11331279; 23543093
Phenotypes for gene: AMPD1 were set to Myopathy due to myoadenylate deaminase deficiency, OMIM:615511
Acute rhabdomyolysis v0.2 ALDOA Arina Puzriakova gene: ALDOA was added
gene: ALDOA was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: ALDOA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALDOA were set to 2825199; 25929793; 14615364; 8598869; 25392908
Phenotypes for gene: ALDOA were set to Glycogen storage disease XII, OMIM:611881
Acute rhabdomyolysis v0.2 AGL Arina Puzriakova gene: AGL was added
gene: AGL was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: AGL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AGL were set to 25929793; 20648714
Phenotypes for gene: AGL were set to Glycogen storage disease IIIb, OMIM:232400; Glycogen storage disease IIIa, OMIM:232400
Acute rhabdomyolysis v0.2 ACADVL Arina Puzriakova gene: ACADVL was added
gene: ACADVL was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: ACADVL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACADVL were set to 25929793; 9973285; 8739957
Phenotypes for gene: ACADVL were set to VLCAD deficiency, OMIM:201475
Acute rhabdomyolysis v0.2 ACADM Arina Puzriakova gene: ACADM was added
gene: ACADM was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: ACADM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACADM were set to 27856190; 11409868
Phenotypes for gene: ACADM were set to Acyl-CoA dehydrogenase, medium chain, deficiency of, OMIM:201450
Acute rhabdomyolysis v0.2 ACAD9 Arina Puzriakova gene: ACAD9 was added
gene: ACAD9 was added to Acute rhabdomyolysis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: ACAD9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACAD9 were set to 17564966; 23836383
Phenotypes for gene: ACAD9 were set to Mitochondrial complex I deficiency, nuclear type 20, OMIM:611126
Acute rhabdomyolysis v0.0 Arina Puzriakova Added Panel Acute rhabdomyolysis
Set panel types to: GMS Rare Disease
Cholestasis v1.103 NBAS Ivone Leong Phenotypes for gene: NBAS were changed from Infantile liver failure syndrome 2, 616483 to Infantile liver failure syndrome 2, OMIM:616483
Cholestasis v1.102 GBE1 Ivone Leong Publications for gene: GBE1 were set to 8613547
Cholestasis v1.101 GALK1 Ivone Leong Publications for gene: GALK1 were set to
Renal tubulopathies v2.30 SEC61A1 Detlef Bockenhauer gene: SEC61A1 was added
gene: SEC61A1 was added to Renal tubulopathies. Sources: Literature
Mode of inheritance for gene: SEC61A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SEC61A1 were set to PMID: 33185949; 27392076; 31488840
Phenotypes for gene: SEC61A1 were set to hyporeninaemic hypoaldosteronism; autosomal dominant tubulointerstitial kidney disease
Penetrance for gene: SEC61A1 were set to Complete
Review for gene: SEC61A1 was set to GREEN
Added comment: very few patients/families reported so far, so "green" status should be reviewed carefully
Sources: Literature
Multi locus imprinting disorders v0.0 Sarah Leigh Added Panel Multi locus imprinting disorders
Set panel types to: GMS Rare Disease
COVID-19 research v1.114 KIR2DL2 Eleanor Williams changed review comment from: Ensembl identifier not available for GRCh38 (release 90). On GRCh it is on a patch chromosome so chromosome location not added.; to: Ensembl identifier not available for GRCh38 (release 90). On GRCh37 it is on a patch chromosome so chromosome location not added.
Cholestasis v1.100 GBE1 Miranda Durkie reviewed gene: GBE1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 20301758; Phenotypes: Polyglucosan body disease, adult form; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cholestasis v1.100 NBAS Miranda Durkie reviewed gene: NBAS: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31761904; Phenotypes: Infantile liver failure syndrome 2; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cholestasis v1.100 GALK1 Miranda Durkie reviewed gene: GALK1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 33413482, PMID: 28108845; Phenotypes: Galactokinase deficiency with cataracts; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cholestasis v1.100 GALE Miranda Durkie reviewed gene: GALE: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 21290786; Phenotypes: Epimerase deficiency galactosemia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rhabdomyolysis and metabolic muscle disorders v1.75 TSEN54 Arina Puzriakova changed review comment from: Literature search showed that rhabdomyolysis has been identified in 6 PCH-2 patients (PMIDs: 17825555; 23177318); however, only one of these individuals has a confirmed variant in TSEN54 (PMID: 23177318). Subsequent reports describing >50 individuals with TSEN54-related PCH do not provide any evidence of rhabdomyolysis in these cases (PMIDs: 20956791; 20952379).; to: Literature search showed that rhabdomyolysis has been identified in 3 PCH-2 patients (PMIDs: 17825555; 23177318); however, only one of these individuals was genetically confirmed with variants in TSEN54 (PMID: 23177318). Subsequent reports describing >50 individuals with TSEN54-related PCH do not provide any evidence of rhabdomyolysis in these cases (PMIDs: 20956791; 20952379).
Osteogenesis imperfecta v2.37 MBTPS2 Michael Oldridge reviewed gene: MBTPS2: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 34093655; Phenotypes: OI type XIX OMIM301014; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Skeletal dysplasia v2.168 BMP2 Jenny Simmonds reviewed gene: BMP2: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 21357617, 29129813, 24710560, 19327734; Phenotypes: Brachydactyly, type A2; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Limb disorders v2.65 BMP2 Jenny Simmonds reviewed gene: BMP2: Rating: GREEN; Mode of pathogenicity: None; Publications: (PMID: 21357617, 29129813, 24710560, 19327734); Phenotypes: Brachydactyly, type A2; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rhabdomyolysis and metabolic muscle disorders v1.75 PRKAG2 Arina Puzriakova commented on gene: PRKAG2
Rhabdomyolysis and metabolic muscle disorders v1.75 TYMP Arina Puzriakova commented on gene: TYMP
Rhabdomyolysis and metabolic muscle disorders v1.75 TYMP Arina Puzriakova Phenotypes for gene: TYMP were changed from Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria) 612073 to Mitochondrial DNA depletion syndrome 1 (MNGIE type), OMIM:603041
Rhabdomyolysis and metabolic muscle disorders v1.74 TSFM Arina Puzriakova commented on gene: TSFM
Skeletal dysplasia v2.168 DSPP Michael Oldridge changed review comment from: agree should be demoted to Red.
Dentinogenesis imperfecta appears to only affect the teeth, no evidence of OI phenotype in these cases.; to: agree should be demoted to Red.
Dentinogenesis imperfecta appears to only affect the teeth, no evidence of OI phenotype in reported cases.
Skeletal dysplasia v2.168 DSPP Michael Oldridge reviewed gene: DSPP: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Dentinogenesis imperfecta; Mode of inheritance: None
Rhabdomyolysis and metabolic muscle disorders v1.74 SGCA Arina Puzriakova Classified gene: SGCA as Amber List (moderate evidence)
Rhabdomyolysis and metabolic muscle disorders v1.74 SGCA Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark. Rhabdomyolysis has been reported as a presenting feature in some cases including muscle weakness, exercise intolerance, myalgia, myoglobinuria, and hyperCKemia. Sufficient unrelated cases (>3) in literature to promote this gene to Green at the next GMS review.
Rhabdomyolysis and metabolic muscle disorders v1.74 SGCA Arina Puzriakova Gene: sgca has been classified as Amber List (Moderate Evidence).
Rhabdomyolysis and metabolic muscle disorders v1.73 SGCA Arina Puzriakova Tag Q1_22_rating tag was added to gene: SGCA.
Rhabdomyolysis and metabolic muscle disorders v1.73 SGCA Arina Puzriakova Phenotypes for gene: SGCA were changed from Muscular dystrophy, limb-girdle, autosomal recessive 3 MIM#608099 to Muscular dystrophy, limb-girdle, autosomal recessive 3, OMIM:608099
Rhabdomyolysis and metabolic muscle disorders v1.72 SCN4A Arina Puzriakova Tag Q1_22_rating tag was added to gene: SCN4A.
Rhabdomyolysis and metabolic muscle disorders v1.72 SCN4A Arina Puzriakova Classified gene: SCN4A as Amber List (moderate evidence)
Rhabdomyolysis and metabolic muscle disorders v1.72 SCN4A Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark. Rhabdomyolysis has been reported as a presenting feature in some cases of SCN4A-related muscle disorders. Sufficient unrelated cases (>3) in literature to promote this gene to Green at the next GMS review.
Rhabdomyolysis and metabolic muscle disorders v1.72 SCN4A Arina Puzriakova Gene: scn4a has been classified as Amber List (Moderate Evidence).
Rhabdomyolysis and metabolic muscle disorders v1.71 POLG Arina Puzriakova Phenotypes for gene: POLG were changed from Mitochondrial DNA depletion syndrome 4A (Alpers type) 203700; Mitochondrial DNA depletion syndrome 4B (MNGIE type) 613662; Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE) 607459; Progressive external ophthalmoplegia, autosomal dominant 1 157640; Progressive external ophthalmoplegia, autosomal recessive 1 258450 to Progressive external ophthalmoplegia, autosomal dominant 1, OMIM:157640; Progressive external ophthalmoplegia, autosomal recessive 1, OMIM:258450
Hereditary neuropathy or pain disorder v1.80 SLC5A6 Ian Berry gene: SLC5A6 was added
gene: SLC5A6 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: NHS GMS
Mode of inheritance for gene: SLC5A6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC5A6 were set to PMID: 35013551
Phenotypes for gene: SLC5A6 were set to motor neuropathy
Penetrance for gene: SLC5A6 were set to Complete
Review for gene: SLC5A6 was set to GREEN
Added comment: Five individuals reported including three siblings with identical genotypes. Targeted therapy with biotin (therapeutic in other manifestations of this gene and in other biotin transporter deficiencies) improved phenotype in patients.
Sources: NHS GMS
Familial pulmonary fibrosis v1.19 AP3B1 Arina Puzriakova Publications for gene: AP3B1 were set to 10024875, 20301464
Rhabdomyolysis and metabolic muscle disorders v1.70 HADHA Arina Puzriakova Phenotypes for gene: HADHA were changed from Trifunctional protein deficiency 609015 to Mitochondrial trifunctional protein deficiency, OMIM:609015
Rhabdomyolysis and metabolic muscle disorders v1.69 GYS1 Arina Puzriakova Phenotypes for gene: GYS1 were changed from Glycogen storage disease 0, muscle 611556 to Glycogen storage disease 0, muscle, OMIM:611556
Rhabdomyolysis and metabolic muscle disorders v1.68 ENO3 Arina Puzriakova Phenotypes for gene: ENO3 were changed from ?Glycogen storage disease XIII 612932 to Glycogen storage disease XIII, OMIM:612932
Rhabdomyolysis and metabolic muscle disorders v1.67 DYSF Arina Puzriakova Phenotypes for gene: DYSF were changed from Miyoshi muscular dystrophy 1 254130; Muscular dystrophy, limb-girdle, type 2B 253601; Myopathy, distal, with anterior tibial onset 606768 to Miyoshi muscular dystrophy 1, OMIM:254130; Muscular dystrophy, limb-girdle, autosomal recessive 2, OMIM:253601; Myopathy, distal, with anterior tibial onset, OMIM:606768
Rhabdomyolysis and metabolic muscle disorders v1.66 CYP2C8 Arina Puzriakova Phenotypes for gene: CYP2C8 were changed from Rhabdomyolysis, cerivastatin-induced to {Drug metabolism, altered, CYP2C8-related}, OMIM:618018; Rhabdomyolysis, cerivastatin-induced
Rare syndromic craniosynostosis or isolated multisuture synostosis v2.61 ZNF462 Eleanor Williams commented on gene: ZNF462: Helen Lord review concurs with proposed green rating.
Rare syndromic craniosynostosis or isolated multisuture synostosis v2.61 ZNF462 Eleanor Williams Tag Q1_22_NHS_review tag was added to gene: ZNF462.
Likely inborn error of metabolism v2.221 CPT2 Arina Puzriakova Tag Q1_22_MOI tag was added to gene: CPT2.
Undiagnosed metabolic disorders v1.508 CPT2 Arina Puzriakova Added comment: Comment on mode of inheritance: MOI was updated from 'Biallelic' to 'Both mono- and biallelic'. Although most cases are associated with biallelic variants, symptomatic heterozygous patients have also been described (PMID: 15622536; 21913903; 23184072; 24843804). Severity of symptoms tends to correlate with residual CPT enzyme activity but it is plausible that heterozygotes may still be tested under this panel. Both MOIs are listed in OMIM for this phenotype (MIM# 255110)
Undiagnosed metabolic disorders v1.508 CPT2 Arina Puzriakova Mode of inheritance for gene: CPT2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Likely inborn error of metabolism v2.221 CPT2 Arina Puzriakova Added comment: Comment on mode of inheritance: MOI should be updated from 'Biallelic' to 'Both mono- and biallelic' at the next GMS review. Although most cases are associated with biallelic variants, symptomatic heterozygous patients have also been described (PMID: 15622536; 21913903; 23184072; 24843804). Severity of symptoms tends to correlate with residual CPT enzyme activity but it is plausible that heterozygotes may still be tested under this panel. Both MOIs are listed in OMIM for this phenotype (MIM# 255110)
Likely inborn error of metabolism v2.221 CPT2 Arina Puzriakova Mode of inheritance for gene: CPT2 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v2.220 CPT2 Arina Puzriakova Publications for gene: CPT2 were set to 27604308; 24816252
Undiagnosed metabolic disorders v1.507 CPT2 Arina Puzriakova Publications for gene: CPT2 were set to 27604308; 24816252
Rhabdomyolysis and metabolic muscle disorders v1.65 CPT2 Arina Puzriakova Publications for gene: CPT2 were set to 25929793; 23911907; 10873395
Rhabdomyolysis and metabolic muscle disorders v1.64 CPT2 Arina Puzriakova Tag Q1_22_MOI tag was added to gene: CPT2.
Rhabdomyolysis and metabolic muscle disorders v1.64 CPT2 Arina Puzriakova Added comment: Comment on mode of inheritance: MOI should be updated from 'Biallelic' to 'Both mono- and biallelic' at the next GMS review. Although most cases are associated with biallelic variants, symptomatic heterozygous patients have also been described (PMID: 15622536; 21913903; 23184072; 24843804). Severity of symptoms tends to correlate with residual CPT enzyme activity but it is plausible that heterozygotes may still be tested under this panel. Both MOIs are listed in OMIM for this phenotype (MIM# 255110)
Rhabdomyolysis and metabolic muscle disorders v1.64 CPT2 Arina Puzriakova Mode of inheritance for gene: CPT2 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Rhabdomyolysis and metabolic muscle disorders v1.63 CPT2 Arina Puzriakova Phenotypes for gene: CPT2 were changed from CPT II deficiency, myopathic, stress-induced (exercise intolerance and rhabdomyolysis, late onset) 255110 to CPT II deficiency, myopathic, stress-induced, OMIM:255110; Exercise intolerance and rhabdomyolysis, late onset
Likely inborn error of metabolism v2.219 CPT2 Arina Puzriakova Phenotypes for gene: CPT2 were changed from CPT deficiency, hepatic, type II 600649; CPT II deficiency, lethal neonatal 608836; Carnitine palmitoyltransferase II (CPTII) deficiency (Disorders of carnitine transport and the carnitine cycle) to CPT II deficiency, infantile, OMIM:600649; CPT II deficiency, lethal neonatal, OMIM:608836; CPT II deficiency, myopathic, stress-induced, OMIM:255110; Carnitine palmitoyltransferase II (CPTII) deficiency (Disorders of carnitine transport and the carnitine cycle)
Undiagnosed metabolic disorders v1.506 CPT2 Arina Puzriakova Phenotypes for gene: CPT2 were changed from Carnitine palmitoyltransferase II (CPTII) deficiency (Disorders of carnitine transport and the carnitine cycle); CPT deficiency, hepatic, type II 600649; CPT II deficiency, lethal neonatal 608836 to CPT II deficiency, infantile, OMIM:600649; CPT II deficiency, lethal neonatal, OMIM:608836; CPT II deficiency, myopathic, stress-induced, OMIM:255110; Carnitine palmitoyltransferase II (CPTII) deficiency (Disorders of carnitine transport and the carnitine cycle)
Paediatric or syndromic cardiomyopathy v1.60 CPT2 Arina Puzriakova Phenotypes for gene: CPT2 were changed from DCM; Carnitine palmitoyltransferase II (CPTII) deficiency (Disorders of carnitine transport and the carnitine cycle); Carnitine palmitoyltransferase II (CPT2) deficiency (neonatal & infantile forms); HCM, mixed; Arrhythmia, liver disease, hyperammonaemia, hypoketotic hypoglycaemia; CPT II deficiency, lethal neonatal 608836; CPT deficiency, hepatic, type II 600649 to CPT II deficiency, infantile, OMIM:600649; CPT II deficiency, lethal neonatal, OMIM:608836; CPT II deficiency, myopathic, stress-induced, OMIM:255110
Mitochondrial disorders v2.85 CPT2 Arina Puzriakova Phenotypes for gene: CPT2 were changed from CPT II deficiency, myopathic, stress-induced, 255110 to CPT II deficiency, infantile, OMIM:600649; CPT II deficiency, lethal neonatal, OMIM:608836; CPT II deficiency, myopathic, stress-induced, OMIM:255110
Possible mitochondrial disorder - nuclear genes v1.64 CPT2 Arina Puzriakova Phenotypes for gene: CPT2 were changed from CPT II deficiency, myopathic, stress-induced, 255110 to CPT II deficiency, infantile, OMIM:600649; CPT II deficiency, lethal neonatal, OMIM:608836; CPT II deficiency, myopathic, stress-induced, OMIM:255110
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v2.33 CPT2 Arina Puzriakova Phenotypes for gene: CPT2 were changed from CPT II deficiency, infantile, 600649; metabolic myopathy to CPT II deficiency, infantile, OMIM:600649; CPT II deficiency, lethal neonatal, OMIM:608836
Fetal anomalies v1.826 CPT2 Arina Puzriakova Phenotypes for gene: CPT2 were changed from CPT deficiency, hepatic, type II 600649; CPT II deficiency, lethal neonatal 608836; Myopathy due to CPT II deficiency 255110 to CPT II deficiency, infantile, OMIM:600649; CPT II deficiency, lethal neonatal, OMIM:608836
Congenital myopathy v2.70 CPT2 Arina Puzriakova Phenotypes for gene: CPT2 were changed from CPT II deficiency, infantile 600649; CPT II deficiency, lethal neonatal 608836; CPT II deficiency, myopathic, stress-induced 255110 to CPT II deficiency, infantile, OMIM:600649; CPT II deficiency, lethal neonatal, OMIM:608836
Arthrogryposis v3.147 CPT2 Arina Puzriakova Phenotypes for gene: CPT2 were changed from Myopathy due to CPT II deficiency, 255110 to CPT II deficiency, infantile, OMIM:600649; CPT II deficiency, lethal neonatal, OMIM:608836
Ductal plate malformation v1.19 CPT2 Arina Puzriakova Phenotypes for gene: CPT2 were changed from CPT II deficiency, infantile (600649); CPT II deficiency, lethal neonatal (608836) to CPT II deficiency, infantile, OMIM:600649; CPT II deficiency, lethal neonatal, OMIM:608836
Hyperammonaemia v1.13 CPT2 Arina Puzriakova Phenotypes for gene: CPT2 were changed from CPT deficiency, hepatic, type II 600649; CPT II deficiency, lethal neonatal 608836 to CPT II deficiency, infantile, OMIM:600649; CPT II deficiency, lethal neonatal, OMIM:608836
Rare syndromic craniosynostosis or isolated multisuture synostosis v2.61 HNRNPK Eleanor Williams Tag Q1_22_NHS_review tag was added to gene: HNRNPK.
Rare syndromic craniosynostosis or isolated multisuture synostosis v2.61 LTBP1 Eleanor Williams commented on gene: LTBP1: Helen Lord's review concurs with the recommendation to rate this gene green.
Rare syndromic craniosynostosis or isolated multisuture synostosis v2.61 LTBP1 Eleanor Williams Tag Q1_22_NHS_review tag was added to gene: LTBP1.
Cystic kidney disease v2.31 IFT140 Anna de Burca reviewed gene: IFT140: Rating: GREEN; Mode of pathogenicity: None; Publications: 34890546; Phenotypes: Autosomal dominant polycystic kidney disease; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rhabdomyolysis and metabolic muscle disorders v1.62 ALDOA Arina Puzriakova Phenotypes for gene: ALDOA were changed from Glycogen storage disease XII 611881 to Glycogen storage disease XII, OMIM:611881
Rhabdomyolysis and metabolic muscle disorders v1.61 ACADVL Arina Puzriakova Phenotypes for gene: ACADVL were changed from VLCAD deficiency 201475 to VLCAD deficiency, OMIM:201475
Unexplained young onset end-stage renal disease v1.27 XPNPEP3 Sarah Leigh Tag Q1_22_rating tag was added to gene: XPNPEP3.
Unexplained young onset end-stage renal disease v1.27 XPNPEP3 Sarah Leigh edited their review of gene: XPNPEP3: Added comment: Associated with relevant phenotype in OMIM and as limited Gen2Phen gene. At least three variants were reported in three unrelated cases (PMID: 32660933; 20179356). Two of the variants were terminating (RCV000000069, RCV001554332) and the third was a missense variant (RCV000000068), that seems to activate a cryptic splice site; RT-PCR of lymphoblastoid cells showed that this resulted in the inclusion of intronic bases and a frameshift. Cilia-related function was examined by the suppression of zebrafish xpnpep3, resulting in phenotypes reminiscent of ciliopathy morphants, this effect was rescued by human XPNPEP3 that was devoid of a mitochondrial localization signal (PMID: 20179356).; Changed rating: GREEN
Likely inborn error of metabolism v2.218 XPNPEP3 Sarah Leigh edited their review of gene: XPNPEP3: Added comment: Associated with relevant phenotype in OMIM and as limited Gen2Phen gene. At least three variants were reported in three unrelated cases (PMID: 32660933; 20179356). Two of the variants were terminating (RCV000000069, RCV001554332) and the third was a missense variant (RCV000000068), that seems to activate a cryptic splice site; RT-PCR of lymphoblastoid cells showed that this resulted in the inclusion of intronic bases and a frameshift. Cilia-related function was examined by the suppression of zebrafish xpnpep3, resulting in phenotypes reminiscent of ciliopathy morphants, this effect was rescued by human XPNPEP3 that was devoid of a mitochondrial localization signal (PMID: 20179356).; Changed rating: GREEN
Likely inborn error of metabolism v2.218 XPNPEP3 Sarah Leigh Tag Q1_22_rating tag was added to gene: XPNPEP3.
Cystic kidney disease v2.31 XPNPEP3 Sarah Leigh edited their review of gene: XPNPEP3: Added comment: Associated with relevant phenotype in OMIM and as limited Gen2Phen gene. At least three variants were reported in three unrelated cases (PMID: 32660933; 20179356). Two of the variants were terminating (RCV000000069, RCV001554332) and the third was a missense variant (RCV000000068), that seems to activate a cryptic splice site; RT-PCR of lymphoblastoid cells showed that this resulted in the inclusion of intronic bases and a frameshift. Cilia-related function was examined by the suppression of zebrafish xpnpep3, resulting in phenotypes reminiscent of ciliopathy morphants, this effect was rescued by human XPNPEP3 that was devoid of a mitochondrial localization signal (PMID: 20179356).; Changed rating: GREEN
Tubulointerstitial kidney disease v1.14 XPNPEP3 Sarah Leigh Tag Q1_22_rating tag was added to gene: XPNPEP3.
Tubulointerstitial kidney disease v1.14 XPNPEP3 Sarah Leigh edited their review of gene: XPNPEP3: Added comment: Associated with relevant phenotype in OMIM and as limited Gen2Phen gene. At least three variants were reported in three unrelated cases (PMID: 32660933; 20179356). Two of the variants were terminating (RCV000000069, RCV001554332) and the third was a missense variant (RCV000000068), that seems to activate a cryptic splice site; RT-PCR of lymphoblastoid cells showed that this resulted in the inclusion of intronic bases and a frameshift. Cilia-related function was examined by the suppression of zebrafish xpnpep3, resulting in phenotypes reminiscent of ciliopathy morphants, this effect was rescued by human XPNPEP3 that was devoid of a mitochondrial localization signal (PMID: 20179356); Changed rating: GREEN
Mitochondrial disorders v2.84 XPNPEP3 Sarah Leigh Deleted their comment
Unexplained kidney failure in young people v1.104 XPNPEP3 Sarah Leigh Classified gene: XPNPEP3 as Green List (high evidence)
Unexplained kidney failure in young people v1.104 XPNPEP3 Sarah Leigh Gene: xpnpep3 has been classified as Green List (High Evidence).
Unexplained kidney failure in young people v1.103 XPNPEP3 Sarah Leigh Deleted their comment
Intellectual disability v3.1493 XPNPEP3 Sarah Leigh reviewed gene: XPNPEP3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
DDG2P v2.60 XPNPEP3 Sarah Leigh Tag Q1_22_rating tag was added to gene: XPNPEP3.
DDG2P v2.60 XPNPEP3 Sarah Leigh edited their review of gene: XPNPEP3: Added comment: Associated with relevant phenotype in OMIM and as limited Gen2Phen gene. At least three variants were reported in three unrelated cases (PMID: 32660933; 20179356). Two of the variants were terminating (RCV000000069, RCV001554332) and the third was a missense variant (RCV000000068), that seems to activate a cryptic splice site; RT-PCR of lymphoblastoid cells showed that this resulted in the inclusion of intronic bases and a frameshift. Cilia-related function was examined by the suppression of zebrafish xpnpep3, resulting in phenotypes reminiscent of ciliopathy morphants, this effect was rescued by human XPNPEP3 that was devoid of a mitochondrial localization signal (PMID: 20179356).; Changed rating: GREEN
Rare multisystem ciliopathy disorders v1.157 XPNPEP3 Sarah Leigh Classified gene: XPNPEP3 as Red List (low evidence)
Rare multisystem ciliopathy disorders v1.157 XPNPEP3 Sarah Leigh Gene: xpnpep3 has been classified as Red List (Low Evidence).
Rare multisystem ciliopathy disorders v1.156 XPNPEP3 Sarah Leigh Classified gene: XPNPEP3 as Amber List (moderate evidence)
Rare multisystem ciliopathy disorders v1.156 XPNPEP3 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review, however, reviewers on the Primary ciliary disorders (https://panelapp.genomicsengland.co.uk/panels/178/gene/XPNPEP3/#!review) question the relevance of the phenotype associated with variants in XPNPEP3. Helen Brittain (GEL Clinical Fellow) has been consulted regarding this issue.
Rare multisystem ciliopathy disorders v1.156 XPNPEP3 Sarah Leigh Gene: xpnpep3 has been classified as Amber List (Moderate Evidence).
Primary ciliary disorders v1.40 XPNPEP3 Sarah Leigh Classified gene: XPNPEP3 as Red List (low evidence)
Primary ciliary disorders v1.40 XPNPEP3 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review, however, the reviewers question the relevance of the phenotype associated with variants in XPNPEP3. Helen Brittain (GEL Clinical Fellow) has been consulted regarding this issue.
Primary ciliary disorders v1.40 XPNPEP3 Sarah Leigh Gene: xpnpep3 has been classified as Red List (Low Evidence).
Primary ciliary disorders v1.39 XPNPEP3 Sarah Leigh reviewed gene: XPNPEP3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Renal ciliopathies v1.49 XPNPEP3 Sarah Leigh edited their review of gene: XPNPEP3: Added comment: Associated with relevant phenotype in OMIM and as limited Gen2Phen gene. At least three variants were reported in three unrelated cases (PMID: 32660933; 20179356). Two of the variants were terminating (RCV000000069, RCV001554332) and the third was a missense variant (RCV000000068), that seems to activate a cryptic splice site; RT-PCR of lymphoblastoid cells showed that this resulted in the inclusion of intronic bases and a frameshift. Cilia-related function was examined by the suppression of zebrafish xpnpep3, resulting in phenotypes reminiscent of ciliopathy morphants, this effect was rescued by human XPNPEP3 that was devoid of a mitochondrial localization signal (PMID: 20179356).; Changed rating: GREEN
Mitochondrial disorders v2.84 XPNPEP3 Sarah Leigh changed review comment from: Associated with relevant phenotype in OMIM and as limited Gen2Phen gene. At least three variants reported in three unrelated cases (PMID: 32660933; 20179356). Two of the variants were terminating (RCV000000069, RCV001554332) and the third variant was a missense variant (RCV000000068), that seems to activate a cryptic splice site; RT-PCR of lymphoblastoid cells showed that this resulted in the inclusion of intronic bases and a frameshift. Cilia-related function was examined by the suppression of zebrafish xpnpep3, resulting in phenotypes reminiscent of ciliopathy morphants, this effect was rescued by human XPNPEP3 that was devoid of a mitochondrial localization signal (PMID: 20179356).; to: Associated with relevant phenotype in OMIM and as limited Gen2Phen gene. At least three variants were reported in three unrelated cases (PMID: 32660933; 20179356). Two of the variants were terminating (RCV000000069, RCV001554332) and the third was a missense variant (RCV000000068), that seems to activate a cryptic splice site; RT-PCR of lymphoblastoid cells showed that this resulted in the inclusion of intronic bases and a frameshift. Cilia-related function was examined by the suppression of zebrafish xpnpep3, resulting in phenotypes reminiscent of ciliopathy morphants, this effect was rescued by human XPNPEP3 that was devoid of a mitochondrial localization signal (PMID: 20179356).
Mitochondrial disorders v2.84 XPNPEP3 Sarah Leigh changed review comment from: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review, however, Zornitza Stark (Australian Genomics) has commented that the phenotype is not strickly a mitochondrial disorder.; to: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review, however, Zornitza Stark (Australian Genomics) has commented that the phenotype is not strictly a mitochondrial disorder.
Mitochondrial disorders v2.84 XPNPEP3 Sarah Leigh changed review comment from: Associated with relevant phenotype in OMIM and as limited Gen2Phen gene. At least three variants reported in three unrelated cases (PMID: 32660933; 20179356). Two of the variants were terminating (RCV000000069, RCV001554332) and the third variant was a missense variant (RCV000000068), that seems to activate a cryptic splice site; RT-PCR of lymphoblastoid cells showed that this resulted in the inclusion of intronic bases and a frameshift.; to: Associated with relevant phenotype in OMIM and as limited Gen2Phen gene. At least three variants reported in three unrelated cases (PMID: 32660933; 20179356). Two of the variants were terminating (RCV000000069, RCV001554332) and the third variant was a missense variant (RCV000000068), that seems to activate a cryptic splice site; RT-PCR of lymphoblastoid cells showed that this resulted in the inclusion of intronic bases and a frameshift. Cilia-related function was examined by the suppression of zebrafish xpnpep3, resulting in phenotypes reminiscent of ciliopathy morphants, this effect was rescued by human XPNPEP3 that was devoid of a mitochondrial localization signal (PMID: 20179356).
Mitochondrial disorders v2.84 XPNPEP3 Sarah Leigh edited their review of gene: XPNPEP3: Added comment: Associated with relevant phenotype in OMIM and as limited Gen2Phen gene. At least three variants reported in three unrelated cases (PMID: 32660933; 20179356). Two of the variants were terminating (RCV000000069, RCV001554332) and the third variant was a missense variant (RCV000000068), that seems to activate a cryptic splice site; RT-PCR of lymphoblastoid cells showed that this resulted in the inclusion of intronic bases and a frameshift.; Changed rating: AMBER
Unexplained young onset end-stage renal disease v1.27 XPNPEP3 Sarah Leigh Classified gene: XPNPEP3 as Amber List (moderate evidence)
Unexplained young onset end-stage renal disease v1.27 XPNPEP3 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Unexplained young onset end-stage renal disease v1.27 XPNPEP3 Sarah Leigh Gene: xpnpep3 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v2.218 XPNPEP3 Sarah Leigh Classified gene: XPNPEP3 as Amber List (moderate evidence)
Likely inborn error of metabolism v2.218 XPNPEP3 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Likely inborn error of metabolism v2.218 XPNPEP3 Sarah Leigh Gene: xpnpep3 has been classified as Amber List (Moderate Evidence).
Cystic kidney disease v2.31 XPNPEP3 Sarah Leigh Tag Q1_22_rating tag was added to gene: XPNPEP3.
Tag Q1_22_phenotype tag was added to gene: XPNPEP3.
Cystic kidney disease v2.31 XPNPEP3 Sarah Leigh Classified gene: XPNPEP3 as Amber List (moderate evidence)
Cystic kidney disease v2.31 XPNPEP3 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review, depending on review of the phenotype.
Cystic kidney disease v2.31 XPNPEP3 Sarah Leigh Gene: xpnpep3 has been classified as Amber List (Moderate Evidence).
Tubulointerstitial kidney disease v1.14 XPNPEP3 Sarah Leigh Classified gene: XPNPEP3 as Amber List (moderate evidence)
Tubulointerstitial kidney disease v1.14 XPNPEP3 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Tubulointerstitial kidney disease v1.14 XPNPEP3 Sarah Leigh Gene: xpnpep3 has been classified as Amber List (Moderate Evidence).
Unexplained kidney failure in young people v1.103 XPNPEP3 Sarah Leigh Classified gene: XPNPEP3 as Amber List (moderate evidence)
Unexplained kidney failure in young people v1.103 XPNPEP3 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Unexplained kidney failure in young people v1.103 XPNPEP3 Sarah Leigh Gene: xpnpep3 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.94 FOXL2 Ronnie Wright changed review comment from: Recent request from clinician to specifically interrogate this gene from WGS data because BPES was clinically suspected in a patient and they were surprised it was not included in the R27 'congenital malformation and dysmorphism syndromes' gene list (paediatric disorders panel).
Sources: Other, NHS GMS; to: Recent request from clinician to specifically interrogate this gene from WGS data because BPES was clinically suspected in a patient and they were surprised it was not included in the R27 'congenital malformation and dysmorphism syndromes' gene list (paediatric disorders panel).
Sources: Other, NHS GMS
Paediatric disorders - additional genes v1.94 FOXL2 Ronnie Wright changed review comment from: Recent request from clinician to specifically interrogate this gene from WGS data because it was clinically suspected in a patient and they were surprised it was not included in R27 congenital malformation and dysmorphism syndromes gene list (paediatric disorders panel).
Sources: Other, NHS GMS; to: Recent request from clinician to specifically interrogate this gene from WGS data because BPES was clinically suspected in a patient and they were surprised it was not included in the R27 'congenital malformation and dysmorphism syndromes' gene list (paediatric disorders panel).
Sources: Other, NHS GMS
DDG2P v2.60 XPNPEP3 Sarah Leigh Classified gene: XPNPEP3 as Amber List (moderate evidence)
DDG2P v2.60 XPNPEP3 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
DDG2P v2.60 XPNPEP3 Sarah Leigh Gene: xpnpep3 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.94 FOXL2 Ronnie Wright gene: FOXL2 was added
gene: FOXL2 was added to Paediatric disorders - additional genes. Sources: Other,NHS GMS
Mode of inheritance for gene: FOXL2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Penetrance for gene: FOXL2 were set to unknown
Review for gene: FOXL2 was set to AMBER
Added comment: Recent request from clinician to specifically interrogate this gene from WGS data because it was clinically suspected in a patient and they were surprised it was not included in R27 congenital malformation and dysmorphism syndromes gene list (paediatric disorders panel).
Sources: Other, NHS GMS
Malignant hyperthermia v0.1 STAC3 Arina Puzriakova gene: STAC3 was added
gene: STAC3 was added to Malignant hyperthermia. Sources: Expert Review Green
Mode of inheritance for gene: STAC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STAC3 were set to 31559918; 18553514; 30168660
Phenotypes for gene: STAC3 were set to Myopathy, congenital, with myopathic facies, scoliosis, and malignant hyperthermia; Myopathy, congenital, Baily-Bloch, OMIM:255995
Malignant hyperthermia v0.1 CACNA1S Arina Puzriakova gene: CACNA1S was added
gene: CACNA1S was added to Malignant hyperthermia. Sources: Expert Review Green
Mode of inheritance for gene: CACNA1S was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CACNA1S were set to 31559918; 9199552; 11260227
Phenotypes for gene: CACNA1S were set to {Malignant hyperthermia susceptibility 5}, OMIM:601887
Malignant hyperthermia v0.1 RYR1 Arina Puzriakova gene: RYR1 was added
gene: RYR1 was added to Malignant hyperthermia. Sources: Expert Review Green
Mode of inheritance for gene: RYR1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RYR1 were set to 31559918; 16163667; 32919876; 31737266; 33767344; 34462577
Phenotypes for gene: RYR1 were set to {Malignant hyperthermia susceptibility 1}, OMIM:145600
Mitochondrial disorders v2.84 XPNPEP3 Sarah Leigh Classified gene: XPNPEP3 as Amber List (moderate evidence)
Mitochondrial disorders v2.84 XPNPEP3 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review, however, Zornitza Stark (Australian Genomics) has commented that the phenotype is not strickly a mitochondrial disorder.
Mitochondrial disorders v2.84 XPNPEP3 Sarah Leigh Gene: xpnpep3 has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v2.84 XPNPEP3 Sarah Leigh Classified gene: XPNPEP3 as Amber List (moderate evidence)
Mitochondrial disorders v2.84 XPNPEP3 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review, however, Zornitza Stark (Australian Genomics) has commented that the phenotype is not strickly a mitochondrial disorder.
Mitochondrial disorders v2.84 XPNPEP3 Sarah Leigh Gene: xpnpep3 has been classified as Amber List (Moderate Evidence).
Renal ciliopathies v1.49 XPNPEP3 Sarah Leigh Tag Q1_22_rating tag was added to gene: XPNPEP3.
Renal ciliopathies v1.49 XPNPEP3 Sarah Leigh Classified gene: XPNPEP3 as Amber List (moderate evidence)
Renal ciliopathies v1.49 XPNPEP3 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Renal ciliopathies v1.49 XPNPEP3 Sarah Leigh Gene: xpnpep3 has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v2.83 XPNPEP3 Sarah Leigh Tag Q2_21_phenotype tag was added to gene: XPNPEP3.
Tag Q1_22_rating tag was added to gene: XPNPEP3.
Unexplained young onset end-stage renal disease v1.26 XPNPEP3 Sarah Leigh Mode of inheritance for gene: XPNPEP3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cystic kidney disease v2.30 XPNPEP3 Sarah Leigh Mode of inheritance for gene: XPNPEP3 was changed from to BIALLELIC, autosomal or pseudoautosomal
Unexplained kidney failure in young people v1.102 XPNPEP3 Sarah Leigh Mode of inheritance for gene: XPNPEP3 was changed from to BIALLELIC, autosomal or pseudoautosomal
Primary ciliary disorders v1.39 XPNPEP3 Sarah Leigh Mode of inheritance for gene: XPNPEP3 was changed from to BIALLELIC, autosomal or pseudoautosomal
Cystic kidney disease v2.29 XPNPEP3 Sarah Leigh Publications for gene: XPNPEP3 were set to
Intellectual disability v3.1493 XPNPEP3 Sarah Leigh Publications for gene: XPNPEP3 were set to 20179356
Tubulointerstitial kidney disease v1.13 XPNPEP3 Sarah Leigh Publications for gene: XPNPEP3 were set to 20179356
Unexplained kidney failure in young people v1.101 XPNPEP3 Sarah Leigh Publications for gene: XPNPEP3 were set to
Rare multisystem ciliopathy disorders v1.155 XPNPEP3 Sarah Leigh Publications for gene: XPNPEP3 were set to 20179356
DDG2P v2.59 XPNPEP3 Sarah Leigh Publications for gene: XPNPEP3 were set to 20179356
Renal ciliopathies v1.48 XPNPEP3 Sarah Leigh Publications for gene: XPNPEP3 were set to 20179356
Primary ciliary disorders v1.38 XPNPEP3 Sarah Leigh Publications for gene: XPNPEP3 were set to
Mitochondrial disorders v2.83 XPNPEP3 Sarah Leigh Phenotypes for gene: XPNPEP3 were changed from nephronophthisis-like nephropathy to Nephronophthisis-like nephropathy 1 OMIM:613159; nephronophthisis-like nephropathy 1 MONDO:0013163
Likely inborn error of metabolism v2.217 XPNPEP3 Sarah Leigh Phenotypes for gene: XPNPEP3 were changed from nephronophthisis-like nephropathy to Nephronophthisis-like nephropathy 1 OMIM:613159; nephronophthisis-like nephropathy 1 MONDO:0013163
Unexplained young onset end-stage renal disease v1.25 XPNPEP3 Sarah Leigh Phenotypes for gene: XPNPEP3 were changed from Ciliopathy genes associated with cystic kidney disease to Nephronophthisis-like nephropathy 1 OMIM:613159; nephronophthisis-like nephropathy 1 MONDO:0013163
Cystic kidney disease v2.28 XPNPEP3 Sarah Leigh Phenotypes for gene: XPNPEP3 were changed from Ciliopathy genes associated with cystic kidney disease to Nephronophthisis-like nephropathy 1 OMIM:613159; nephronophthisis-like nephropathy 1 MONDO:0013163
Tubulointerstitial kidney disease v1.12 XPNPEP3 Sarah Leigh Phenotypes for gene: XPNPEP3 were changed from Nephronopthisis-like nephropathy 1 MIM 613159 to Nephronophthisis-like nephropathy 1 OMIM:613159; nephronophthisis-like nephropathy 1 MONDO:0013163
Unexplained kidney failure in young people v1.100 XPNPEP3 Sarah Leigh Phenotypes for gene: XPNPEP3 were changed from Ciliopathy genes associated with cystic kidney disease to Nephronophthisis-like nephropathy 1 OMIM:613159; nephronophthisis-like nephropathy 1 MONDO:0013163
Intellectual disability v3.1492 XPNPEP3 Sarah Leigh Phenotypes for gene: XPNPEP3 were changed from Nephronophthisis-like nephropathy 1, 613159 to Nephronophthisis-like nephropathy 1 OMIM:613159; nephronophthisis-like nephropathy 1 MONDO:0013163
Rare multisystem ciliopathy disorders v1.154 XPNPEP3 Sarah Leigh Phenotypes for gene: XPNPEP3 were changed from Nephronophthisis-like nephropathy 1, 613159; Ciliopathies; Nephronophthisis to Nephronophthisis-like nephropathy 1 OMIM:613159; nephronophthisis-like nephropathy 1 MONDO:0013163
DDG2P v2.58 XPNPEP3 Sarah Leigh Phenotypes for gene: XPNPEP3 were changed from NEPHRONOPHTHISIS-LIKE NEPHROPATHY TYPE 1 613159 to Nephronophthisis-like nephropathy 1 OMIM:613159; nephronophthisis-like nephropathy 1 MONDO:0013163
Primary ciliary disorders v1.37 XPNPEP3 Sarah Leigh Phenotypes for gene: XPNPEP3 were changed from ciliopathies to Nephronophthisis-like nephropathy 1 OMIM:613159; nephronophthisis-like nephropathy 1 MONDO:0013163
Renal ciliopathies v1.47 XPNPEP3 Sarah Leigh Phenotypes for gene: XPNPEP3 were changed from Nephronophthisis; Ciliopathies; Nephronophthisis-like nephropathy 1, 613159 to Nephronophthisis-like nephropathy 1 OMIM:613159; nephronophthisis-like nephropathy 1 MONDO:0013163
Malignant hyperthermia v0.0 Arina Puzriakova Added Panel Malignant hyperthermia
Set list of related panels to R371
Set panel types to: GMS Rare Disease
Likely inborn error of metabolism v2.216 XPNPEP3 Sarah Leigh Publications for gene: XPNPEP3 were set to PMID: 20179356
Unexplained young onset end-stage renal disease v1.24 XPNPEP3 Sarah Leigh Publications for gene: XPNPEP3 were set to
Mitochondrial disorders v2.82 XPNPEP3 Sarah Leigh Publications for gene: XPNPEP3 were set to 20179356
Mitochondrial disorders v2.81 XPNPEP3 Sarah Leigh Publications for gene: XPNPEP3 were set to PMID: 20179356
Autoinflammatory disorders v0.8 UBA1 Arina Puzriakova Publications for gene: UBA1 were set to 34048852; 33108101
Autoinflammatory disorders v0.7 UBA1 Arina Puzriakova reviewed gene: UBA1: Rating: ; Mode of pathogenicity: None; Publications: 33108101, 33690815, 34048852, 34077651, 34196684; Phenotypes: VEXAS syndrome, somatic, OMIM:301054; Mode of inheritance: None
Autoinflammatory disorders v0.7 UBA1 Arina Puzriakova Tag somatic tag was added to gene: UBA1.
Autoinflammatory disorders v0.7 SH3BP2 Arina Puzriakova Publications for gene: SH3BP2 were set to 25705883; 25220465; 26152156; 25470448
Autoinflammatory disorders v0.6 SH3BP2 Arina Puzriakova reviewed gene: SH3BP2: Rating: ; Mode of pathogenicity: None; Publications: 26152156, 25705883, 25470448, 25220465, 32825821; Phenotypes: Cherubism, OMIM:118400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
COVID-19 research v1.114 PSMB9 Arina Puzriakova Publications for gene: PSMB9 were set to 26524591
Primary immunodeficiency or monogenic inflammatory bowel disease v2.526 PSMB9 Arina Puzriakova Added comment: Comment on mode of inheritance: Updated MOI from biallelic to monoallelic as all cases reported to date have harboured heterozygous variants in this gene (PMID: 26524591; 33727065; 34819510)
Primary immunodeficiency or monogenic inflammatory bowel disease v2.526 PSMB9 Arina Puzriakova Mode of inheritance for gene: PSMB9 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
COVID-19 research v1.113 PSMB9 Arina Puzriakova Added comment: Comment on mode of inheritance: Updated MOI from biallelic to monoallelic as all cases reported to date have harboured heterozygous variants in this gene (PMID: 26524591; 33727065; 34819510)
COVID-19 research v1.113 PSMB9 Arina Puzriakova Mode of inheritance for gene: PSMB9 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Autoinflammatory disorders v0.6 PSMB9 Arina Puzriakova Added comment: Comment on mode of inheritance: Updated MOI from biallelic to monoallelic as all cases reported to date have harboured heterozygous variants in this gene (PMID: 26524591; 33727065; 34819510)
Autoinflammatory disorders v0.6 PSMB9 Arina Puzriakova Mode of inheritance for gene: PSMB9 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Autoinflammatory disorders v0.5 PSMB9 Arina Puzriakova Publications for gene: PSMB9 were set to 26524591; 33727065
Primary immunodeficiency or monogenic inflammatory bowel disease v2.525 PSMB9 Arina Puzriakova Publications for gene: PSMB9 were set to 26524591; 33727065
Primary immunodeficiency or monogenic inflammatory bowel disease v2.524 PSMB9 Arina Puzriakova edited their review of gene: PSMB9: Added comment: Kanazawa et al., 2021 (PMID: 34819510) identified a further two unrelated Japanese patients with the same de novo PSMB9 heterozygous missense variant as that identified in the previous study (c.467G>A/p.G156D). Both individuals displayed severe autoinflammatory phenotypes and pulmonary hypertension and later also manifested combined immunodeficiency with periodic inflammatory exacerbation. The variant lead to impaired immunoproteasome maturation and activity, and the proteasome defect and immunodeficient phenotypes were recapitulated in Psmb9(G156D/+) mice.; Changed publications to: 33727065, 34819510; Changed phenotypes to: Proteasome-associated autoinflammatory syndrome 3, digenic, OMIM:617591
Autoinflammatory disorders v0.4 PSMB9 Arina Puzriakova reviewed gene: PSMB9: Rating: ; Mode of pathogenicity: None; Publications: 26524591, 33727065, 34819510; Phenotypes: Proteasome-associated autoinflammatory syndrome 3, digenic, OMIM:617591; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Cystic kidney disease v2.27 IFT140 Daniel Gale gene: IFT140 was added
gene: IFT140 was added to Cystic kidney disease. Sources: Literature,Research
Mode of inheritance for gene: IFT140 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IFT140 were set to 34890546
Phenotypes for gene: IFT140 were set to Cystic kidney disease; chronic kidney disease
Penetrance for gene: IFT140 were set to unknown
Review for gene: IFT140 was set to GREEN
Added comment: Very strong evidence of association of truncating IFT140 mutations and cystic kidney disease in cited paper, which includes 12 multiplex families and 26 singletons. In addition, hypothesis-free region-based variance testing (SKAT-O) independently identifying truncating variants in this gene in 100,000 Genomes Project (p=3.5e-17) and UK BioBank (p=4.5e-15) participants with cystic kidney disease (see https://genebass.org/gene/undefined/phenotype/icd_first_occurrence-132532-both_sexes--?resultIndex=gene-manhattan&resultLayout=full for UKBB analysis).
Sources: Literature, Research
Autoinflammatory disorders v0.4 PSMB4 Arina Puzriakova reviewed gene: PSMB4: Rating: ; Mode of pathogenicity: None; Publications: 34416217, 26524591; Phenotypes: Proteasome-associated autoinflammatory syndrome 3 and digenic forms, OMIM:617591; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rare syndromic craniosynostosis or isolated multisuture synostosis v2.61 HNRNPK Eleanor Williams commented on gene: HNRNPK: Review and publication noted by Helen Lord adds further weight to rating this gene green.
Rare syndromic craniosynostosis or isolated multisuture synostosis v2.61 HNRNPK Eleanor Williams Added comment: Comment on publications: Added further paper PMID:32588992 - Yamada et al 2020
Rare syndromic craniosynostosis or isolated multisuture synostosis v2.61 HNRNPK Eleanor Williams Publications for gene: HNRNPK were set to 26173930; 26954065; 28771707; 29904177; 24501764; 25348648; 28374925
Monogenic hearing loss v2.218 SPATA5L1 Ivone Leong Phenotypes for gene: SPATA5L1 were changed from Neurodevelopmental disorder with hearing loss and spasticity, OMIM:619616 to Neurodevelopmental disorder with hearing loss and spasticity, OMIM:619616; Deafness, autosomal recessive 119, OMIM:619615
Monogenic hearing loss v2.217 SPATA5L1 Ivone Leong Entity copied from Intellectual disability v3.1491
Monogenic hearing loss v2.217 SPATA5L1 Ivone Leong gene: SPATA5L1 was added
gene: SPATA5L1 was added to Hearing loss. Sources: Expert Review Amber,Literature
Q1_22_rating tags were added to gene: SPATA5L1.
Mode of inheritance for gene: SPATA5L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPATA5L1 were set to 34626583
Phenotypes for gene: SPATA5L1 were set to Neurodevelopmental disorder with hearing loss and spasticity, OMIM:619616
Severe microcephaly v2.277 SPATA5L1 Ivone Leong Entity copied from Intellectual disability v3.1491
Severe microcephaly v2.277 SPATA5L1 Ivone Leong gene: SPATA5L1 was added
gene: SPATA5L1 was added to Severe microcephaly. Sources: Expert Review Amber,Literature
Q1_22_rating tags were added to gene: SPATA5L1.
Mode of inheritance for gene: SPATA5L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPATA5L1 were set to 34626583
Phenotypes for gene: SPATA5L1 were set to Neurodevelopmental disorder with hearing loss and spasticity, OMIM:619616
Early onset or syndromic epilepsy v2.486 SPATA5L1 Ivone Leong Entity copied from Intellectual disability v3.1491
Early onset or syndromic epilepsy v2.486 SPATA5L1 Ivone Leong gene: SPATA5L1 was added
gene: SPATA5L1 was added to Genetic epilepsy syndromes. Sources: Expert Review Amber,Literature
Q1_22_rating tags were added to gene: SPATA5L1.
Mode of inheritance for gene: SPATA5L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPATA5L1 were set to 34626583
Phenotypes for gene: SPATA5L1 were set to Neurodevelopmental disorder with hearing loss and spasticity, OMIM:619616
Intellectual disability v3.1491 SPATA5L1 Ivone Leong Classified gene: SPATA5L1 as Amber List (moderate evidence)
Intellectual disability v3.1491 SPATA5L1 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in OMIM and Gene2Phenotype (limited). There is enough evidence to support a gene-disease association, this gene should be rated Green.
Intellectual disability v3.1491 SPATA5L1 Ivone Leong Gene: spata5l1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v3.1490 SPATA5L1 Ivone Leong Tag Q1_22_rating tag was added to gene: SPATA5L1.
Intellectual disability v3.1490 SPATA5L1 Ivone Leong Phenotypes for gene: SPATA5L1 were changed from Neurodevelopmental disorder with hearing loss and spasticity, MIM# 619616 to Neurodevelopmental disorder with hearing loss and spasticity, OMIM:619616
Renal ciliopathies v1.46 PDIA6 Eleanor Williams commented on gene: PDIA6: Added this gene to this panel on advice from Genomics England clinical team. Rating amber as 1 case plus functional data.
Skeletal dysplasia v2.168 PDIA6 Eleanor Williams commented on gene: PDIA6: Added this gene to this panel on advice from Genomics England clinical team. Rating amber as 1 case plus functional data.
Neonatal diabetes v2.35 PDIA6 Eleanor Williams commented on gene: PDIA6: Added this gene to this panel on advice from Genomics England clinical team. Rating amber as 1 case plus functional data.
Renal ciliopathies v1.46 PDIA6 Eleanor Williams Entity copied from Skeletal ciliopathies v1.15
Renal ciliopathies v1.46 PDIA6 Eleanor Williams gene: PDIA6 was added
gene: PDIA6 was added to Renal ciliopathies. Sources: Literature,Expert Review Amber
Mode of inheritance for gene: PDIA6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDIA6 were set to 33495992
Phenotypes for gene: PDIA6 were set to Asphyxiating thoracic dystrophy (ATD) syndrome and infantile‐onset diabetes
Autoinflammatory disorders v0.4 PSMB4 Arina Puzriakova Tag digenic tag was added to gene: PSMB4.
Neonatal diabetes v2.35 PDIA6 Eleanor Williams Entity copied from Skeletal ciliopathies v1.15
Neonatal diabetes v2.35 PDIA6 Eleanor Williams gene: PDIA6 was added
gene: PDIA6 was added to Diabetes - neonatal onset. Sources: Literature,Expert Review Amber
Mode of inheritance for gene: PDIA6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDIA6 were set to 33495992
Phenotypes for gene: PDIA6 were set to Asphyxiating thoracic dystrophy (ATD) syndrome and infantile‐onset diabetes
Skeletal dysplasia v2.168 PDIA6 Eleanor Williams Entity copied from Skeletal ciliopathies v1.15
Skeletal dysplasia v2.168 PDIA6 Eleanor Williams gene: PDIA6 was added
gene: PDIA6 was added to Skeletal dysplasia. Sources: Literature,Expert Review Amber
Mode of inheritance for gene: PDIA6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDIA6 were set to 33495992
Phenotypes for gene: PDIA6 were set to Asphyxiating thoracic dystrophy (ATD) syndrome and infantile‐onset diabetes
Autoinflammatory disorders v0.4 TMEM173 Arina Puzriakova Tag new-gene-name tag was added to gene: TMEM173.
Early onset or syndromic epilepsy v2.485 SCN8A Sarah Leigh changed review comment from: Comment on mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown from BOTH monoallelic and biallelic, autosomal or pseudoautosomal, while the strength of the evidence is reviewed.; to: Comment on mode of inheritance: The mode of inheritance has been reverted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown from BOTH monoallelic and biallelic, autosomal or pseudoautosomal, while the strength of the evidence is reviewed.
Autoinflammatory disorders v0.4 Arina Puzriakova List of related panels changed from to R413
Early onset or syndromic epilepsy v2.485 SCN8A Sarah Leigh Added comment: Comment on mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown from BOTH monoallelic and biallelic, autosomal or pseudoautosomal, while the strength of the evidence is reviewed.
Early onset or syndromic epilepsy v2.485 SCN8A Sarah Leigh Mode of inheritance for gene: SCN8A was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Autoinflammatory disorders v0.3 ADA2 Arina Puzriakova gene: ADA2 was added
gene: ADA2 was added to Autoinflammatory disorders. Sources: Expert Review Green
Mode of inheritance for gene: ADA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADA2 were set to 24552285; 29564582; 27059682; 24552284; 26922074; 27444081
Phenotypes for gene: ADA2 were set to Vasculitis, autoinflammation, immunodeficiency, and hematologic defects syndrome, OMIM:615688
Autoinflammatory disorders v0.3 CARD14 Arina Puzriakova gene: CARD14 was added
gene: CARD14 was added to Autoinflammatory disorders. Sources: Expert Review Green
Mode of inheritance for gene: CARD14 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CARD14 were set to 29980436; 22521418; 22703878; 29704870; 23648549; 23067081; 29689250; 23711932; 30248356
Phenotypes for gene: CARD14 were set to Psoriasis 2, OMIM:602723; Pityriasis rubra pilaris, OMIM:173200
Autoinflammatory disorders v0.3 UBA1 Arina Puzriakova gene: UBA1 was added
gene: UBA1 was added to Autoinflammatory disorders. Sources: Expert Review Red
Mode of inheritance for gene: UBA1 was set to Other
Publications for gene: UBA1 were set to 34048852; 33108101
Phenotypes for gene: UBA1 were set to VEXAS syndrome, somatic, OMIM:301054
Autoinflammatory disorders v0.3 TNFAIP3 Arina Puzriakova gene: TNFAIP3 was added
gene: TNFAIP3 was added to Autoinflammatory disorders. Sources: Expert Review Green
Mode of inheritance for gene: TNFAIP3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TNFAIP3 were set to 29317407; 29572183; 27845235; 28659290; 31164164; 26642243
Phenotypes for gene: TNFAIP3 were set to Autoinflammatory syndrome, familial, Behcet-like, OMIM:616744
Autoinflammatory disorders v0.3 TMEM173 Arina Puzriakova gene: TMEM173 was added
gene: TMEM173 was added to Autoinflammatory disorders. Sources: Expert Review Green
Mode of inheritance for gene: TMEM173 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TMEM173 were set to 25401470; 29491158; 29425920; 30705050; 25029335; 29976662
Phenotypes for gene: TMEM173 were set to STING-associated vasculopathy, infantile-onset, OMIM:615934
Autoinflammatory disorders v0.3 TNFRSF1A Arina Puzriakova gene: TNFRSF1A was added
gene: TNFRSF1A was added to Autoinflammatory disorders. Sources: Expert Review Green
Mode of inheritance for gene: TNFRSF1A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TNFRSF1A were set to 10199409; 10902757; 23965844; 12209523; 17360963; 11175303; 11115159
Phenotypes for gene: TNFRSF1A were set to Periodic fever, familial, OMIM:142680
Autoinflammatory disorders v0.3 SLC29A3 Arina Puzriakova gene: SLC29A3 was added
gene: SLC29A3 was added to Autoinflammatory disorders. Sources: Expert Review Green
Mode of inheritance for gene: SLC29A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC29A3 were set to 22238637; 18940313; 20619369; 20140240; 19336477; 16650224; 23530176; 22653152; 16118898; 22875837; 21888995; 19175903; 21178579
Phenotypes for gene: SLC29A3 were set to Histiocytosis-lymphadenopathy plus syndrome, OMIM:602782
Autoinflammatory disorders v0.3 SH3BP2 Arina Puzriakova gene: SH3BP2 was added
gene: SH3BP2 was added to Autoinflammatory disorders. Sources: Expert Review Red
Mode of inheritance for gene: SH3BP2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SH3BP2 were set to 25705883; 25220465; 26152156; 25470448
Phenotypes for gene: SH3BP2 were set to Cherubism, OMIM:118400
Autoinflammatory disorders v0.3 RBCK1 Arina Puzriakova gene: RBCK1 was added
gene: RBCK1 was added to Autoinflammatory disorders. Sources: Expert Review Green
Mode of inheritance for gene: RBCK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RBCK1 were set to 23798481; 610924; 23104095; 29260357
Phenotypes for gene: RBCK1 were set to Polyglucosan body myopathy 1 with or without immunodeficiency, OMIM:615895
Autoinflammatory disorders v0.3 PSTPIP1 Arina Puzriakova gene: PSTPIP1 was added
gene: PSTPIP1 was added to Autoinflammatory disorders. Sources: Expert Review Green
Mode of inheritance for gene: PSTPIP1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PSTPIP1 were set to 29575118; 28960754; 28251506; 26025129; 9212761; 21532836; 28628471; 22161697
Phenotypes for gene: PSTPIP1 were set to Pyogenic sterile arthritis, pyoderma gangrenosum, and acne, OMIM:604416
Autoinflammatory disorders v0.3 PSMB9 Arina Puzriakova gene: PSMB9 was added
gene: PSMB9 was added to Autoinflammatory disorders. Sources: Expert Review Amber
Mode of inheritance for gene: PSMB9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMB9 were set to 26524591; 33727065
Phenotypes for gene: PSMB9 were set to CANDLE syndrome (Autoinflammation, lipodystrophy, and dermatosis syndrome); Proteasome-associated autoinflammatory syndrome 3, digenic, OMIM:617591
Autoinflammatory disorders v0.3 PSMB8 Arina Puzriakova gene: PSMB8 was added
gene: PSMB8 was added to Autoinflammatory disorders. Sources: Expert Review Green
Mode of inheritance for gene: PSMB8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMB8 were set to 21852578; 21953331; 20534754; 20159315; 21881205; 21129723
Phenotypes for gene: PSMB8 were set to Proteasome-associated autoinflammatory syndrome 1 and digenic forms, OMIM:256040
Autoinflammatory disorders v0.3 PSMB4 Arina Puzriakova gene: PSMB4 was added
gene: PSMB4 was added to Autoinflammatory disorders. Sources: Expert Review Amber
Mode of inheritance for gene: PSMB4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMB4 were set to 34416217; 26524591
Phenotypes for gene: PSMB4 were set to CANDLE syndrome (Autoinflammation, lipodystrophy, and dermatosis syndrome); Proteasome-associated autoinflammatory syndrome 3 and digenic forms, OMIM:617591
Autoinflammatory disorders v0.3 PLCG2 Arina Puzriakova gene: PLCG2 was added
gene: PLCG2 was added to Autoinflammatory disorders. Sources: Expert Review Green
Mode of inheritance for gene: PLCG2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PLCG2 were set to 29538758; 22236196; 23000145; 25760457
Phenotypes for gene: PLCG2 were set to Autoinflammation, antibody deficiency, and immune dysregulation syndrome, OMIM:614878; Familial cold autoinflammatory syndrome 3, OMIM:614468
Autoinflammatory disorders v0.3 OTULIN Arina Puzriakova gene: OTULIN was added
gene: OTULIN was added to Autoinflammatory disorders. Sources: Expert Review Green
Mode of inheritance for gene: OTULIN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OTULIN were set to 27559085; 27523608
Phenotypes for gene: OTULIN were set to Autoinflammation, panniculitis, and dermatosis syndrome, OMIM:617099
Autoinflammatory disorders v0.3 NOD2 Arina Puzriakova gene: NOD2 was added
gene: NOD2 was added to Autoinflammatory disorders. Sources: Expert Review Green
Mode of inheritance for gene: NOD2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NOD2 were set to 11385576; 25136265; 19479837; 25416713; 21914217; 26070941
Phenotypes for gene: NOD2 were set to {Inflammatory bowel disease 1, Crohn disease}, OMIM:266600; Blau syndrome, OMIM:186580; {Yao syndrome}, OMIM:617321
Autoinflammatory disorders v0.3 NLRP3 Arina Puzriakova gene: NLRP3 was added
gene: NLRP3 was added to Autoinflammatory disorders. Sources: Expert Review Green
Mode of inheritance for gene: NLRP3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NLRP3 were set to 11687797; 18423104; 11992256; 14872505; 29366613; 11590390; 12032915; 12522564; 28847925
Phenotypes for gene: NLRP3 were set to Deafness, autosomal dominant 34, with or without inflammation, OMIM:617772; Familial cold inflammatory syndrome 1, OMIM:120100; Muckle-Wells syndrome, OMIM:191900; CINCA syndrome, OMIM:607115
Autoinflammatory disorders v0.3 NLRP12 Arina Puzriakova gene: NLRP12 was added
gene: NLRP12 was added to Autoinflammatory disorders. Sources: Expert Review Green
Mode of inheritance for gene: NLRP12 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NLRP12 were set to 21360512; 27779193; 27633793; 29178652; 18230725; 29248470
Phenotypes for gene: NLRP12 were set to Familial cold autoinflammatory syndrome 2, OMIM:611762
Autoinflammatory disorders v0.3 NLRC4 Arina Puzriakova gene: NLRC4 was added
gene: NLRC4 was added to Autoinflammatory disorders. Sources: Expert Review Green
Mode of inheritance for gene: NLRC4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NLRC4 were set to 27876626; 25217959; 25385754; 25217960
Phenotypes for gene: NLRC4 were set to Autoinflammation with infantile enterocolitis, OMIM:616050; ?Familial cold autoinflammatory syndrome 4, OMIM:616115
Autoinflammatory disorders v0.3 MVK Arina Puzriakova gene: MVK was added
gene: MVK was added to Autoinflammatory disorders. Sources: Expert Review Green
Mode of inheritance for gene: MVK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MVK were set to 21708801; 16435210; 22038276; 10369261; 19011501
Phenotypes for gene: MVK were set to Mevalonic aciduria, OMIM:610377; Hyper-IgD syndrome, OMIM:260920
Autoinflammatory disorders v0.3 MEFV Arina Puzriakova gene: MEFV was added
gene: MEFV was added to Autoinflammatory disorders. Sources: Expert Review Green
Mode of inheritance for gene: MEFV was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: MEFV were set to 27030597; 9288094; 28835462; 14679589; 9288758; 10787449
Phenotypes for gene: MEFV were set to Familial Mediterranean fever, AR, OMIM:249100; Neutrophilic dermatosis, acute febrile, OMIM:608068; Familial Mediterranean fever, AD, OMIM:134610
Autoinflammatory disorders v0.3 LPIN2 Arina Puzriakova gene: LPIN2 was added
gene: LPIN2 was added to Autoinflammatory disorders. Sources: Expert Review Green
Mode of inheritance for gene: LPIN2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LPIN2 were set to 17330256; 27860302; 15994876; 29387759
Phenotypes for gene: LPIN2 were set to Majeed syndrome, OMIM:609628
Autoinflammatory disorders v0.3 IL36RN Arina Puzriakova gene: IL36RN was added
gene: IL36RN was added to Autoinflammatory disorders. Sources: Expert Review Green
Mode of inheritance for gene: IL36RN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IL36RN were set to 23698098; 21839423; 21848462; 23303454; 22903787
Phenotypes for gene: IL36RN were set to Psoriasis 14, pustular, OMIM:614204
Autoinflammatory disorders v0.3 IL1RN Arina Puzriakova gene: IL1RN was added
gene: IL1RN was added to Autoinflammatory disorders. Sources: Expert Review Green
Mode of inheritance for gene: IL1RN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IL1RN were set to 22127713; 19494219; 19494218
Phenotypes for gene: IL1RN were set to Interleukin 1 receptor antagonist deficiency, OMIM:612852
Cytopenia - NOT Fanconi anaemia v1.52 ADA2 Arina Puzriakova Phenotypes for gene: ADA2 were changed from Diamond Blackfan anaemia; 615688 Polyarteritis nodosa/Sneddon sydrome to Vasculitis, autoinflammation, immunodeficiency, and hematologic defects syndrome, OMIM:615688; Sneddon syndrome, OMIM:182410; Diamond-Blackfan Anemia
Rare anaemia v1.33 ADA2 Arina Puzriakova Phenotypes for gene: ADA2 were changed from Diamond Blackfan anaemia to Vasculitis, autoinflammation, immunodeficiency, and hematologic defects syndrome, OMIM:615688; Sneddon syndrome, OMIM:182410; Diamond-Blackfan Anemia
Cytopenias and congenital anaemias v1.96 ADA2 Arina Puzriakova Phenotypes for gene: ADA2 were changed from Vasculitis, autoinflammation, immunodeficiency, and hematologic defects syndrome, OMIM:615688; Diamond-Blackfan Anemia to Vasculitis, autoinflammation, immunodeficiency, and hematologic defects syndrome, OMIM:615688; Sneddon syndrome, OMIM:182410; Diamond-Blackfan Anemia
Cytopenias and congenital anaemias v1.95 ADA2 Arina Puzriakova Phenotypes for gene: ADA2 were changed from DBA; Diamond-Blackfan Anemia to Vasculitis, autoinflammation, immunodeficiency, and hematologic defects syndrome, OMIM:615688; Diamond-Blackfan Anemia
Early onset or syndromic epilepsy v2.484 SCN8A Sarah Leigh Deleted their comment
COVID-19 research v1.112 ADA2 Arina Puzriakova Phenotypes for gene: ADA2 were changed from Other autoinflammatory diseases with known genetic defect; Evans' syndrome; Polyarteritis nodosa, childhood-onset, 615688; combined immunodeficiency; Polyarteritis nodosa; Deficiency of ADA2 (DADA2); Polyarteritis nodosa, childhood-onset, early-onset recurrent ischemic stroke and fever; Autoinflammatory Disorders; Fever with early onset stroke; ADA2 deficiency to Vasculitis, autoinflammation, immunodeficiency, and hematologic defects syndrome, OMIM:615688; Polyarteritis nodosa, childhood-onset, early-onset recurrent ischemic stroke and fever; Autoinflammatory Disorders
Primary immunodeficiency or monogenic inflammatory bowel disease v2.524 ADA2 Arina Puzriakova Phenotypes for gene: ADA2 were changed from Polyarteritis nodosa; Polyarteritis nodosa, childhood-onset, 615688; ADA2 deficiency; Deficiency of ADA2 (DADA2); Other autoinflammatory diseases with known genetic defect; Fever with early onset stroke; combined immunodeficiency; Evans' syndrome; Polyarteritis nodosa, childhood-onset, early-onset recurrent ischemic stroke and fever; Autoinflammatory Disorders to Vasculitis, autoinflammation, immunodeficiency, and hematologic defects syndrome, OMIM:615688; Polyarteritis nodosa, childhood-onset, early-onset recurrent ischemic stroke and fever; Autoinflammatory Disorders
COVID-19 research v1.111 CARD14 Arina Puzriakova Phenotypes for gene: CARD14 were changed from Other autoinflammatory diseases with known genetic defect; Psoriasis 2, 602723; Autoinflammatory Disorders; Pityriasis rubra pilaris,173200; immune dysregulation; CARD14 mediated psoriasis; Psoriasis to Pityriasis rubra pilaris, OMIM:173200; Psoriasis 2, OMIM:602723; Autoinflammatory Disorders
Primary immunodeficiency or monogenic inflammatory bowel disease v2.523 CARD14 Arina Puzriakova Phenotypes for gene: CARD14 were changed from CARD14 mediated psoriasis; Psoriasis 2, 602723; Pityriasis rubra pilaris,173200; Other autoinflammatory diseases with known genetic defect; Psoriasis; Autoinflammatory Disorders; immune dysregulation to Pityriasis rubra pilaris, OMIM:173200; Psoriasis 2, OMIM:602723; Autoinflammatory Disorders
Palmoplantar keratoderma and erythrokeratodermas v1.23 CARD14 Arina Puzriakova Phenotypes for gene: CARD14 were changed from Pityriasis rubra pilaris, 173200; familial pityriasis rubra pilaris; keratotic follicular papules, well-demarcated salmon-colored erythematous plaques covered with fine powdery scales interspersed with distinct islands of uninvolved skin, and palmoplantar keratoderma to Pityriasis rubra pilaris, OMIM:173200; Psoriasis 2, OMIM:602723; Keratotic follicular papules, well-demarcated salmon-colored erythematous plaques covered with fine powdery scales interspersed with distinct islands of uninvolved skin, and palmoplantar keratoderma
Generalised pustular psoriasis v1.12 CARD14 Arina Puzriakova Phenotypes for gene: CARD14 were changed from CARD14 mediated psoriasis Psoriasis 2, 602723; Pityriasis rubra pilaris,173200; Other autoinflammatory diseases with known genetic defect to Psoriasis 2, OMIM:602723; Pityriasis rubra pilaris, OMIM:173200
Pityriasis rubra pilaris v1.2 CARD14 Arina Puzriakova Phenotypes for gene: CARD14 were changed from Pityriasis rubra pilaris; 173200 to Pityriasis rubra pilaris, OMIM:173200
Epidermolysis bullosa and congenital skin fragility v1.50 CARD14 Arina Puzriakova Phenotypes for gene: CARD14 were changed from Pityriasis rubra pilaris, 173200; PRP; thick scales on the scalp and areas of superficial peeling on the face, palms, soles, and genital region to Pityriasis rubra pilaris, OMIM:173200; Thick scales on the scalp and areas of superficial peeling on the face, palms, soles, and genital region
Peeling skin syndrome v1.3 CARD14 Arina Puzriakova Phenotypes for gene: CARD14 were changed from Pityriasis rubra pilaris, 173200; PRP; thick scales on the scalp and areas of superficial peeling on the face, palms, soles, and genital region to Pityriasis rubra pilaris, OMIM:173200; Thick scales on the scalp and areas of superficial peeling on the face, palms, soles, and genital region
Primary immunodeficiency or monogenic inflammatory bowel disease v2.522 TNFAIP3 Arina Puzriakova Phenotypes for gene: TNFAIP3 were changed from A20 deficiency; Autoinflammatory syndrome, familial, Behcet-like, 616744; Autoimmune lymphoproliferative syndrome; Arthralgia, mucosal ulcers, ocular inflammation; Autoinflammatory Disorders to Autoinflammatory syndrome, familial, Behcet-like, OMIM:616744; Autoimmune lymphoproliferative syndrome; Arthralgia, mucosal ulcers, ocular inflammation
COVID-19 research v1.110 TNFAIP3 Arina Puzriakova Phenotypes for gene: TNFAIP3 were changed from A20 deficiency; Autoimmune lymphoproliferative syndrome; Autoinflammatory Disorders; Autoinflammatory syndrome, familial, Behcet-like, 616744; Arthralgia, mucosal ulcers, ocular inflammation to Autoinflammatory syndrome, familial, Behcet-like, OMIM:616744; Autoimmune lymphoproliferative syndrome; Arthralgia, mucosal ulcers, ocular inflammation
Periodic fever syndromes v1.29 TNFAIP3 Arina Puzriakova Phenotypes for gene: TNFAIP3 were changed from Autoinflammatory syndrome, familial, Behcet-like; (AISBL) (616744) to Autoinflammatory syndrome, familial, Behcet-like, OMIM:616744
Rare genetic inflammatory skin disorders v1.49 TMEM173 Arina Puzriakova Phenotypes for gene: TMEM173 were changed from STING-ASSOCIATED VASCULOPATHY, INFANTILE-ONSET, OMIM:615934 to STING-associated vasculopathy, infantile-onset, OMIM:615934
COVID-19 research v1.109 TMEM173 Arina Puzriakova Phenotypes for gene: TMEM173 were changed from Autoinflammatory Disorders; Type 1 interferonopathies; Skin vasculopathy, inflammatory lung disease, systemic autoinflammation and ICC, FCL; STING-associated vasculopathy, infantile-onset 615934 to STING-associated vasculopathy, infantile-onset, OMIM:615934; Type 1 interferonopathies; Skin vasculopathy, inflammatory lung disease, systemic autoinflammation and ICC; Autoinflammatory Disorders
Primary immunodeficiency or monogenic inflammatory bowel disease v2.521 TMEM173 Arina Puzriakova Phenotypes for gene: TMEM173 were changed from STING-associated vasculopathy, infantile-onset 615934; Type 1 interferonopathies; Skin vasculopathy, inflammatory lung disease, systemic autoinflammation and ICC, FCL; Autoinflammatory Disorders to STING-associated vasculopathy, infantile-onset, OMIM:615934; Type 1 interferonopathies; Skin vasculopathy, inflammatory lung disease, systemic autoinflammation and ICC; Autoinflammatory Disorders
Primary immunodeficiency or monogenic inflammatory bowel disease v2.520 TNFRSF1A Arina Puzriakova Phenotypes for gene: TNFRSF1A were changed from Periodic fever, familial 142680; TNF-receptor associated periodic fever syndrome (TRAPS); Recurrent fever, serositis, rash, and ocular or joint inflammation; Autoinflammatory Disorders to Periodic fever, familial, OMIM:142680; TNF-receptor associated periodic fever syndrome (TRAPS); Recurrent fever, serositis, rash, and ocular or joint inflammation; Autoinflammatory Disorders
COVID-19 research v1.108 TNFRSF1A Arina Puzriakova Phenotypes for gene: TNFRSF1A were changed from Periodic fever, familial 142680; TNF-receptor associated periodic fever syndrome (TRAPS); Recurrent fever, serositis, rash, and ocular or joint inflammation; Autoinflammatory Disorders to Periodic fever, familial, OMIM:142680; TNF-receptor associated periodic fever syndrome (TRAPS); Recurrent fever, serositis, rash, and ocular or joint inflammation; Autoinflammatory Disorders
Familial Meniere Disease v1.3 TNFRSF1A Arina Puzriakova Phenotypes for gene: TNFRSF1A were changed from to Periodic fever, familial, OMIM:142680
Periodic fever syndromes v1.28 TNFRSF1A Arina Puzriakova Phenotypes for gene: TNFRSF1A were changed from Hereditary Periodic Fever Syndromes; Periodic fever, familial, 142680 to Periodic fever, familial, OMIM:142680
Hypogonadotropic hypogonadism v1.34 SLC29A3 Arina Puzriakova Phenotypes for gene: SLC29A3 were changed from Histiocytosis-lymphadenopathy plus syndrome, 602782 to Histiocytosis-lymphadenopathy plus syndrome, OMIM:602782
COVID-19 research v1.107 SLC29A3 Arina Puzriakova Phenotypes for gene: SLC29A3 were changed from Other autoinflammatory diseases with known genetic defect; Hyperpigmentation hypertrichosis, histiocytosis-lymphadenopathy plus syndrome; Autoinflammatory Disorders; Histiocytosis-lymphadenopathy plus syndrome 602782 to Histiocytosis-lymphadenopathy plus syndrome, OMIM:602782; Hyperpigmentation hypertrichosis, histiocytosis-lymphadenopathy plus syndrome; Autoinflammatory Disorders
Diabetes with additional phenotypes suggestive of a monogenic aetiology v1.65 SLC29A3 Arina Puzriakova Phenotypes for gene: SLC29A3 were changed from Pigmented hypertrichotic dermatosis with insulin-dependent diabetes (PHID) syndrome to Histiocytosis-lymphadenopathy plus syndrome, OMIM:602782; Pigmented hypertrichotic dermatosis with insulin-dependent diabetes (PHID) syndrome
DDG2P v2.57 SH3BP2 Arina Puzriakova Phenotypes for gene: SH3BP2 were changed from Cherubism to Cherubism, OMIM:118400
Skeletal dysplasia v2.167 SH3BP2 Arina Puzriakova Phenotypes for gene: SH3BP2 were changed from Cherubism 118400 to Cherubism, OMIM:118400
COVID-19 research v1.106 SH3BP2 Arina Puzriakova Phenotypes for gene: SH3BP2 were changed from Other autoinflammatory diseases with known genetic defect; Autoinflammatory Disorders; Bone degeneration in jaws; Cherubism 118400 to Cherubism, OMIM:118400; Autoinflammatory Disorders
Primary immunodeficiency or monogenic inflammatory bowel disease v2.519 SH3BP2 Arina Puzriakova Phenotypes for gene: SH3BP2 were changed from Other autoinflammatory diseases with known genetic defect; Bone degeneration in jaws; Cherubism 118400; Autoinflammatory Disorders to Cherubism, OMIM:118400; Autoinflammatory Disorders
Likely inborn error of metabolism v2.215 RBCK1 Arina Puzriakova Phenotypes for gene: RBCK1 were changed from Polyglucosan body myopathy 1 with or without immunodeficiency 615895 to Polyglucosan body myopathy 1 with or without immunodeficiency, OMIM:615895
Undiagnosed metabolic disorders v1.505 RBCK1 Arina Puzriakova Phenotypes for gene: RBCK1 were changed from Polyglucosan body myopathy 1 with or without immunodeficiency 615895 to Polyglucosan body myopathy 1 with or without immunodeficiency, OMIM:615895
Congenital myopathy v2.69 RBCK1 Arina Puzriakova Phenotypes for gene: RBCK1 were changed from Polyglucosan body myopathy, early-onset, with or without immunodeficiency, 615895 to Polyglucosan body myopathy 1 with or without immunodeficiency, OMIM:615895
Arthrogryposis v3.146 RBCK1 Arina Puzriakova Phenotypes for gene: RBCK1 were changed from Polyglucosan body myopathy, early-onset, with or without immunodeficiency, 615895 to Polyglucosan body myopathy 1 with or without immunodeficiency, OMIM:615895
Rhabdomyolysis and metabolic muscle disorders v1.60 RBCK1 Arina Puzriakova Phenotypes for gene: RBCK1 were changed from Polyglucosan body myopathy 1 with or without immunodeficiency 615895 to Polyglucosan body myopathy 1 with or without immunodeficiency, OMIM:615895
Primary immunodeficiency or monogenic inflammatory bowel disease v2.518 RBCK1 Arina Puzriakova Phenotypes for gene: RBCK1 were changed from Polyglucosan body myopathy, early-onset, with or without immunodeficiency 615895; Other autoinflammatory diseases with known genetic defect; HOIL1 deficiency; Bacterial infections, autoinflammation, amylopectinosis; Combined immunodeficiencies with associated or syndromic features to Polyglucosan body myopathy 1 with or without immunodeficiency, OMIM:615895; Bacterial infections, autoinflammation, amylopectinosis; Combined immunodeficiencies with associated or syndromic features
COVID-19 research v1.105 RBCK1 Arina Puzriakova Phenotypes for gene: RBCK1 were changed from Other autoinflammatory diseases with known genetic defect; HOIL1 deficiency; Polyglucosan body myopathy, early-onset, with or without immunodeficiency 615895; Bacterial infections, autoinflammation, amylopectinosis; Combined immunodeficiencies with associated or syndromic features to Polyglucosan body myopathy 1 with or without immunodeficiency, OMIM:615895; Bacterial infections, autoinflammation, amylopectinosis; Combined immunodeficiencies with associated or syndromic features
Pituitary hormone deficiency v2.11 PSTPIP1 Arina Puzriakova Phenotypes for gene: PSTPIP1 were changed from Pyogenic sterile arthritis, pyoderma gangrenosum, and acne (604416); Holoprosencephaly to Pyogenic sterile arthritis, pyoderma gangrenosum, and acne, OMIM:604416
Primary immunodeficiency or monogenic inflammatory bowel disease v2.517 PSTPIP1 Arina Puzriakova Phenotypes for gene: PSTPIP1 were changed from Pyogenic sterile arthritis, pyoderma gangrenosum, and acne 604416; Proline/serine/threonine phosphatase-interacting protein 1 deficiency (PSTPIP1); PAPA syndrome; Hyperzincaemia hypercalprotectinaemia; Destructive arthritis, inflammatory skin rash, myositis; Autoinflammatory Disorders to Pyogenic sterile arthritis, pyoderma gangrenosum, and acne, OMIM:604416; Destructive arthritis, inflammatory skin rash, myositis; Hyperzincaemia hypercalprotectinaemia; Autoinflammatory Disorders
COVID-19 research v1.104 PSTPIP1 Arina Puzriakova Phenotypes for gene: PSTPIP1 were changed from Pyogenic sterile arthritis, pyoderma gangrenosum, and acne 604416; Destructive arthritis, inflammatory skin rash, myositis; Hyperzincaemia hypercalprotectinaemia; Autoinflammatory Disorders; Proline/serine/threonine phosphatase-interacting protein 1 deficiency (PSTPIP1); PAPA syndrome to Pyogenic sterile arthritis, pyoderma gangrenosum, and acne, OMIM:604416; Destructive arthritis, inflammatory skin rash, myositis; Hyperzincaemia hypercalprotectinaemia; Autoinflammatory Disorders
Generalised pustular psoriasis v1.11 PSTPIP1 Arina Puzriakova Phenotypes for gene: PSTPIP1 were changed from Pyogenic sterile arthritis, pyoderma gangrenosum, and acne 604416 to Pyogenic sterile arthritis, pyoderma gangrenosum, and acne, OMIM:604416
Periodic fever syndromes v1.27 PSTPIP1 Arina Puzriakova Phenotypes for gene: PSTPIP1 were changed from Hereditary Periodic Fever Syndromes; PAPA syndrome; Pyogenic sterile arthritis, pyoderma gangrenosum, and acne, 604416 to Pyogenic sterile arthritis, pyoderma gangrenosum, and acne, OMIM:604416
Familial hidradenitis suppurativa v1.3 PSTPIP1 Arina Puzriakova Phenotypes for gene: PSTPIP1 were changed from pyoderma gangrenosum, acne, and Hidradenitis suppurativa (PASH syndrome); pyoderma gangrenosum, acne, pyogenic arthritis, and Hidradenitis suppurativa (PAPASH syndrome); Pyogenic sterile arthritis, pyoderma gangrenosum, and acne, 604416 (PAPA syndrome) to Pyogenic sterile arthritis, pyoderma gangrenosum, and acne, OMIM:604416
Intellectual disability v3.1489 PSMB8 Arina Puzriakova Phenotypes for gene: PSMB8 were changed from Autoinflammation, lipodystrophy, and dermatosis syndrome, 256040 to Proteasome-associated autoinflammatory syndrome 1 and digenic forms, OMIM:256040
Early onset or syndromic epilepsy v2.484 PSMB8 Arina Puzriakova Phenotypes for gene: PSMB8 were changed from Autoinflammation, lipodystrophy, and dermatosis syndrome 256040 to Proteasome-associated autoinflammatory syndrome 1 and digenic forms, OMIM:256040
Cytopenia - NOT Fanconi anaemia v1.51 PSMB8 Arina Puzriakova Phenotypes for gene: PSMB8 were changed from Proteasome-associated autoinflammatory syndrome 1 and digenic forms, 256040 to Proteasome-associated autoinflammatory syndrome 1 and digenic forms, OMIM:256040
Fetal anomalies v1.825 PSMB8 Arina Puzriakova Phenotypes for gene: PSMB8 were changed from NAKAJO SYNDROME to Proteasome-associated autoinflammatory syndrome 1 and digenic forms, OMIM:256040
Monogenic diabetes v2.44 PSMB8 Arina Puzriakova Phenotypes for gene: PSMB8 were changed from Autoinflammation, lipodystrophy, and dermatosis syndrome, 256040 to Proteasome-associated autoinflammatory syndrome 1 and digenic forms, OMIM:256040
Insulin resistance (including lipodystrophy) v1.14 PSMB8 Arina Puzriakova Phenotypes for gene: PSMB8 were changed from Autoinflammation, lipodystrophy, and dermatosis syndrome, 256040 to Proteasome-associated autoinflammatory syndrome 1 and digenic forms, OMIM:256040; Autoinflammation, lipodystrophy, and dermatosis syndrome
Primary immunodeficiency or monogenic inflammatory bowel disease v2.516 PSMB8 Arina Puzriakova Phenotypes for gene: PSMB8 were changed from Autoinflammation, lipodystrophy, and dermatosis syndrome 256040; Other autoinflammatory diseases with known genetic defect; CANDLE syndrome; chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome (CANDLE); Contractures, panniculitis, ICC, fevers; Autoinflammatory Disorders to Proteasome-associated autoinflammatory syndrome 1 and digenic forms, OMIM:256040; Autoinflammation, lipodystrophy, and dermatosis syndrome; Contractures, panniculitis, ICC, fevers; Autoinflammatory Disorders; CANDLE syndrome
COVID-19 research v1.103 PSMB8 Arina Puzriakova Phenotypes for gene: PSMB8 were changed from Other autoinflammatory diseases with known genetic defect; chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome (CANDLE); Contractures, panniculitis, ICC, fevers; Autoinflammatory Disorders; Autoinflammation, lipodystrophy, and dermatosis syndrome 256040; CANDLE syndrome to Proteasome-associated autoinflammatory syndrome 1 and digenic forms, OMIM:256040; Autoinflammation, lipodystrophy, and dermatosis syndrome; Contractures, panniculitis, ICC, fevers; Autoinflammatory Disorders; CANDLE syndrome
Periodic fever syndromes v1.26 PSMB8 Arina Puzriakova Phenotypes for gene: PSMB8 were changed from Autoinflammation, lipodystrophy, and dermatosis syndrome 256040 (Joint contractures, muscle atrophy, microcytic anemia, and panniculitis-induced lipodystrophy (JMP syndrome) and chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE syndrome)) to Proteasome-associated autoinflammatory syndrome 1 and digenic forms, OMIM:256040; Autoinflammation, lipodystrophy, and dermatosis syndrome
Gastrointestinal epithelial barrier disorders v1.69 PLCG2 Arina Puzriakova Phenotypes for gene: PLCG2 were changed from Inflammatory Bowel Disease (Very Early Onset) to Autoinflammation, antibody deficiency, and immune dysregulation syndrome, OMIM:614878
Infantile enterocolitis & monogenic inflammatory bowel disease v1.36 PLCG2 Arina Puzriakova Phenotypes for gene: PLCG2 were changed from Phospholipase C_2 defects; Autoinflammation, antibody deficiency, and immune dysregulation syndrome 614878 to Autoinflammation, antibody deficiency, and immune dysregulation syndrome, OMIM:614878
COVID-19 research v1.102 PLCG2 Arina Puzriakova Phenotypes for gene: PLCG2 were changed from Other autoinflammatory diseases with known genetic defect; Cold urticaria hypogammaglobulinemia, autoinflammation; Familial cold autoinflammatory syndrome 3 614468; Familial cold autoinflammatory syndrome 3; Autoinflammatory Disorders; Hypogammaglobulinaemia, cold induced urticaria, autoinflammatory; Autoinflammation, antibody deficiency, and immune dysregulation syndrome 614878 to Autoinflammation, antibody deficiency, and immune dysregulation syndrome, OMIM:614878; Familial cold autoinflammatory syndrome 3, OMIM:614468; Hypogammaglobulinaemia, cold induced urticaria, autoinflammatory
Primary immunodeficiency or monogenic inflammatory bowel disease v2.515 PLCG2 Arina Puzriakova Phenotypes for gene: PLCG2 were changed from Autoinflammation, antibody deficiency, and immune dysregulation syndrome 614878; Familial cold autoinflammatory syndrome 3 614468; Hypogammaglobulinaemia, cold induced urticaria, autoinflammatory; Familial cold autoinflammatory syndrome 3; Other autoinflammatory diseases with known genetic defect; Cold urticaria hypogammaglobulinemia, autoinflammation; Autoinflammatory Disorders to Autoinflammation, antibody deficiency, and immune dysregulation syndrome, OMIM:614878; Familial cold autoinflammatory syndrome 3, OMIM:614468; Hypogammaglobulinaemia, cold induced urticaria, autoinflammatory
DDG2P v2.56 PLCG2 Arina Puzriakova Phenotypes for gene: PLCG2 were changed from FAMILIAL COLD AUTOINFLAMMATORY SYNDROME 3 614468; AUTOINFLAMMATION, ANTIBODY DEFICIENCY, AND IMMUNE DYSREGULATION, PLCG2-ASSOCIATED 614878 to Autoinflammation, antibody deficiency, and immune dysregulation syndrome, OMIM:614878; Familial cold autoinflammatory syndrome 3, OMIM:614468
Intellectual disability v3.1488 OTULIN Arina Puzriakova Phenotypes for gene: OTULIN were changed from Otulin-related auto inflammatory syndrome (ORAS) to Autoinflammation, panniculitis, and dermatosis syndrome, OMIM:617099
Fetal anomalies v1.824 OTULIN Arina Puzriakova Phenotypes for gene: OTULIN were changed from Otulin-related auto inflammatory syndrome to Autoinflammation, panniculitis, and dermatosis syndrome, OMIM:617099
Primary immunodeficiency or monogenic inflammatory bowel disease v2.514 OTULIN Arina Puzriakova Phenotypes for gene: OTULIN were changed from Autoinflammation, panniculitis, and dermatosis syndrome, 617099; Fever, diarrhea , dermatitis; Autoinflammatory Disorders to Autoinflammation, panniculitis, and dermatosis syndrome, OMIM:617099; Fever, diarrhoea, dermatitis; Autoinflammatory Disorders
COVID-19 research v1.101 OTULIN Arina Puzriakova Phenotypes for gene: OTULIN were changed from Autoinflammation, panniculitis, and dermatosis syndrome, 617099; Fever, diarrhea , dermatitis; Autoinflammatory Disorders to Autoinflammation, panniculitis, and dermatosis syndrome, OMIM:617099; Fever, diarrhoea, dermatitis; Autoinflammatory Disorders
Gastrointestinal epithelial barrier disorders v1.68 OTULIN Arina Puzriakova Phenotypes for gene: OTULIN were changed from to Autoinflammation, panniculitis, and dermatosis syndrome, OMIM:617099
Infantile enterocolitis & monogenic inflammatory bowel disease v1.35 OTULIN Arina Puzriakova Phenotypes for gene: OTULIN were changed from Autoinflammation, panniculitis, and dermatosis syndrome, 617099; AIPDS to Autoinflammation, panniculitis, and dermatosis syndrome, OMIM:617099
Periodic fever syndromes v1.25 OTULIN Arina Puzriakova Phenotypes for gene: OTULIN were changed from Autoinflammation, panniculitis, and dermatosis syndrome (AIPDS) (617099); Otulin-related autoinflammatry syndrome (ORAS) to Autoinflammation, panniculitis, and dermatosis syndrome, OMIM:617099
Mosaic skin disorders - deep sequencing v1.20 NOD2 Arina Puzriakova Phenotypes for gene: NOD2 were changed from Blau syndrome to Blau syndrome, OMIM:186580
Primary immunodeficiency or monogenic inflammatory bowel disease v2.513 NOD2 Arina Puzriakova Phenotypes for gene: NOD2 were changed from Blau syndrome 186580; Caspase recruitment domain-containing protein 15 deficiency (CARD15); Uveitis, granulomatous synovitis, camptodactyly, rash and cranial neuropathies, 30% develop Crohn colitis; Autoinflammatory Disorders to Blau syndrome, OMIM:186580; {Inflammatory bowel disease 1, Crohn disease}, OMIM:266600; {Yao syndrome}, OMIM:617321
COVID-19 research v1.100 NOD2 Arina Puzriakova Phenotypes for gene: NOD2 were changed from Blau syndrome 186580; Uveitis, granulomatous synovitis, camptodactyly, rash and cranial neuropathies, 30% develop Crohn colitis; Autoinflammatory Disorders; Caspase recruitment domain-containing protein 15 deficiency (CARD15) to Blau syndrome, OMIM:186580; {Inflammatory bowel disease 1, Crohn disease}, OMIM:266600; {Yao syndrome}, OMIM:617321
Gastrointestinal epithelial barrier disorders v1.67 NOD2 Arina Puzriakova Phenotypes for gene: NOD2 were changed from {Inflammatory bowel disease 1, Crohn disease}; Crohn disease; Crohn Disease to {Inflammatory bowel disease 1, Crohn disease}, OMIM:266600; {Yao syndrome}, OMIM:617321
Periodic fever syndromes v1.24 NOD2 Arina Puzriakova Phenotypes for gene: NOD2 were changed from Blau syndrome, 186580 to Blau syndrome, OMIM:186580
Infantile enterocolitis & monogenic inflammatory bowel disease v1.34 NOD2 Arina Puzriakova Phenotypes for gene: NOD2 were changed from {Inflammatory bowel disease 1, Crohn disease} 266600; {Yao syndrome} 617321 to {Inflammatory bowel disease 1, Crohn disease}, OMIM:266600; {Yao syndrome}, OMIM:617321
Proteinuric renal disease v2.64 NLRP3 Arina Puzriakova Mode of inheritance for gene: NLRP3 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v3.1487 NLRP3 Arina Puzriakova Phenotypes for gene: NLRP3 were changed from Cold-induced autoinflammatory syndrome, familial, 120100Muckle-Wells syndrome, 191900CINCA syndrome, 607115 to CINCA syndrome, OMIM:607115
Monogenic hearing loss v2.216 NLRP3 Arina Puzriakova Phenotypes for gene: NLRP3 were changed from Cold-induced autoinflammatory syndrome, familial, 120100; Coldinducedautoinflammatorysyndrome,familial,120100MuckleWellssyndrome,191900CINCAsyndrome,607115 to CINCA syndrome, OMIM:607115; Deafness, autosomal dominant 34, with or without inflammation, OMIM:617772; Muckle-Wells syndrome, OMIM:191900
Monogenic hearing loss v2.215 NLRP3 Arina Puzriakova Mode of inheritance for gene: NLRP3 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Skeletal dysplasia v2.166 NLRP3 Arina Puzriakova Phenotypes for gene: NLRP3 were changed from Chronic infantile neurologic cutaneous articular syndrome (CINA) - 607115; CINCA (Infantile-onset multisystem inflammatory disease) 607115 to CINCA syndrome, OMIM:607115
Proteinuric renal disease v2.63 NLRP3 Arina Puzriakova Phenotypes for gene: NLRP3 were changed from SRNS to Muckle-Wells syndrome, OMIM:191900; Renal amyloidosis
Hereditary systemic amyloidosis v1.12 NLRP3 Arina Puzriakova Phenotypes for gene: NLRP3 were changed from Muckle-Wells syndrome, 191900; AA amyloidosis; renal amyloidosis to Muckle-Wells syndrome, OMIM:191900; Renal amyloidosis
Rare genetic inflammatory skin disorders v1.48 NLRP3 Arina Puzriakova Phenotypes for gene: NLRP3 were changed from CINCA SYNDROME, OMIM:607115 to CINCA syndrome, OMIM:607115; Muckle-Wells syndrome, OMIM:191900
Periodic fever syndromes v1.23 NLRP3 Arina Puzriakova Phenotypes for gene: NLRP3 were changed from Hereditary Periodic Fever Syndromes; CINCA syndrome (NOMID), 607115; Familial cold-induced inflammatory syndrome 1 (FCAS), 120100; Muckle-Wells syndrome (MWS), 191900 to CINCA syndrome, OMIM:607115; Deafness, autosomal dominant 34, with or without inflammation, OMIM:617772; Familial cold inflammatory syndrome 1, OMIM:120100; Muckle-Wells syndrome, OMIM:191900
Primary immunodeficiency or monogenic inflammatory bowel disease v2.512 NLRP3 Arina Puzriakova Phenotypes for gene: NLRP3 were changed from CINCA syndrome 607115; Muckle-Wells syndrome 191900; Familial cold autoinflammatory syndrome 1 120100; Deafness, autosomal dominant 34, with or without inflammation 617772; Non-pruritic urticaria, arthritis, chills, fever and leukocytosis after cold exposure; Autoinflammatory Disorders; Neonatal onset rash, chronic meningitis, and arthropathy with fever and inflammation; Urticaria, SNHL, amyloidosis to CINCA syndrome, OMIM:607115; Deafness, autosomal dominant 34, with or without inflammation, OMIM:617772; Familial cold inflammatory syndrome 1, OMIM:120100; Muckle-Wells syndrome, OMIM:191900
COVID-19 research v1.99 NLRP3 Arina Puzriakova Phenotypes for gene: NLRP3 were changed from CINCA syndrome 607115; Non-pruritic urticaria, arthritis, chills, fever and leukocytosis after cold exposure; Neonatal onset rash, chronic meningitis, and arthropathy with fever and inflammation; Urticaria, SNHL, amyloidosis; Muckle-Wells syndrome 191900; Autoinflammatory Disorders; Familial cold autoinflammatory syndrome 1 120100; Deafness, autosomal dominant 34, with or without inflammation 617772 to CINCA syndrome, OMIM:607115; Deafness, autosomal dominant 34, with or without inflammation, OMIM:617772; Familial cold inflammatory syndrome 1, OMIM:120100; Muckle-Wells syndrome, OMIM:191900
COVID-19 research v1.98 NLRP12 Arina Puzriakova Phenotypes for gene: NLRP12 were changed from Autoinflammatory Disorders; Non-pruritic urticaria, arthritis, chills, fever and leukocytosis after cold exposure.; preterm premature rupture of membranes (PPROM); Familial cold autoinflammatory syndrome 2, 611762 to Familial cold autoinflammatory syndrome 2, OMIM:611762; Non-pruritic urticaria, arthritis, chills, fever and leukocytosis after cold exposure; Preterm premature rupture of membranes (PPROM); Autoinflammatory Disorders
Primary immunodeficiency or monogenic inflammatory bowel disease v2.511 NLRP12 Arina Puzriakova Phenotypes for gene: NLRP12 were changed from Familial cold autoinflammatory syndrome 2, 611762; preterm premature rupture of membranes (PPROM); Non-pruritic urticaria, arthritis, chills, fever and leukocytosis after cold exposure.; Autoinflammatory Disorders to Familial cold autoinflammatory syndrome 2, OMIM:611762; Non-pruritic urticaria, arthritis, chills, fever and leukocytosis after cold exposure; Preterm premature rupture of membranes (PPROM); Autoinflammatory Disorders
Periodic fever syndromes v1.22 NLRP12 Arina Puzriakova Phenotypes for gene: NLRP12 were changed from Familial cold autoinflammatory syndrome 2; 611762 to Familial cold autoinflammatory syndrome 2, OMIM:611762
COVID-19 research v1.97 NLRC4 Arina Puzriakova Phenotypes for gene: NLRC4 were changed from Autoinflammatory Disorders; Severe enterocolitis and macrophage activation syndrome; Autoinflammation with infantile enterocolitis 616050; ?Familial cold autoinflammatory syndrome 4 616115 to Autoinflammation with infantile enterocolitis, OMIM:616050; ?Familial cold autoinflammatory syndrome 4, OMIM:616115; Severe enterocolitis and macrophage activation syndrome; Autoinflammatory Disorders
Primary immunodeficiency or monogenic inflammatory bowel disease v2.510 NLRC4 Arina Puzriakova Phenotypes for gene: NLRC4 were changed from ?Familial cold autoinflammatory syndrome 4 616115; Autoinflammation with infantile enterocolitis 616050; Severe enterocolitis and macrophage activation syndrome; Autoinflammatory Disorders to Autoinflammation with infantile enterocolitis, OMIM:616050; ?Familial cold autoinflammatory syndrome 4, OMIM:616115; Severe enterocolitis and macrophage activation syndrome; Autoinflammatory Disorders
Gastrointestinal epithelial barrier disorders v1.66 NLRC4 Arina Puzriakova Phenotypes for gene: NLRC4 were changed from Autoinflammation with infantile enterocolitis, 616050 to Autoinflammation with infantile enterocolitis, OMIM:616050
Periodic fever syndromes v1.21 NLRC4 Arina Puzriakova Phenotypes for gene: NLRC4 were changed from ?Familial cold autoinflammatory syndrome 4 616115; Autoinflammation with infantile enterocolitis 616050 to Autoinflammation with infantile enterocolitis, OMIM:616050; ?Familial cold autoinflammatory syndrome 4, OMIM:616115
Primary immunodeficiency or monogenic inflammatory bowel disease v2.509 MVK Arina Puzriakova Phenotypes for gene: MVK were changed from Hyper-IgD syndrome 260920; Mevalonic aciduria 610377; Hyper IgD syndrome (MVK); Periodic fever and leukocytosis with high IgD levels; Autoinflammatory Disorders to Hyper-IgD syndrome, OMIM:260920; Mevalonic aciduria, OMIM:610377; Periodic fever and leukocytosis with high IgD levels; Autoinflammatory Disorders
Retinal disorders v2.242 MVK Arina Puzriakova Phenotypes for gene: MVK were changed from Hyper-IgD syndrome; Mevalonic aciduria; Non-syndromic RP to Hyper-IgD syndrome, OMIM:260920; Mevalonic aciduria, OMIM:610377
Intellectual disability v3.1486 MVK Arina Puzriakova Phenotypes for gene: MVK were changed from Mevalonic aciduria to Mevalonic aciduria, OMIM:610377
Hereditary ataxia with onset in adulthood v2.139 MVK Arina Puzriakova Phenotypes for gene: MVK were changed from Mevalonic aciduria 610377 to Mevalonic aciduria, OMIM:610377
Adult onset neurodegenerative disorder v2.259 MVK Arina Puzriakova Phenotypes for gene: MVK were changed from Mevalonic aciduria 610377 to Mevalonic aciduria, OMIM:610377
Hereditary ataxia v1.282 MVK Arina Puzriakova Phenotypes for gene: MVK were changed from Mevalonic aciduria 610377 to Mevalonic aciduria, OMIM:610377
Cholestasis v1.100 MVK Arina Puzriakova Phenotypes for gene: MVK were changed from Mevalonic aciduria, OMIM:610377, MONDO:0012481 to Mevalonic aciduria, OMIM:610377
Ataxia and cerebellar anomalies - narrow panel v2.281 MVK Arina Puzriakova Phenotypes for gene: MVK were changed from Mevalonic aciduria OMIM:610377; mevalonic aciduria MONDO:0012481 to Mevalonic aciduria, OMIM:610377
COVID-19 research v1.96 MVK Arina Puzriakova Phenotypes for gene: MVK were changed from Hyper-IgD syndrome 260920; Autoinflammatory Disorders; Hyper IgD syndrome (MVK); Mevalonic aciduria 610377; Periodic fever and leukocytosis with high IgD levels to Hyper-IgD syndrome, OMIM:260920; Mevalonic aciduria, OMIM:610377; Autoinflammatory Disorders; Periodic fever and leukocytosis with high IgD levels
Fetal hydrops v1.46 MVK Arina Puzriakova Phenotypes for gene: MVK were changed from Mevalonic aciduria, MIM#610377 to Mevalonic aciduria, OMIM:610377
Neonatal cholestasis v1.23 MVK Arina Puzriakova Phenotypes for gene: MVK were changed from Mevalonic aciduria 610377 to Mevalonic aciduria, OMIM:610377
Gastrointestinal epithelial barrier disorders v1.65 MVK Arina Puzriakova Phenotypes for gene: MVK were changed from Early Onset Inflammatory Bowel Disease; Hyper-IgD syndrome 260920; Mevalonic aciduria 610377 to Hyper-IgD syndrome, OMIM:260920; Mevalonic aciduria, OMIM:610377
Infantile enterocolitis & monogenic inflammatory bowel disease v1.33 MVK Arina Puzriakova Phenotypes for gene: MVK were changed from Hyper-IgD syndrome 260920; Mevalonic aciduria 610377 to Hyper-IgD syndrome, OMIM:260920; Mevalonic aciduria, OMIM:610377
Periodic fever syndromes v1.20 MVK Arina Puzriakova Phenotypes for gene: MVK were changed from Hereditary Periodic Fever Syndromes; Mevalonate kinase deficiency; Hyper-IgD syndrome, 260920; Mevalonic aciduria, 610377 to Hyper-IgD syndrome, OMIM:260920; Mevalonic aciduria, OMIM:610377
Likely inborn error of metabolism v2.214 MVK Arina Puzriakova Phenotypes for gene: MVK were changed from Hyper-IgD syndrome 260920; Mevalonic aciduria 610377; Porokeratosis 3, multiple types 175900 to Hyper-IgD syndrome, OMIM:260920; Mevalonic aciduria, OMIM:610377; Porokeratosis 3, multiple types, OMIM:175900
Undiagnosed metabolic disorders v1.504 MVK Arina Puzriakova Phenotypes for gene: MVK were changed from Hyper-IgD syndrome 260920; Mevalonic aciduria 610377; Porokeratosis 3, multiple types 175900 to Hyper-IgD syndrome, OMIM:260920; Mevalonic aciduria, OMIM:610377; Porokeratosis 3, multiple types, OMIM:175900
Mosaic skin disorders - deep sequencing v1.19 MVK Arina Puzriakova Phenotypes for gene: MVK were changed from Actinic porokeratosis; porokeratosis of Mibelli to Porokeratosis 3, multiple types, OMIM:175900
Palmoplantar keratodermas v1.10 MVK Arina Puzriakova Phenotypes for gene: MVK were changed from porokeratosis of Mibelli; Actinic porokeratosis to Porokeratosis 3, multiple types, OMIM:175900
Familial disseminated superficial actinic porokeratosis v1.2 MVK Arina Puzriakova Phenotypes for gene: MVK were changed from Porokeratosis 3, multiple types, 175900; Porokeratosis 3, Multiple Types; POROK3; DSAP1; POROKERATOSIS, DISSEMINATED SUPERFICIAL ACTINIC, 1; Porokeratosis 3, Disseminated Superficial Actinic Type to Porokeratosis 3, multiple types, OMIM:175900
Proteinuric renal disease v2.62 MEFV Arina Puzriakova Phenotypes for gene: MEFV were changed from Familial Mediterranean fever, AR #249100 to Familial Mediterranean fever, AD, OMIM:134610; Familial Mediterranean fever, AR, OMIM:249100
COVID-19 research v1.95 MEFV Arina Puzriakova Phenotypes for gene: MEFV were changed from Familial mediterranean fever defect; Recurrent fever, serositis and inflammation responsive to colchicine. Predisoposes to vasculitis and inflammatory bowel disease.; Autoinflammatory Disorders; Familial Mediterranean fever, AD 134610; Familial Mediterranean fever, AR 249100 to Familial Mediterranean fever, AD, OMIM:134610; Familial Mediterranean fever, AR, OMIM:249100; Neutrophilic dermatosis, acute febrile, OMIM:608068; Recurrent fever, serositis and inflammation responsive to colchicine; Predisposes to vasculitis and inflammatory bowel disease; Autoinflammatory Disorders
Primary immunodeficiency or monogenic inflammatory bowel disease v2.508 MEFV Arina Puzriakova Phenotypes for gene: MEFV were changed from Familial Mediterranean fever, AD 134610; Familial Mediterranean fever, AR 249100; Familial mediterranean fever defect; Recurrent fever, serositis and inflammation responsive to colchicine. Predisoposes to vasculitis and inflammatory bowel disease.; Autoinflammatory Disorders to Familial Mediterranean fever, AD, OMIM:134610; Familial Mediterranean fever, AR, OMIM:249100; Neutrophilic dermatosis, acute febrile, OMIM:608068; Recurrent fever, serositis and inflammation responsive to colchicine; Predisposes to vasculitis and inflammatory bowel disease; Autoinflammatory Disorders
Gastrointestinal epithelial barrier disorders v1.64 MEFV Arina Puzriakova Phenotypes for gene: MEFV were changed from Early Onset Inflammatory Bowel Disease; Familial Mediterranean fever, AD 134610; Familial Mediterranean fever, AR 249100 to Familial Mediterranean fever, AD, OMIM:134610; Familial Mediterranean fever, AR, OMIM:249100; Early Onset Inflammatory Bowel Disease
Infantile enterocolitis & monogenic inflammatory bowel disease v1.32 MEFV Arina Puzriakova Phenotypes for gene: MEFV were changed from Familial Mediterranean fever, AD 134610; Familial Mediterranean fever, AR 249100 to Familial Mediterranean fever, AD, OMIM:134610; Familial Mediterranean fever, AR, OMIM:249100
Periodic fever syndromes v1.19 MEFV Arina Puzriakova Phenotypes for gene: MEFV were changed from Hereditary Periodic Fever Syndromes; Familial Mediterranean Fever; Familial Mediterranean fever, AD, 134610; Familial Mediterranean fever, AR, 249100 to Familial Mediterranean fever, AD, OMIM:134610; Familial Mediterranean fever, AR, OMIM:249100; Neutrophilic dermatosis, acute febrile, OMIM:608068
Familial hidradenitis suppurativa v1.2 MEFV Arina Puzriakova Phenotypes for gene: MEFV were changed from Mediterranean fever with hidradenitis suppurativa; Familial Mediterranean fever, AD, 134610; Familial Mediterranean fever, AR, 249100 to Mediterranean fever with hidradenitis suppurativa; Familial Mediterranean fever, AD, OMIM:134610; Familial Mediterranean fever, AR, OMIM:249100
Skeletal dysplasia v2.165 LPIN2 Arina Puzriakova Phenotypes for gene: LPIN2 were changed from Majeed syndrome (Chronic recurrent multifocal osteomyelitis with congenital dyserythropoietic anemia) 609628 to Majeed syndrome, OMIM:609628; Chronic recurrent multifocal osteomyelitis with congenital dyserythropoietic anemia
Rare anaemia v1.32 LPIN2 Arina Puzriakova Phenotypes for gene: LPIN2 were changed from Majeed syndrome, 609628; Microcytic anemia; Congenital dyserythropoietic anemia; CDA; 609628 Majeed syndrome; Majeed syndrome; 609628 Microcytic anemia to Majeed syndrome, OMIM:609628; Microcytic anemia; Congenital dyserythropoietic anemia
Cytopenias and congenital anaemias v1.94 LPIN2 Arina Puzriakova Phenotypes for gene: LPIN2 were changed from Microcytic anemia; Congenital dyserythropoietic anemia; CDA; Majeed syndrome, 609628 to Majeed syndrome, OMIM:609628; Microcytic anemia; Congenital dyserythropoietic anemia
Primary immunodeficiency or monogenic inflammatory bowel disease v2.507 LPIN2 Arina Puzriakova Phenotypes for gene: LPIN2 were changed from Majeed syndrome 609628; Other autoinflammatory diseases with known genetic defect; Chronic recurrent multifocal osteomyelitis, transfusion-dependent anemia, cutaneous inflammatory disorders; Autoinflammatory Disorders to Majeed syndrome, OMIM:609628; Chronic recurrent multifocal osteomyelitis, transfusion-dependent anemia, cutaneous inflammatory disorders; Autoinflammatory Disorders
COVID-19 research v1.94 LPIN2 Arina Puzriakova Phenotypes for gene: LPIN2 were changed from Other autoinflammatory diseases with known genetic defect; Chronic recurrent multifocal osteomyelitis, transfusion-dependent anemia, cutaneous inflammatory disorders; Autoinflammatory Disorders; Majeed syndrome 609628 to Majeed syndrome, OMIM:609628; Chronic recurrent multifocal osteomyelitis, transfusion-dependent anemia, cutaneous inflammatory disorders; Autoinflammatory Disorders
Periodic fever syndromes v1.18 LPIN2 Arina Puzriakova Phenotypes for gene: LPIN2 were changed from Hereditary Periodic Fever Syndromes; Majeed syndrome, 609628 to Majeed syndrome, OMIM:609628
Generalised pustular psoriasis v1.10 IL36RN Arina Puzriakova Phenotypes for gene: IL36RN were changed from Psoriasis 14, pustular 614204 to Psoriasis 14, pustular, OMIM:614204
Primary immunodeficiency or monogenic inflammatory bowel disease v2.506 IL36RN Arina Puzriakova Phenotypes for gene: IL36RN were changed from Psoriasis 14, generalized pustular 614204; Other autoinflammatory diseases with known genetic defect; Pustular psoriasis; Autoinflammatory Disorders to Psoriasis 14, pustular, OMIM:614204; Autoinflammatory Disorders
Rare genetic inflammatory skin disorders v1.47 IL36RN Arina Puzriakova Phenotypes for gene: IL36RN were changed from PSORIASIS 14, PUSTULAR, OMIM:614204 to Psoriasis 14, pustular, OMIM:614204
COVID-19 research v1.93 IL36RN Arina Puzriakova Phenotypes for gene: IL36RN were changed from Other autoinflammatory diseases with known genetic defect; Psoriasis 14, generalized pustular 614204; Autoinflammatory Disorders; Pustular psoriasis to Psoriasis 14, pustular, OMIM:614204; Autoinflammatory Disorders
Periodic fever syndromes v1.17 IL36RN Arina Puzriakova Phenotypes for gene: IL36RN were changed from Psoriasis 14, pustular, 614204; DITRA; recurrent flares of pustular rash with fever to Psoriasis 14, pustular, OMIM:614204; Recurrent flares of pustular rash with fever
Rare genetic inflammatory skin disorders v1.46 IL1RN Arina Puzriakova Phenotypes for gene: IL1RN were changed from OSTEOMYELITIS, STERILE MULTIFOCAL, WITH PERIOSTITIS AND PUSTULOSIS, OMIM:612852 to Interleukin 1 receptor antagonist deficiency, OMIM:612852
COVID-19 research v1.92 IL1RN Arina Puzriakova Phenotypes for gene: IL1RN were changed from Other autoinflammatory diseases with known genetic defect; DIRA; Interleukin 1 receptor antagonist deficiency 612852; Autoinflammatory Disorders; sterile multifocal osteomyelitis, periostitis, and pustulosis; Neonatal onset of sterile multifocal osteomyelitis, periostitis and pustulosis. to Interleukin 1 receptor antagonist deficiency, OMIM:612852; Sterile multifocal osteomyelitis, periostitis, and pustulosis; DIRA; Autoinflammatory Disorders
Primary immunodeficiency or monogenic inflammatory bowel disease v2.505 IL1RN Arina Puzriakova Phenotypes for gene: IL1RN were changed from Interleukin 1 receptor antagonist deficiency 612852; sterile multifocal osteomyelitis, periostitis, and pustulosis; Other autoinflammatory diseases with known genetic defect; DIRA; Neonatal onset of sterile multifocal osteomyelitis, periostitis and pustulosis.; Autoinflammatory Disorders to Interleukin 1 receptor antagonist deficiency, OMIM:612852; Sterile multifocal osteomyelitis, periostitis, and pustulosis; DIRA; Autoinflammatory Disorders
Skeletal dysplasia v2.164 IL1RN Arina Puzriakova Phenotypes for gene: IL1RN were changed from Interleukin 1 receptor antagonist deficiency 612852; Interleukin 1 receptor antagonist deficiency 612852 to Interleukin 1 receptor antagonist deficiency, OMIM:612852
Diabetes with additional phenotypes suggestive of a monogenic aetiology v1.64 IL1RN Arina Puzriakova Phenotypes for gene: IL1RN were changed from {Gastric cancer risk after H. pylori infection}, 137215; {Microvascular complications of diabetes 4}, 612628; Interleukin 1 receptor antagonist deficiency, 612852; to {Microvascular complications of diabetes 4}, OMIM:612628
Periodic fever syndromes v1.16 IL1RN Arina Puzriakova Phenotypes for gene: IL1RN were changed from Interleukin 1 receptor antagonist deficiency, 612852; OMPP; DIRA syndrome; recurrent fever to Interleukin 1 receptor antagonist deficiency, OMIM:612852
Autoinflammatory disorders v0.0 Arina Puzriakova Added Panel Autoinflammatory disorders
Set panel types to: GMS Rare Disease
Early onset or syndromic epilepsy v2.483 SCN8A Helen Lord reviewed gene: SCN8A: Rating: GREEN; Mode of pathogenicity: None; Publications: 31625145; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Rare syndromic craniosynostosis or isolated multisuture synostosis v2.60 HNRNPK Helen Lord reviewed gene: HNRNPK: Rating: GREEN; Mode of pathogenicity: None; Publications: 32588992; Phenotypes: Au Kline syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Rare syndromic craniosynostosis or isolated multisuture synostosis v2.60 LTBP1 Helen Lord reviewed gene: LTBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33991472; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rare syndromic craniosynostosis or isolated multisuture synostosis v2.60 MASP1 Helen Lord reviewed gene: MASP1: Rating: AMBER; Mode of pathogenicity: None; Publications: 21258343, 7677137, 29168297; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rare syndromic craniosynostosis or isolated multisuture synostosis v2.60 MASP1 Helen Lord Deleted their review
Rare syndromic craniosynostosis or isolated multisuture synostosis v2.60 MASP1 Helen Lord commented on gene: MASP1
Rare syndromic craniosynostosis or isolated multisuture synostosis v2.60 ZNF462 Helen Lord reviewed gene: ZNF462: Rating: GREEN; Mode of pathogenicity: None; Publications: 28513610, 31361404; Phenotypes: Weiss Kruszka syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Rare syndromic craniosynostosis or isolated multisuture synostosis v2.60 CHD7 Helen Lord changed review comment from: Newborn with bicoronal synostosis in whom a de novo CHD7 variant was identified c.6157C>T p.(Arg2053*) - NGS in proband, sanger sequencing used to exclude variant from the parents.
Other features included choanal atresia, markedly asymmetric malformed ears, folded and clipped off helix and triangular concha, retrognathia, marked facial asymetry with left eye constantly closed and hypoplastic toenails. Heart ultrasound revealed a small ASD and ophthalmoplegic exam revealed left retinal coloboma and asymmetrically placed eyes. CHARGE syndrome was suspected in this patient. Of note, this variant has been reported previoulsy in the literature in indivdiuals with CHARGE syndrome and no craniosynostosis was noted.
In this paper they mention two other cases reporteD in the literature in 2019/2020 where craniosynostosis was reported alongside a CHARGE phenotype and LOF variants were detected:
Siakallis et al, 2019: 30498854 c.3106C>T p.(Arg1036*) - CHARGE phenotype as well as synostosis of the coronal, left lambdoid and squamous sutures.
Tonne et al 2020: 33288889 c.7593dup p.(Thr2532fs) - CHARGE phenotype as well as late-onset sagittal synostosis.

Mouse studies indicate that CHD7 has a relevant dosage dependent role in the development of several craniofacial tissues - conditional knock out models showing among other bone and cartialage defects, frontal bone dysplasia.
Zebrafish model of CHARGE - flattening of the head is observed.
Sources: Expert Review; to: Newborn with bicoronal synostosis in whom a de novo CHD7 variant was identified c.6157C>T p.(Arg2053*) - NGS in proband, sanger sequencing used to exclude variant from the parents.
Other features included choanal atresia, markedly asymmetric malformed ears, folded and clipped off helix and triangular concha, retrognathia, marked facial asymetry with left eye constantly closed and hypoplastic toenails. Heart ultrasound revealed a small ASD and ophthalmoplegic exam revealed left retinal coloboma and asymmetrically placed eyes. CHARGE syndrome was suspected in this patient. Of note, this variant has been reported previoulsy in the literature in indivdiuals with CHARGE syndrome and no craniosynostosis was noted.
In this paper they mention two other cases reporteD in the literature in 2019/2020 where craniosynostosis was reported alongside a CHARGE phenotype and LOF variants were detected:
Siakallis et al, 2019: 30498854 c.3106C>T p.(Arg1036*) - CHARGE phenotype as well as synostosis of the coronal, left lambdoid and squamous sutures.
Tonne et al 2020: 33288889 c.7593dup p.(Thr2532fs) - CHARGE phenotype as well as late-onset sagittal synostosis.

Mouse studies indicate that CHD7 has a relevant dosage dependent role in the development of several craniofacial tissues - conditional knock out models showing among other bone and cartialage defects, frontal bone dysplasia.
Zebrafish model of CHARGE - flattening of the head is observed.
Sources: Expert Review
Rare syndromic craniosynostosis or isolated multisuture synostosis v2.60 CHD7 Helen Lord changed review comment from: Newborn with bicoronal synostosis in whom a de novo CHD7 variant was identified c.6157C>T p.(Arg2053*) - NGS in proband, sanger sequencing used to exclude variant from the parents.
Other features included choanal atresia, markedly asymmetric malformed ears, folded and clipped off helix and triangular concha, retrognathia, marked facial asymetry with left eye constantly closed and hypoplastic toenails. Heart ultrasound revealed a small ASD and ophthalmoplegic exam revealed left retinal coloboma and asymmetrically placed eyes. CHARGE syndrome was suspected in this patient. Of note, this variant has been reported previoulsy in the literature in indivdiuals with CHARGE syndrome and no craniosynostosis was noted.
In this paper they mention two other cases reporteD in the literature in 2019/2020 where craniosynostosis was reported alongside a CHARGE phenotype and LOF variants were detected:
Siakallis et al, 2019: 30498854 c.3106C>T p.(Arg1036*) - CHARGE phenotype as well as synostosis of the coronal, left lambdoid and squamous sutures.
Tonne et al 2020: 33288889 c.7593dup p.(Thr2532fs) - CHARGE phenotype as well as late-onset sagittal synostosis.

Mouse studies indicate that CHD7 has a relevant dosage dependent role in the development of several craniofacial tissues - conditional knock out models showing among other bone and cartialage defects, frontal bone dysplasia.
Zebrafish model of CHARGE - flattening of the head is observed.
Sources: Expert Review; to: Newborn with bicoronal synostosis in whom a de novo CHD7 variant was identified c.6157C>T p.(Arg2053*) - NGS in proband, sanger sequencing used to exclude variant from the parents.
Other features included choanal atresia, markedly asymmetric malformed ears, folded and clipped off helix and triangular concha, retrognathia, marked facial asymetry with left eye constantly closed and hypoplastic toenails. Heart ultrasound revealed a small ASD and ophthalmoplegic exam revealed left retinal coloboma and asymmetrically placed eyes. CHARGE syndrome was suspected in this patient. Of note, this variant has been reported previoulsy in the literature in indivdiuals with CHARGE syndrome and no craniosynostosis was noted.
In this paper they mention two other cases reporteD in the literature in 2019/2020 where craniosynostosis was reported alongside a CHARGE phenotype and LOF variants were detected:
Siakallis et al, 2019: 30498854 c.3106C>T p.(Arg1036*) - CHARGE phenotype as well as synostosis of the coronal, left lambdoid and squamous sutures.
Tonne et al 2020: 33288889 c.7593dup p.(Thr2532fs) - CHARGE phenotype as well as late-onset sagittal synostosis.

Mouse studies indicate that CHD7 has a relevant dosage dependent role in the development of several craniofacial tissues - conditional knock out models showing among other bone and cartialage defects, frontal bone dysplasia.
Zebrafish model of CHARGE - flattening of the head is observed.
Sources: Expert Review
Intellectual disability v3.1485 MYO5B Arina Puzriakova Phenotypes for gene: MYO5B were changed from Microvillus inclusion disease, 251850 to Diarrhea 2, with microvillus atrophy, OMIM:251850
Fetal anomalies v1.823 MYO5B Arina Puzriakova Phenotypes for gene: MYO5B were changed from MICROVILLUS INCLUSION DISEASE to Diarrhea 2, with microvillus atrophy, OMIM:251850
Intestinal failure or congenital diarrhoea v1.44 MYO5B Arina Puzriakova Phenotypes for gene: MYO5B were changed from Microvillus inclusion disease, OMIM:251850 to Diarrhea 2, with microvillus atrophy, OMIM:251850
Cholestasis v1.99 MYO5B Arina Puzriakova Phenotypes for gene: MYO5B were changed from Microvillus inclusion disease, 251850; Cholestasis; MYO5B associated disease to Diarrhea 2, with microvillus atrophy, OMIM:251850
COVID-19 research v1.91 MYO5B Arina Puzriakova Phenotypes for gene: MYO5B were changed from Microvillus inclusion disease 251850 to Diarrhea 2, with microvillus atrophy, OMIM:251850
Neonatal cholestasis v1.22 MYO5B Arina Puzriakova Phenotypes for gene: MYO5B were changed from MYO5B associated disease; Cholestasis to Diarrhea 2, with microvillus atrophy, OMIM:251850
Gastrointestinal epithelial barrier disorders v1.63 MYO5B Arina Puzriakova Phenotypes for gene: MYO5B were changed from Microvillus inclusion disease 251850; Microvillus inclusion disease to Diarrhea 2, with microvillus atrophy, OMIM:251850
Primary immunodeficiency or monogenic inflammatory bowel disease v2.504 MYO5B Arina Puzriakova Phenotypes for gene: MYO5B were changed from Microvillus inclusion disease 251850 to Diarrhea 2, with microvillus atrophy, OMIM:251850
Retinal disorders v2.241 PAK2 Arina Puzriakova gene: PAK2 was added
gene: PAK2 was added to Retinal disorders. Sources: Literature
Mode of inheritance for gene: PAK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PAK2 were set to 33693784
Phenotypes for gene: PAK2 were set to Knobloch 2 syndrome
Review for gene: PAK2 was set to RED
Added comment: Antonarakis et al., 2021 (PMID: 33693784) reported two affected siblings from a non-consanguineous New Zealand family. Both had retinal detachment and interstitial parenchymal pulmonary changes on chest X-rays, but only one child had additional significant features such as cataract, posterior encephalocele, severe DD/ID with ASD, and epilepsy. WES revealed a heterozygous PAK2 variant (c.1303 G>A, p.Glu435Lys) in both individuals that apparently occurred de novo indicating parental germ-line mosaicism; however, mosaicism could not be detected by deep sequencing of blood parental DNA. Functional studies showed that the variant, located in the kinase domain, results in a partial loss of the kinase activity.
Sources: Literature
Likely inborn error of metabolism v2.213 PDK3 Arina Puzriakova Publications for gene: PDK3 were set to 27604308; 26801680; 28902413; 23297365
Mitochondrial disorders v2.80 PDK3 Arina Puzriakova Publications for gene: PDK3 were set to
Possible mitochondrial disorder - nuclear genes v1.63 PDK3 Arina Puzriakova Publications for gene: PDK3 were set to
Possible mitochondrial disorder - nuclear genes v1.62 PDK3 Arina Puzriakova reviewed gene: PDK3: Rating: ; Mode of pathogenicity: None; Publications: 23297365, 26801680, 27388934, 28902413, 32504000, 34387338; Phenotypes: Charcot-Marie-Tooth disease, X-linked dominant, 6, OMIM:300905; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mitochondrial disorders v2.79 PDK3 Arina Puzriakova reviewed gene: PDK3: Rating: ; Mode of pathogenicity: None; Publications: 23297365, 26801680, 27388934, 28902413, 32504000, 34387338; Phenotypes: Charcot-Marie-Tooth disease, X-linked dominant, 6, OMIM:300905; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mitochondrial disorders v2.79 PDK3 Arina Puzriakova Tag Q1_22_phenotype tag was added to gene: PDK3.
Possible mitochondrial disorder - nuclear genes v1.62 PDK3 Arina Puzriakova Tag Q1_22_phenotype tag was added to gene: PDK3.
Likely inborn error of metabolism v2.212 PDK3 Arina Puzriakova Tag Q1_22_phenotype tag was added to gene: PDK3.
Likely inborn error of metabolism v2.212 PDK3 Arina Puzriakova reviewed gene: PDK3: Rating: ; Mode of pathogenicity: None; Publications: 23297365, 26801680, 27388934, 28902413, 32504000, 34387338; Phenotypes: Charcot-Marie-Tooth disease, X-linked dominant, 6, OMIM:300905; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Hereditary neuropathy or pain disorder v1.80 PDK3 Arina Puzriakova edited their review of gene: PDK3: Changed rating: GREEN
Hereditary neuropathy or pain disorder v1.80 PDK3 Arina Puzriakova Publications for gene: PDK3 were set to 26801680; 23297365
Hereditary neuropathy or pain disorder v1.79 PDK3 Arina Puzriakova Tag Q1_22_rating tag was added to gene: PDK3.
Hereditary neuropathy or pain disorder v1.79 PDK3 Arina Puzriakova Classified gene: PDK3 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v1.79 PDK3 Arina Puzriakova Added comment: Comment on list classification: At least two variants in three unrelated families reported (founder effect ruled out), as well as functional analyses conducted in patient fibroblasts, cell lines, and animal model. This supports a rating upgrade on this panel from Amber to Green at the next GMS panel update (tagged).
Hereditary neuropathy or pain disorder v1.79 PDK3 Arina Puzriakova Gene: pdk3 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v1.78 PDK3 Arina Puzriakova reviewed gene: PDK3: Rating: ; Mode of pathogenicity: None; Publications: 34387338; Phenotypes: Charcot-Marie-Tooth disease, X-linked dominant, 6, OMIM:300905; Mode of inheritance: None
Mitochondrial disorders v2.79 PDK3 Arina Puzriakova Mode of inheritance for gene: PDK3 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)
Primary immunodeficiency or monogenic inflammatory bowel disease v2.503 AGR2 Arina Puzriakova Tag Q1_22_rating tag was added to gene: AGR2.
Primary ovarian insufficiency v1.63 KHDRBS1 Ivone Leong Classified gene: KHDRBS1 as Amber List (moderate evidence)
Primary ovarian insufficiency v1.63 KHDRBS1 Ivone Leong Added comment: Comment on list classification: This gene is not associated with a phenotype in OMIM or Gene2Phenotype.

PMID:28938739 describes 2 cases. There was no details given for the idiopathic POI case.

ClinVar ID: 929733: as there is no further information available about this case I am hesitant in including this as part of the case count.

PMID:29808484. As stated by Zornitza Stark (Australian Genomics), the variant detected in this paper is also not included in the case count.

As there is only 1 case and 1 animal model there is currently not enough evidence to support a gene-disease association. This gene has been given an Amber rating until more evidence is available.
Primary ovarian insufficiency v1.63 KHDRBS1 Ivone Leong Gene: khdrbs1 has been classified as Amber List (Moderate Evidence).
Primary ovarian insufficiency v1.62 KHDRBS1 Ivone Leong Tag watchlist tag was added to gene: KHDRBS1.
Retinal disorders v2.240 SSBP1 Sarah Leigh Tag Q1_22_MOI tag was added to gene: SSBP1.
Retinal disorders v2.240 SSBP1 Sarah Leigh reviewed gene: SSBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Optic neuropathy v2.56 SSBP1 Sarah Leigh changed review comment from: The moi for this gene could be changed to BOTH monoallelic and biallelic as PMID: 34905022 reports a case of SSBP1-disease with biallelic SSBP1 variants.; to: The moi for this gene should be changed to BOTH monoallelic and Biallelic as PMID: 34905022 & 3155024 report two cases of SSBP1-disease associated with biallelic SSBP1 variants. The variant c.380G>A p.(Arg127Gln)(MAF of 0.00004) was found with c.394A>G p.(Ile132Val)(PMID: 34905022), which had previously been found as a homozygote in a single case (PMID: 31550240).
Likely inborn error of metabolism v2.212 SSBP1 Sarah Leigh changed review comment from: Comment on mode of inheritance: The moi for this gene could be changed to BOTH monoallelic and Biallelic as PMID: 34905022 reports a case of SSBP1-disease with biallelic SSBP1 variants.; to: Comment on mode of inheritance: The moi for this gene should be changed to BOTH monoallelic and Biallelic as PMID: 34905022 & 3155024 report two cases of SSBP1-disease associated with biallelic SSBP1 variants. The variant c.380G>A p.(Arg127Gln)(MAF of 0.00004) was found with c.394A>G p.(Ile132Val)(PMID: 34905022), which had previously been found as a homozygote in a single case (PMID: 31550240).
Mitochondrial disorders v2.78 SSBP1 Sarah Leigh Tag Q1_22_MOI was removed from gene: SSBP1.
Mitochondrial disorders v2.78 SSBP1 Sarah Leigh edited their review of gene: SSBP1: Added comment: Associated with relevant phenotype in OMIM, but not associated with a phenotype in Gen2Phen.
SSBP1 is involved in mitochondrial biogenesis (PMID: 7789991) and variants in it are associated with mtDNA maintenance defects and mitochondrial disease. At least six heterozygous SSBP1 variants have been reported and two biallelic cases have also been reported; c.380G>A p.(Arg127Gln)(MAF of 0.00004) was found with c.394A>G p.(Ile132Val)(PMID: 34905022), which had previously been found as a homozygote in a single case (PMID: 31550240).; Changed rating: GREEN
Fetal anomalies v1.822 TLL1 Ivone Leong Tag Q1_22_rating tag was added to gene: TLL1.
Familial non syndromic congenital heart disease v1.71 TLL1 Ivone Leong Classified gene: TLL1 as Green List (high evidence)
Familial non syndromic congenital heart disease v1.71 TLL1 Ivone Leong Gene: tll1 has been classified as Green List (High Evidence).
Fetal anomalies v1.822 TLL1 Ivone Leong Entity copied from Familial non syndromic congenital heart disease v1.70
Fetal anomalies v1.822 TLL1 Ivone Leong gene: TLL1 was added
gene: TLL1 was added to Fetal anomalies. Sources: Expert Review Amber,Radboud University Medical Center, Nijmegen,Literature
Mode of inheritance for gene: TLL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TLL1 were set to 18830233; 30538173; 27418595; 10331975; 31570783
Phenotypes for gene: TLL1 were set to Atrial septal defect 6, OMIM:613087
Penetrance for gene: TLL1 were set to Complete
Familial non syndromic congenital heart disease v1.70 TLL1 Ivone Leong Classified gene: TLL1 as Amber List (moderate evidence)
Familial non syndromic congenital heart disease v1.70 TLL1 Ivone Leong Gene: tll1 has been classified as Amber List (Moderate Evidence).
Familial non syndromic congenital heart disease v1.69 TLL1 Ivone Leong Classified gene: TLL1 as Green List (high evidence)
Familial non syndromic congenital heart disease v1.69 TLL1 Ivone Leong Added comment: Comment on list classification: This gene is associated with a phenotype in OMIM and Gene2Phenotype (limited). There is now enough evidence to support a gene-disease association. This gene should be rated Green.
Familial non syndromic congenital heart disease v1.69 TLL1 Ivone Leong Gene: tll1 has been classified as Green List (High Evidence).
Mitochondrial disorders v2.78 SSBP1 Sarah Leigh Classified gene: SSBP1 as Amber List (moderate evidence)
Mitochondrial disorders v2.78 SSBP1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Mitochondrial disorders v2.78 SSBP1 Sarah Leigh Gene: ssbp1 has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v2.77 SSBP1 Sarah Leigh Tag Q1_22_rating tag was added to gene: SSBP1.
Tag Q1_22_MOI tag was added to gene: SSBP1.
Familial non syndromic congenital heart disease v1.68 TLL1 Ivone Leong Added comment: Comment on publications: PMID:10331975 is a mouse model. Homozygous mutantsw were embryonic lethal with developmental defects in the heart (incomplete formation of the interventricular septum and an abnormal and novel positioning of the heart and aorta).

PMID:31570783 describes an individual with atrial septal defect with a de novo splice site variant in TLL1. However, the patient also has a variant in NODAL.
Familial non syndromic congenital heart disease v1.68 TLL1 Ivone Leong Publications for gene: TLL1 were set to 18830233; 30538173; 27418595
Primary immunodeficiency or monogenic inflammatory bowel disease v2.503 AGR2 Arina Puzriakova Classified gene: AGR2 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v2.503 AGR2 Arina Puzriakova Added comment: Comment on list classification: New gene added by Dmitrijs Rots (RadboudUMC). This gene is not associated with a phenotype in OMIM or Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green.
Primary immunodeficiency or monogenic inflammatory bowel disease v2.503 AGR2 Arina Puzriakova Gene: agr2 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v2.502 AGR2 Arina Puzriakova Publications for gene: AGR2 were set to PMID: 34952832
Primary immunodeficiency or monogenic inflammatory bowel disease v2.501 AGR2 Arina Puzriakova Phenotypes for gene: AGR2 were changed from CF-like disorder to Cystic fibrosis-like syndrome
Optic neuropathy v2.56 SSBP1 Sarah Leigh reviewed gene: SSBP1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Optic neuropathy v2.56 SSBP1 Sarah Leigh Tag Q1_22_MOI tag was added to gene: SSBP1.
Likely inborn error of metabolism v2.212 SSBP1 Sarah Leigh Publications for gene: SSBP1 were set to 31298765; 31550240; 31550237; 30412255; 31479473; 31479473
Likely inborn error of metabolism v2.211 SSBP1 Sarah Leigh Added comment: Comment on mode of inheritance: The moi for this gene could be changed to BOTH monoallelic and Biallelic as PMID: 34905022 reports a case of SSBP1-disease with biallelic SSBP1 variants.
Likely inborn error of metabolism v2.211 SSBP1 Sarah Leigh Mode of inheritance for gene: SSBP1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Likely inborn error of metabolism v2.210 SSBP1 Sarah Leigh Tag Q1_22_MOI tag was added to gene: SSBP1.
Childhood onset hereditary spastic paraplegia v2.121 PI4KA Arina Puzriakova Tag Q1_22_phenotype tag was added to gene: PI4KA.
Mitochondrial disorders v2.77 SSBP1 Sarah Leigh Added comment: Comment on mode of inheritance: PMID: 34905022 reports a case of SSBP1-disease with biallelic SSBP1 variants.
Mitochondrial disorders v2.77 SSBP1 Sarah Leigh Mode of inheritance for gene: SSBP1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Childhood onset hereditary spastic paraplegia v2.121 PI4KA Arina Puzriakova Tag Q1_22_expert_review tag was added to gene: PI4KA.
Tag Q1_22_NHS_review tag was added to gene: PI4KA.
Mitochondrial disorders v2.76 SSBP1 Sarah Leigh Mode of inheritance for gene: SSBP1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Optic neuropathy v2.56 SSBP1 Sarah Leigh Phenotypes for gene: SSBP1 were changed from Optic atrophy 13 with retinal and foveal abnormalities, OMIM:165510; Autosomal dominant optic atrophy with variable retinal degeneration; Optic atrophy with retinal degeneration (+-systemic features) to Optic atrophy 13 with retinal and foveal abnormalities OMIM:165510
Likely inborn error of metabolism v2.210 SSBP1 Sarah Leigh Publications for gene: SSBP1 were set to 31298765
Optic neuropathy v2.55 SSBP1 Sarah Leigh Publications for gene: SSBP1 were set to 31298765; 31550240; 31550237; 30412255
Likely inborn error of metabolism v2.209 SSBP1 Sarah Leigh Phenotypes for gene: SSBP1 were changed from to Optic atrophy 13 with retinal and foveal abnormalities, OMIM:165510
Mitochondrial disorders v2.75 SSBP1 Sarah Leigh Phenotypes for gene: SSBP1 were changed from No OMIM phenotype to Optic atrophy 13 with retinal and foveal abnormalities, OMIM:165510
Mitochondrial disorders v2.74 SSBP1 Sarah Leigh Publications for gene: SSBP1 were set to 29182774
Retinal disorders v2.240 SSBP1 Sarah Leigh Publications for gene: SSBP1 were set to 31298765; 31479473; 31550237; 31550240
Familial non syndromic congenital heart disease v1.67 TLL1 Ivone Leong Phenotypes for gene: TLL1 were changed from Atrial septal defect 6 613087 to Atrial septal defect 6, OMIM:613087
Familial non syndromic congenital heart disease v1.66 TLL1 Ivone Leong Publications for gene: TLL1 were set to 18830233
Intestinal failure or congenital diarrhoea v1.43 AGR2 Ivone Leong Entity copied from Respiratory ciliopathies including non-CF bronchiectasis v1.53
Intestinal failure or congenital diarrhoea v1.43 AGR2 Ivone Leong gene: AGR2 was added
gene: AGR2 was added to Intestinal failure. Sources: Expert Review Amber,Literature
Q1_22_rating tags were added to gene: AGR2.
Mode of inheritance for gene: AGR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AGR2 were set to 34952832
Phenotypes for gene: AGR2 were set to Cystic fibrosis-like syndrome; chronic diarrhoea
Penetrance for gene: AGR2 were set to Complete
Respiratory ciliopathies including non-CF bronchiectasis v1.53 AGR2 Ivone Leong Tag Q1_22_rating tag was added to gene: AGR2.
Respiratory ciliopathies including non-CF bronchiectasis v1.53 AGR2 Ivone Leong Classified gene: AGR2 as Amber List (moderate evidence)
Respiratory ciliopathies including non-CF bronchiectasis v1.53 AGR2 Ivone Leong Added comment: Comment on list classification: New gene added by Dmitrijs Rots (RadboudUMC). This gene is not associated with a phenotype in OMIM or Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green.
Respiratory ciliopathies including non-CF bronchiectasis v1.53 AGR2 Ivone Leong Gene: agr2 has been classified as Amber List (Moderate Evidence).
Respiratory ciliopathies including non-CF bronchiectasis v1.52 AGR2 Ivone Leong Phenotypes for gene: AGR2 were changed from CF-like syndrome to Cystic fibrosis-like syndrome; chronic diarrhoea
Respiratory ciliopathies including non-CF bronchiectasis v1.51 AGR2 Ivone Leong Publications for gene: AGR2 were set to PMID: 34952832
Ataxia and cerebellar anomalies - narrow panel v2.280 PRDX3 Arina Puzriakova Entity copied from Hereditary ataxia - adult onset v2.138
Ataxia and cerebellar anomalies - narrow panel v2.280 PRDX3 Arina Puzriakova gene: PRDX3 was added
gene: PRDX3 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Amber,Literature
Q1_22_rating tags were added to gene: PRDX3.
Mode of inheritance for gene: PRDX3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRDX3 were set to 33889951
Phenotypes for gene: PRDX3 were set to Cerebellar ataxia (early onset, mild to moderate, progressive)
Hereditary ataxia with onset in adulthood v2.138 PRDX3 Arina Puzriakova Tag Q1_22_rating tag was added to gene: PRDX3.
Hereditary ataxia with onset in adulthood v2.138 PRDX3 Arina Puzriakova Classified gene: PRDX3 as Amber List (moderate evidence)
Hereditary ataxia with onset in adulthood v2.138 PRDX3 Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark. There is enough evidence to promote this gene to Green at the next GMS panel update.

Rebelo et al., 2021 (PMID: 33889951) reported five simplex families with biallelic variants in PRDX3 leading to complete loss of its encoded protein. Clinical presentation in all individuals predominantly consisted of gait and upper limb ataxia and cerebellar atrophy. Age of onset was at 13, 15, 21, 22 and 23 years of age. Pathogenicity supported by molecular studies using patient fibroblasts, cerebellar medulloblastoma cells and Drosophila.
Hereditary ataxia with onset in adulthood v2.138 PRDX3 Arina Puzriakova Gene: prdx3 has been classified as Amber List (Moderate Evidence).
Hereditary haemorrhagic telangiectasia v2.11 GDF2 Sarah Leigh Phenotypes for gene: GDF2 were changed from Telangiectasia, hereditary hemorrhagic, type 5 615506 to Telangiectasia, hereditary hemorrhagic, type 5 OMIM:615506; telangiectasia, hereditary hemorrhagic, type 5 MONDO:0014217
Primary immunodeficiency or monogenic inflammatory bowel disease v2.500 CARD10 Arina Puzriakova changed review comment from: Comment on list classification: New gene added by Zornitza Stark. Rating Red at present only a single family has been reported as affected by immunodeficiency with autoimmunity due to a homozygoys variant in this gene (PMID: 32238915); to: Comment on list classification: New gene added by Zornitza Stark. Rating Red as at present only a single family has been reported as affected by immunodeficiency with autoimmunity due to a homozygoys variant in this gene (PMID: 32238915)
Primary immunodeficiency or monogenic inflammatory bowel disease v2.500 CARD10 Arina Puzriakova Classified gene: CARD10 as Red List (low evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v2.500 CARD10 Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark. Rating Red at present only a single family has been reported as affected by immunodeficiency with autoimmunity due to a homozygoys variant in this gene (PMID: 32238915)
Primary immunodeficiency or monogenic inflammatory bowel disease v2.500 CARD10 Arina Puzriakova Gene: card10 has been classified as Red List (Low Evidence).
Hereditary haemorrhagic telangiectasia v2.10 GDF2 Sarah Leigh edited their review of gene: GDF2: Added comment: PMID: 34904380 reports a novel GDF2 variant (c.1282T>C, p.C428R) in three members of family displaying hereditary hemorrhagic telangiectasia (HHT) and pulmonary arteriovenous malformations. Functional studies support the delaterious effect of the variant in the normal cleavage of BMP9 proprotein, leading to an >2.5-fold lower level of the active mature dimer in the plasma of variant-positive family members in comparison to controls and lower levels of mature BMP9 from in vitro expression studies. There is phenotypic variability between patients carrying the same variant in HHT, and this is pronounced in the three cases reported in PMID: 34904380; although all of the cases in this familiy meet the Curaçao Criteria, the two non-proband cases are regarded as mild.; Changed rating: AMBER
Primary immunodeficiency or monogenic inflammatory bowel disease v2.499 CARD10 Arina Puzriakova Phenotypes for gene: CARD10 were changed from Immunodeficiency 89 and autoimmunity, MIM# 619632 to Immunodeficiency 89 and autoimmunity, OMIM:619632
Hereditary Erythrocytosis v1.44 PIEZO1 Arina Puzriakova Classified gene: PIEZO1 as Amber List (moderate evidence)
Hereditary Erythrocytosis v1.44 PIEZO1 Arina Puzriakova Added comment: Comment on list classification: New association with this phenotype identified by external reviewer, Dmitrijs Rots. Rating Amber but there is sufficient evidence to promote this gene to Green at the next GMS panel update.
Hereditary Erythrocytosis v1.44 PIEZO1 Arina Puzriakova Gene: piezo1 has been classified as Amber List (Moderate Evidence).
Hereditary Erythrocytosis v1.43 PIEZO1 Arina Puzriakova Tag Q1_22_rating tag was added to gene: PIEZO1.
Hereditary Erythrocytosis v1.43 PIEZO1 Arina Puzriakova reviewed gene: PIEZO1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33181827, 31298594, 30655378; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Erythrocytosis v1.43 PIEZO1 Arina Puzriakova Publications for gene: PIEZO1 were set to PMID: 33181827
Skeletal dysplasia v2.163 PRKG2 Arina Puzriakova Added comment: Comment on phenotypes: Added relevant phenotypes now listed in OMIM (MIM# 619636 and MIM# 619638)
Skeletal dysplasia v2.163 PRKG2 Arina Puzriakova Phenotypes for gene: PRKG2 were changed from acromesomelic dysplasia, MONDO:0019696; spondylometaphyseal dysplasia, MONDO:0016763 to Acromesomelic dysplasia 4, OMIM:619636; Spondylometaphyseal dysplasia, Pagnamenta type, OMIM:619638
Hereditary haemorrhagic telangiectasia v2.10 GDF2 Sarah Leigh Added comment: Comment on publications: 23972370 - 3 unrelated probands with no variants identified in ENG, ACVRL1, and SMAD4;27081547 - a variant of unknown significance in GDF2 was detected in one of 93 unrelated individuals clinically suspected to have HHT who previously tested negative for mutations in ENG, ACVRL1 and SMAD4;25674101 - review from the same authors as PMID:23972370
Hereditary haemorrhagic telangiectasia v2.10 GDF2 Sarah Leigh Publications for gene: GDF2 were set to 23972370 - 3 unrelated probands with no variants identified in ENG, ACVRL1, and SMAD4; 27081547 - a variant of unknown significance in GDF2 was detected in one of 93 unrelated individuals clinically suspected to have HHT who previously tested negative for mutations in ENG, ACVRL1 and SMAD4; 25674101 - review from the same authors as PMID:23972370; 32573726; 32669404; 33834622; https://doi.org/10.1164/ajrccm-conference.2020.201.1_MeetingAbstracts.A6356
Renal ciliopathies v1.45 DLG5 Arina Puzriakova Tag Q3_21_MOI tag was added to gene: DLG5.
Respiratory ciliopathies including non-CF bronchiectasis v1.50 AGR2 Dmitrijs Rots gene: AGR2 was added
gene: AGR2 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: Literature
Mode of inheritance for gene: AGR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AGR2 were set to PMID: 34952832
Phenotypes for gene: AGR2 were set to CF-like syndrome
Penetrance for gene: AGR2 were set to Complete
Review for gene: AGR2 was set to GREEN
Added comment: 13 individuals reported in PMID: 34952832 with Cystic fibrosis -like syndrome, including with respiratory infections, bronchiectasis etc. Ciliary abnormalities are reported, but authors suggest that they are likely secondary, similarly to CF.
Sources: Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v2.498 AGR2 Dmitrijs Rots gene: AGR2 was added
gene: AGR2 was added to Primary immunodeficiency. Sources: Literature
Mode of inheritance for gene: AGR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AGR2 were set to PMID: 34952832
Phenotypes for gene: AGR2 were set to CF-like disorder
Penetrance for gene: AGR2 were set to Complete
Review for gene: AGR2 was set to GREEN
Added comment: 13 individuals reported in PMID: 34952832 with Cystic Fibrosis like phenotype, including respiratory infections present in 13/13 individuals.
Sources: Literature
DDG2P v2.55 MYH6 Dmitrijs Rots reviewed gene: MYH6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
DDG2P v2.55 TERC Dmitrijs Rots reviewed gene: TERC: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
DDG2P v2.55 RMRP Dmitrijs Rots reviewed gene: RMRP: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
DDG2P v2.55 COL6A1 Dmitrijs Rots reviewed gene: COL6A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Bethlem myopathy, Ulrich myopathy; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
DDG2P v2.55 PMS2 Dmitrijs Rots changed review comment from: DD is not part of the phenotype. Red on ID list.; to: DD is not part of the phenotype. Red on ID list. Other MMR deficiency genes are not in the panel.
DDG2P v2.55 PMS2 Dmitrijs Rots reviewed gene: PMS2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
DDG2P v2.55 AR Dmitrijs Rots reviewed gene: AR: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinal and bulbar muscular atrophy, Androgen insensitivity syndrome; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Adult onset leukodystrophy v1.36 TPP2 Dmitrijs Rots edited their review of gene: TPP2: Changed rating: GREEN
Adult onset leukodystrophy v1.36 TPP2 Dmitrijs Rots changed review comment from: 14 individuals with "TRIANGLE" (TPPII-related immunodeficiency,
autoimmunity, and neurodevelopmental delay with impaired glycolysis
and lysosomal expansion) syndrome are summarized in 25414442, where 4/14 presented in adulthood with white matter leasions mimicking multiple sclerosis.
Sources: Literature; to: 14 individuals with "TRIANGLE" (TPPII-related immunodeficiency,
autoimmunity, and neurodevelopmental delay with impaired glycolysis
and lysosomal expansion) syndrome are summarized in 25414442, where 4/14 presented in adulthood with white matter leasions mimicking multiple sclerosis.
Should be rated green.
Sources: Literature
Adult onset leukodystrophy v1.36 TPP2 Dmitrijs Rots changed review comment from: 14 individuals with "TRIANGLE" (TPPII-related immunodeficiency,
autoimmunity, and neurodevelopmental delay with impaired glycolysis
and lysosomal expansion) syndrome are summarized in 25414442, where 4/14 presented in adulthood with white matter leasions mimicking multiple sclerosis.
Sources: Literature; to: 14 individuals with "TRIANGLE" (TPPII-related immunodeficiency,
autoimmunity, and neurodevelopmental delay with impaired glycolysis
and lysosomal expansion) syndrome are summarized in 25414442, where 4/14 presented in adulthood with white matter leasions mimicking multiple sclerosis.
Sources: Literature
Adult onset leukodystrophy v1.36 TPP2 Dmitrijs Rots gene: TPP2 was added
gene: TPP2 was added to White matter disorders - adult onset. Sources: Literature
Mode of inheritance for gene: TPP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TPP2 were set to PMID:25414442
Phenotypes for gene: TPP2 were set to White matter abnormalities; autoimmunity; immunodefficiency; developmental delay
Added comment: 14 individuals with "TRIANGLE" (TPPII-related immunodeficiency,
autoimmunity, and neurodevelopmental delay with impaired glycolysis
and lysosomal expansion) syndrome are summarized in 25414442, where 4/14 presented in adulthood with white matter leasions mimicking multiple sclerosis.
Sources: Literature
DDG2P v2.55 TPP2 Dmitrijs Rots gene: TPP2 was added
gene: TPP2 was added to DDG2P. Sources: Literature
Mode of inheritance for gene: TPP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TPP2 were set to PMID: 25414442
Phenotypes for gene: TPP2 were set to Developmental delay; immunodefficiency; autoimmunity
Review for gene: TPP2 was set to GREEN
Added comment: 14 individuals with "TRIANGLE" (TPPII-related immunodeficiency,
autoimmunity, and neurodevelopmental delay with impaired glycolysis
and lysosomal expansion) syndrome are summarized in 25414442, where in 9/14 DD was present, which seems to be a common feature.
Sources: Literature
DDG2P v2.55 RASA1 Dmitrijs Rots reviewed gene: RASA1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Familial non syndromic congenital heart disease v1.65 TLL1 Dmitrijs Rots reviewed gene: TLL1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 30538173, 27418595; Phenotypes: Atrial septal defects; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v2.498 IKZF2 Boaz Palterer edited their review of gene: IKZF2: Changed publications to: 34826260, 34920454
Primary immunodeficiency or monogenic inflammatory bowel disease v2.498 IKZF2 Boaz Palterer gene: IKZF2 was added
gene: IKZF2 was added to Primary immunodeficiency. Sources: Literature
Mode of inheritance for gene: IKZF2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: IKZF2 were set to 34826260
Phenotypes for gene: IKZF2 were set to combined immunodeficiency; thrush; mucosal ulcers; chronic lymphoadenopathy; reduced MAIT cells
Penetrance for gene: IKZF2 were set to unknown
Added comment: Patients carrying the IKZF2 variant presented with a combined immunodeficiency phenotype characterized by recurrent upper respiratory infections, thrush and mucosal ulcers, and chronic lymphadenopathy. Reduced Helios expression was associated with chronic T cell activation and increased production of proinflammatory cytokines both in effector and regulatory T cells.
Sources: Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v2.498 RHBDF2 Boaz Palterer gene: RHBDF2 was added
gene: RHBDF2 was added to Primary immunodeficiency. Sources: Literature
Mode of inheritance for gene: RHBDF2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RHBDF2 were set to Pneumonia; Colitis; Immunodeficiency
Penetrance for gene: RHBDF2 were set to unknown
Review for gene: RHBDF2 was set to RED
Added comment: iRHOM deficiency with Respiratory and Intestinal inflammation and cytokine Secretion defect’ (IRIS): Kubo et al. (https://www.nature.com/articles/s41590-021-01093-y) described a new immunodeficiency disease due to loss-of-function mutations in RHBDF2, the gene encoding iRHOM2, in 4 subjects across two kindreds with recurrent infections in different organs. The disease presentation is pleiotropic, with one patient with recurrent pneumonia but no colon involvement, another had recurrent infectious hemorrhagic colitis but no lung involvement and the other two experienced recurrent respiratory infections. They replicated the phenotype in a KO mouse model and provided functional data.
Sources: Literature
Childhood onset hereditary spastic paraplegia v2.121 PI4KA Evan Reid commented on gene: PI4KA: This paper supports the idea that mutations in this gene can cause a relatively pure spastic paraplegia (PMID: 34415322 PMCID: PMC8557332 DOI: 10.1093/brain/awab124), which I think would justify inclusion of the gene on the HSP panel.
Childhood onset hereditary spastic paraplegia v2.121 PI4KA Evan Reid reviewed gene: PI4KA: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34415322; Phenotypes: spastic paraplegia, leukodystrophy, white matter abnromality, seizures, intellectual disability; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences in sex development v2.55 HHAT Eleanor Williams Phenotypes for gene: HHAT were changed from 46,XY DSD with chondrodysplasia to 46,XY DSD with chondrodysplasia; Nivelon-Nivelon-Mabille syndrome, OMIM:600092
Differences in sex development v2.54 HHAT Eleanor Williams Publications for gene: HHAT were set to 24784881
Differences in sex development v2.53 HHAT Eleanor Williams Classified gene: HHAT as Amber List (moderate evidence)
Differences in sex development v2.53 HHAT Eleanor Williams Added comment: Comment on list classification: Promoting from red to amber but with a recommendation for green rating following GMS review. 2 cases reported with 46, XY karyotype and sex reversal, plus a supportive mouse model.
Differences in sex development v2.53 HHAT Eleanor Williams Gene: hhat has been classified as Amber List (Moderate Evidence).
Differences in sex development v2.52 HHAT Eleanor Williams Tag Q4_21_rating tag was added to gene: HHAT.
Differences in sex development v2.52 HHAT Eleanor Williams reviewed gene: HHAT: Rating: GREEN; Mode of pathogenicity: None; Publications: 24784881, 30912300, 33749989; Phenotypes: Nivelon-Nivelon-Mabille syndrome, OMIM:600092; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly v2.276 HHAT Eleanor Williams Tag Q4_21_rating tag was added to gene: HHAT.
Severe microcephaly v2.276 HHAT Eleanor Williams Classified gene: HHAT as Amber List (moderate evidence)
Severe microcephaly v2.276 HHAT Eleanor Williams Added comment: Comment on list classification: Promoting from red to amber, with a recommendation for green rating following GMS review. 3 cases with microcephaly progressing to severe microcephaly reported.
Severe microcephaly v2.276 HHAT Eleanor Williams Gene: hhat has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.162 HHAT Eleanor Williams Classified gene: HHAT as Amber List (moderate evidence)
Skeletal dysplasia v2.162 HHAT Eleanor Williams Added comment: Comment on list classification: Promotion from grey to amber but with a recommendation for green rating following GMS review. 3 cases reported with a skeletal dysplasia phenotype and variants in HHAT.
Skeletal dysplasia v2.162 HHAT Eleanor Williams Gene: hhat has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.161 HHAT Eleanor Williams Tag Q4_21_rating tag was added to gene: HHAT.
Severe microcephaly v2.275 HHAT Eleanor Williams Entity copied from Skeletal dysplasia v2.161
Severe microcephaly v2.275 HHAT Eleanor Williams gene: HHAT was added
gene: HHAT was added to Severe microcephaly. Sources: Literature
Mode of inheritance for gene: HHAT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HHAT were set to 24784881; 30912300; 33749989
Phenotypes for gene: HHAT were set to Nivelon-Nivelon-Mabille syndrome, OMIM:600092
Skeletal dysplasia v2.161 HHAT Eleanor Williams changed review comment from: Associated with Nivelon-Nivelon-Mabille syndrome #600092 (AR) in OMIM.

PMID:24784881 - Callier et al 2014 - report a family with 2 siblings with Disorder of Sex Development (DSD) and chondrodysplasia (Nivelon-Nivelon-Mabille syndrome). The first sibling (46,XY karyotype) displayed severe dwarfism with generalized chondrodysplasia, a narrow, bell-shaped thorax, micromelia, brachydactyly, severe microcephaly (-7.5 SD at age 16 (PMID:15578577) with cerebellar vermis hypoplasia, facial anomalies, hypoplastic irides, and coloboma of both optic discs. Complete gonadal dysgenesis and intellectual disability is also noted. The second sibling (46,XX karyotype) had histologically normal ovaries and similar phenotypic abnormalities including severe dwarfism and generalized chondrodysplasia. Using WES a homozygous missense variant was found NM_001122834:c.860G>T:p.(Gly287Val) in HHAT in the first sibling which is in the conserved MBOAT domain. The parents were heterozygous.

PMID:30912300 - Abdel-Salam et al 2019 - report two siblings with progressive microcephaly (-6 SD at age 6 and age 3 for the 2 siblings respectively), early infantile onset seizures, and cerebellar vermis hypoplasia but notably without dwarfism and gonadal dysgenesis. Skeletal x-rays of both siblings showed nlarged epiphyses and metaphyses, thinning of the lateral 1/3 of clavicles and trapezoidal vertebral bodies. WES found a homozygous missense (c.770T>C, p.[Leu257Pro]) HHAT which is in the conserved MBOAT domain. Both parents were heterozygous for the variant.

PMID: 33749989 - Pande et al 2021 - report multiple malformations in three pregnancies with a novel biallelic in-frame deletion, c.365_367del; (p.Thr122del), in exon 5 of HHAT in the living proband. She shows severe microphthalmia, microcephaly (−8 SD head circumference at age 7), skeletal dysplasia (narrow bell-shaped tho-rax, short and angel-shaped epiphyses of hands and feet) and midfac eretrusion, short columella with a groove at the base, prominent ears, long philtrum, depressed nasal bridge, everted lower lip, and a singlec entral incisor. She also has complete sex reversal (karyotype of 46, XY, normal internal organs including uterus and ovaries.); to: Associated with Nivelon-Nivelon-Mabille syndrome #600092 (AR) in OMIM.

PMID:24784881 - Callier et al 2014 - report a family with 2 siblings with Disorder of Sex Development (DSD) and chondrodysplasia (Nivelon-Nivelon-Mabille syndrome). The first sibling (46,XY karyotype) displayed severe dwarfism with generalized chondrodysplasia, a narrow, bell-shaped thorax, micromelia, brachydactyly, severe microcephaly (-7.5 SD at age 16 (PMID:15578577) with cerebellar vermis hypoplasia, facial anomalies, hypoplastic irides, and coloboma of both optic discs. Complete gonadal dysgenesis ( including normal external female genitalia, lack of pubertal development, primary amenorrhea, and hypergonadotrophic hypogonadism) and intellectual disability is also noted. The second sibling (46,XX karyotype) had histologically normal ovaries and similar phenotypic abnormalities including severe dwarfism and generalized chondrodysplasia. Using WES a homozygous missense variant was found NM_001122834:c.860G>T:p.(Gly287Val) in HHAT in the first sibling which is in the conserved MBOAT domain. The parents were heterozygous. They also found that mice lacking functional Hhat show a similar phenotype as the syndromic 46,XY DSD patient including testicular dysgenesis and skeletal defects.

PMID:30912300 - Abdel-Salam et al 2019 - report two siblings with progressive microcephaly (-6 SD at age 6 and age 3 for the 2 siblings respectively), early infantile onset seizures, and cerebellar vermis hypoplasia but notably without dwarfism and gonadal dysgenesis. Skeletal x-rays of both siblings showed enlarged epiphyses and metaphyses, thinning of the lateral 1/3 of clavicles and trapezoidal vertebral bodies. Both sisters had a normal female karyotype (46, XX). WES found a homozygous missense (c.770T>C, p.[Leu257Pro]) HHAT which is in the conserved MBOAT domain. Both parents were heterozygous for the variant.

PMID: 33749989 - Pande et al 2021 - report multiple malformations in three pregnancies with a novel biallelic in-frame deletion, c.365_367del; (p.Thr122del), in exon 5 of HHAT in the living proband. She shows severe microphthalmia, microcephaly (−8 SD head circumference at age 7), skeletal dysplasia (narrow bell-shaped tho-rax, short and angel-shaped epiphyses of hands and feet) and midfac eretrusion, short columella with a groove at the base, prominent ears, long philtrum, depressed nasal bridge, everted lower lip, and a singlec entral incisor. She also has complete sex reversal (karyotype of 46, XY, normal internal organs including uterus and ovaries.)
Skeletal dysplasia v2.161 HHAT Eleanor Williams Phenotypes for gene: HHAT were changed from Nivelon-Nivelon-Mabille syndrome 600092 to Nivelon-Nivelon-Mabille syndrome, OMIM:600092
Skeletal dysplasia v2.160 HHAT Eleanor Williams Publications for gene: HHAT were set to 24784881; 30912300
Skeletal dysplasia v2.159 HHAT Eleanor Williams reviewed gene: HHAT: Rating: GREEN; Mode of pathogenicity: None; Publications: 24784881, 30912300, 33749989; Phenotypes: Nivelon-Nivelon-Mabille syndrome, OMIM:600092; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric or syndromic cardiomyopathy v1.59 MIB1 Ivone Leong Tag Q2_21_NHS_review was removed from gene: MIB1.
Skeletal ciliopathies v1.15 PDIA6 Eleanor Williams Classified gene: PDIA6 as Amber List (moderate evidence)
Skeletal ciliopathies v1.15 PDIA6 Eleanor Williams Added comment: Comment on list classification: Promoted from grey to amber. 1 case plus functional data.
Skeletal ciliopathies v1.15 PDIA6 Eleanor Williams Gene: pdia6 has been classified as Amber List (Moderate Evidence).
Skeletal ciliopathies v1.14 PDIA6 Eleanor Williams changed review comment from: Not associated with a phenotype in OMIM. In Gene2Phenotype it is associated with PDIA6-associated syndromic neonatal diabetes and asphyxiating thoracic dystrophy with Limited confidence.

As Zornitza Stark reports PMID: 33495992 (Al-Fadhli et al 2021) describes one case of a child with asphyxiating thoracic dystrophy (ATD) syndrome and infantile-onset diabetes who had a homozygous frameshift variant in the PDIA6 gene (NM_001282704.1:c.703del (p.Val235fs)) which is in exon 8 (of 15). The parents and unaffected sibling were heterozygous for this variant. The authors state that PDIA6 is not known yet to be involved in the formation or function of the primary cilia but suggest that it could be directly or indirectly interacting or required for proper protein folding of known or unknown ciliopathy protein. The X-ray findings at 6 months were consistent with typical radiological features of ATD syndrome.; to: Not associated with a phenotype in OMIM. In Gene2Phenotype it is associated with PDIA6-associated syndromic neonatal diabetes and asphyxiating thoracic dystrophy with Limited confidence.

As Zornitza Stark reports PMID: 33495992 (Al-Fadhli et al 2021) describes one case of a child with asphyxiating thoracic dystrophy (ATD) syndrome and infantile-onset diabetes who had a homozygous frameshift variant in the PDIA6 gene (NM_001282704.1:c.703del (p.Val235fs)) which is in exon 8 (of 15). The parents and unaffected sibling were heterozygous for this variant. The authors state that PDIA6 is not known yet to be involved in the formation or function of the primary cilia but suggest that it could be directly or indirectly interacting or required for proper protein folding of known or unknown ciliopathy protein.

The X-ray findings at 6 months were consistent with typical radiological features of ATD syndrome. Other features include intrauterine growth retardation, multiple cysts in both kidneys associated with renal oligohydramnios (in first antenatal ultrasound) and hyperglycemia on the second day of life.
Skeletal ciliopathies v1.14 PDIA6 Eleanor Williams commented on gene: PDIA6
Skeletal ciliopathies v1.14 CSPP1 Eleanor Williams Classified gene: CSPP1 as Amber List (moderate evidence)
Skeletal ciliopathies v1.14 CSPP1 Eleanor Williams Added comment: Comment on list classification: Promoting from grey to amber, but with a recommendation for green rating following GMS review. 3 cases reported with a skeletal phenotype.
Skeletal ciliopathies v1.14 CSPP1 Eleanor Williams Gene: cspp1 has been classified as Amber List (Moderate Evidence).
Skeletal ciliopathies v1.13 CSPP1 Eleanor Williams Tag Q4_21_rating tag was added to gene: CSPP1.
Skeletal ciliopathies v1.13 CSPP1 Eleanor Williams Phenotypes for gene: CSPP1 were changed from Joubert syndrome 21, MIM# 615636 to Joubert syndrome 21, OMIM:615636; Joubert syndrome with Jeune asphyxiating thoracic dystrophy, MONDO:0018342
Skeletal ciliopathies v1.12 CSPP1 Eleanor Williams Publications for gene: CSPP1 were set to 24360808
Skeletal ciliopathies v1.11 CSPP1 Eleanor Williams reviewed gene: CSPP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24360808, 24360803; Phenotypes: Joubert syndrome 21, OMIM:615636, Joubert syndrome with Jeune asphyxiating thoracic dystrophy, MONDO:0018342; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary ataxia with onset in adulthood v2.137 HEXB Arina Puzriakova Phenotypes for gene: HEXB were changed from Sandhoff disease, infantile, juvenile, and adult forms, 268800; Sandhoff disease, 268800 to Sandhoff disease, infantile, juvenile, and adult forms, OMIM:268800
Early onset or syndromic epilepsy v2.483 HEXB Arina Puzriakova Phenotypes for gene: HEXB were changed from Sandhoff disease, infantile, juvenile, and adult forms, 268800; seizures; myoclonic epilepsy to Sandhoff disease, infantile, juvenile, and adult forms, OMIM:268800
Familial pulmonary fibrosis v1.18 ACD Øystein Holla gene: ACD was added
gene: ACD was added to Familial pulmonary fibrosis. Sources: Literature
Mode of inheritance for gene: ACD was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: ACD were set to 31515401
Phenotypes for gene: ACD were set to dyskeratosis congenita, telomere disorder, pulmonary fibrosis
Penetrance for gene: ACD were set to unknown
Review for gene: ACD was set to GREEN
gene: ACD was marked as current diagnostic
Added comment: Pathogenic variants in ACD cause dyskeratosis congenita (DC) and short telomeres.
People with DC are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML), solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis.
(GeneReviews Dyskeratosis Congenita, Last Revision: November 21, 2019.)

Unaffected heterozygotes are reported, PMID: 33446513
Sources: Literature
Malformations of cortical development v2.129 RAB3GAP2 Sarah Leigh Phenotypes for gene: RAB3GAP2 were changed from Warburg micro syndrome 2, OMIM:614225 to Warburg micro syndrome 2, OMIM:614225; Warburg micro syndrome 2 MONDO:0013641
Malformations of cortical development v2.128 RAB3GAP2 Sarah Leigh Publications for gene: RAB3GAP2 were set to 23420520; 20967465
Malformations of cortical development v2.127 RAB3GAP2 Sarah Leigh Tag Q4_21_rating tag was added to gene: RAB3GAP2.
Malformations of cortical development v2.127 RAB3GAP2 Sarah Leigh edited their review of gene: RAB3GAP2: Added comment: Associated with relevant phenotype in OMIM, but not associated with Warburg micro syndrome 2 OMIM:614225 in Gen2Phen. At least four variants reported in at least four unrelated cases..; Changed rating: GREEN
Severe microcephaly v2.274 TP53RK Eleanor Williams edited their review of gene: TP53RK: Changed rating: GREEN
Malformations of cortical development v2.127 RAB3GAP2 Sarah Leigh Classified gene: RAB3GAP2 as Amber List (moderate evidence)
Malformations of cortical development v2.127 RAB3GAP2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Malformations of cortical development v2.127 RAB3GAP2 Sarah Leigh Gene: rab3gap2 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.126 RAB3GAP1 Sarah Leigh Publications for gene: RAB3GAP1 were set to 23420520; 32740904
Malformations of cortical development v2.125 RAB3GAP1 Sarah Leigh edited their review of gene: RAB3GAP1: Added comment: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. At least 13 variants reported in at least 12 unrelated cases; Changed rating: GREEN
Malformations of cortical development v2.125 RAB3GAP1 Sarah Leigh Phenotypes for gene: RAB3GAP1 were changed from Warburg micro syndrome 1, OMIM:600118 to Warburg micro syndrome 1 OMIM:600118; Warburg micro syndrome 1 MONDO:0010822
Rare syndromic craniosynostosis or isolated multisuture synostosis v2.60 B3GAT3 Eleanor Williams Tag Q3_21_NHS_review tag was added to gene: B3GAT3.
Malformations of cortical development v2.124 RAB3GAP1 Sarah Leigh Tag Q4_21_rating tag was added to gene: RAB3GAP1.
Malformations of cortical development v2.124 RAB3GAP1 Sarah Leigh Classified gene: RAB3GAP1 as Amber List (moderate evidence)
Malformations of cortical development v2.124 RAB3GAP1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Malformations of cortical development v2.124 RAB3GAP1 Sarah Leigh Gene: rab3gap1 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.123 DAG1 Sarah Leigh Classified gene: DAG1 as Green List (high evidence)
Malformations of cortical development v2.123 DAG1 Sarah Leigh Added comment: Comment on list classification: There is not enough evidence for this gene to be rated GREEN at the next major review.
Malformations of cortical development v2.123 DAG1 Sarah Leigh Gene: dag1 has been classified as Green List (High Evidence).
Malformations of cortical development v2.122 DAG1 Sarah Leigh reviewed gene: DAG1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Skeletal dysplasia v2.159 MESD Eleanor Williams Tag Q3_21_NHS_review tag was added to gene: MESD.
Malformations of cortical development v2.122 DAG1 Sarah Leigh Tag Q4_21_expert_review tag was added to gene: DAG1.
Malformations of cortical development v2.122 DAG1 Sarah Leigh Publications for gene: DAG1 were set to 24052401; 25934851
Malformations of cortical development v2.121 DAG1 Sarah Leigh Publications for gene: DAG1 were set to 24052401
Malformations of cortical development v2.120 PTEN Sarah Leigh edited their review of gene: PTEN: Added comment: In the retrospective study PMID: 32162846, the authors observe four unrelated cases who exhibit polymicrogyria.; Changed rating: GREEN
Malformations of cortical development v2.120 PTEN Sarah Leigh Tag Q4_21_rating tag was added to gene: PTEN.
Malformations of cortical development v2.120 PTEN Sarah Leigh Classified gene: PTEN as Amber List (moderate evidence)
Malformations of cortical development v2.120 PTEN Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Malformations of cortical development v2.120 PTEN Sarah Leigh Gene: pten has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.119 PTEN Sarah Leigh Phenotypes for gene: PTEN were changed from Cowden syndrome 1 158350; Lhermitte-Duclos syndrome 158350; Macrocephaly/autism syndrome 605309 to Cowden syndrome 1 OMIM:158350; Lhermitte-Duclos syndrome OMIM:158350; Cowden syndrome 1 MONDO:0008021; Macrocephaly/autism syndrome OMIM:605309; macrocephaly-autism syndrome MONDO:0011537
Adult onset leukodystrophy v1.36 CTC1 Ivone Leong Tag Q3_21_expert_review tag was added to gene: CTC1.
Hereditary ataxia with onset in adulthood v2.136 B4GAT1 Ivone Leong Tag Q3_21_rating tag was added to gene: B4GAT1.
Adult onset hereditary spastic paraplegia v1.88 SERAC1 Ivone Leong Tag Q3_21_phenotype tag was added to gene: SERAC1.
Rare syndromic craniosynostosis or isolated multisuture synostosis v2.60 HNRNPK Ivone Leong Tag Q3_21_rating tag was added to gene: HNRNPK.
White matter disorders and cerebral calcification - narrow panel v1.220 PTEN Ivone Leong Tag Q3_21_rating tag was added to gene: PTEN.
White matter disorders and cerebral calcification - narrow panel v1.220 ERCC1 Ivone Leong Tag Q3_21_rating tag was added to gene: ERCC1.
Skeletal dysplasia v2.159 PRKG2 Eleanor Williams Tag Q4_21_NHS_review tag was added to gene: PRKG2.
Ataxia and cerebellar anomalies - narrow panel v2.279 ALDH5A1 Ivone Leong Tag Q3_21_rating tag was added to gene: ALDH5A1.
Hypogonadotropic hypogonadism v1.33 SPRY4 Ivone Leong Tag Q2_21_expert_review was removed from gene: SPRY4.
Hypogonadotropic hypogonadism (GMS) v1.48 SPRY4 Ivone Leong Entity copied from Hypogonadotropic hypogonadism v1.33
Hypogonadotropic hypogonadism (GMS) v1.48 SPRY4 Ivone Leong gene: SPRY4 was added
gene: SPRY4 was added to Hypogonadotropic hypogonadism idiopathic. Sources: Expert Review Amber,Radboud University Medical Center, Nijmegen,Expert list,Literature
monogenic-polygenic, Q2_21_expert_review tags were added to gene: SPRY4.
Mode of inheritance for gene: SPRY4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SPRY4 were set to 23643382; 32389901
Phenotypes for gene: SPRY4 were set to Hypogonadotropic hypogonadism 17 with or without anosmia, OMIM:615266
Penetrance for gene: SPRY4 were set to Complete
Congenital disorders of glycosylation v2.78 TMEM199 Ivone Leong Tag Q3_21_rating tag was added to gene: TMEM199.
Hereditary neuropathy or pain disorder v1.78 MME Arina Puzriakova Tag Q4_21_expert_review tag was added to gene: MME.
Hereditary neuropathy or pain disorder v1.78 MME Arina Puzriakova Added comment: Comment on mode of inheritance: Heterozygous variants have been identified in >10 individuals with late-onset CMT2T. However, some variants have been found in control databases and family studies indicate incomplete penetrance, suggesting heterozygous variants only confer susceptibility. Nonetheless, sufficient cases have been reported in literature and both MOIs are listed in OMIM for this phenotype, and so inclusion of monoallelic inheritance on this panel will first be flagged for GMS review.
Hereditary neuropathy or pain disorder v1.78 MME Arina Puzriakova Mode of inheritance for gene: MME was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v1.77 MME Arina Puzriakova Tag adult-onset tag was added to gene: MME.
Tag Q4_21_MOI tag was added to gene: MME.
Adult onset leukodystrophy v1.36 AARS Ivone Leong Tag Q2_21_rating was removed from gene: AARS.
Tag Q4_21_expert_review tag was added to gene: AARS.
Adult onset leukodystrophy v1.36 AARS Ivone Leong Tag Q2_21_rating tag was added to gene: AARS.
Hereditary neuropathy v1.432 MME Arina Puzriakova Publications for gene: MME were set to 26991897; 27588448
Hereditary neuropathy or pain disorder v1.77 MME Arina Puzriakova Publications for gene: MME were set to 26991897; 27588448
Hereditary neuropathy v1.431 MME Arina Puzriakova Phenotypes for gene: MME were changed from Charcot-Marie-Tooth disease, axonal, type 2T, 617017 to Charcot-Marie-Tooth disease, axonal, type 2T, OMIM:617017
Hereditary neuropathy or pain disorder v1.76 MME Arina Puzriakova Phenotypes for gene: MME were changed from Charcot-Marie-Tooth disease, axonal, type 2T, 617017 to Charcot-Marie-Tooth disease, axonal, type 2T, OMIM:617017
Likely inborn error of metabolism v2.208 TARS2 Sarah Leigh Classified gene: TARS2 as Amber List (moderate evidence)
Likely inborn error of metabolism v2.208 TARS2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Likely inborn error of metabolism v2.208 TARS2 Sarah Leigh Gene: tars2 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v2.207 TARS2 Sarah Leigh Tag Q4_21_rating tag was added to gene: TARS2.
Hereditary ataxia with onset in adulthood v2.136 MME Arina Puzriakova Publications for gene: MME were set to
Hereditary ataxia with onset in adulthood v2.135 MME Arina Puzriakova Phenotypes for gene: MME were changed from Spinocerebellar ataxia type 43, 617018 to ?Spinocerebellar ataxia 43, OMIM:617018
Childhood onset dystonia, chorea or related movement disorder v1.209 TARS2 Sarah Leigh Tag Q4_21_rating tag was added to gene: TARS2.
Childhood onset dystonia, chorea or related movement disorder v1.209 TARS2 Sarah Leigh Classified gene: TARS2 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v1.209 TARS2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Childhood onset dystonia, chorea or related movement disorder v1.209 TARS2 Sarah Leigh Gene: tars2 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.208 TARS2 Sarah Leigh Classified gene: TARS2 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v1.208 TARS2 Sarah Leigh Gene: tars2 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.207 TARS2 Sarah Leigh changed review comment from: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 11 variants reported in at least 7 unrelated cases with a varied phenotype, including encephalomyopathy, epilepsy, dystonia, hyperhidrosis and severe hearing impairment. Supportive functional studies were also presented PMID: 34508595.; to: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 11 variants reported in at least 7 unrelated cases with a varied phenotype, including encephalomyopathy, epilepsy, dystonia, hyperhidrosis and severe hearing impairment. At least three unrelated cases of dystonia reported. Supportive functional studies were also presented PMID: 34508595.
Childhood onset dystonia, chorea or related movement disorder v1.207 TARS2 Sarah Leigh Publications for gene: TARS2 were set to
Hereditary neuropathy or pain disorder v1.75 MME Arina Puzriakova Tag Q4_21_NHS_review tag was added to gene: MME.
Childhood onset dystonia, chorea or related movement disorder v1.206 TARS2 Sarah Leigh Mode of inheritance for gene: TARS2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Possible mitochondrial disorder - nuclear genes v1.62 TARS2 Sarah Leigh Phenotypes for gene: TARS2 were changed from ?Combined oxidative phosphorylation deficiency 21, 615918 to Combined oxidative phosphorylation deficiency 21 OMIM:615918; combined oxidative phosphorylation defect type 21 MONDO:0014398
Likely inborn error of metabolism v2.207 TARS2 Sarah Leigh Phenotypes for gene: TARS2 were changed from Multiple respiratory chain complex deficiencies (disorders of protein synthesis); ?Combined oxidative phosphorylation deficiency 21, 615918 to Combined oxidative phosphorylation deficiency 21 OMIM:615918; combined oxidative phosphorylation defect type 21 MONDO:0014398
Possible mitochondrial disorder - nuclear genes v1.61 TARS2 Sarah Leigh Publications for gene: TARS2 were set to
Likely inborn error of metabolism v2.206 TARS2 Sarah Leigh Added comment: Comment on publications: PMID: 24827421 - Compound heterozygous variants in TARS2 were reported in the proband and his affected sister - a missense mutation (c.845C>T, p.Pro282Leu) and a nucleotide change in position +3 of intron 6 (g.4255A>G, c.695+3A>G). The parents carrying one of the variants, one unaffected sister carried one variant, and the other unaffected sibling carried neither.
Likely inborn error of metabolism v2.206 TARS2 Sarah Leigh Publications for gene: TARS2 were set to PMID: 24827421 - Compound heterozygous variants in TARS2 were reported in the proband and his affected sister - a missense mutation (c.845C>T, p.Pro282Leu) and a nucleotide change in position +3 of intron 6 (g.4255A>G, c.695+3A>G). The parents carrying one of the variants, one unaffected sister carried one variant, and the other unaffected sibling carried neither.
Likely inborn error of metabolism v2.205 TARS2 Sarah Leigh reviewed gene: TARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33153448, 24827421, 34508595; Phenotypes: Combined oxidative phosphorylation deficiency 21 OMIM:615918, combined oxidative phosphorylation defect type 21 MONDO:0014398; Mode of inheritance: None
Possible mitochondrial disorder - nuclear genes v1.60 TARS2 Sarah Leigh reviewed gene: TARS2: Rating: AMBER; Mode of pathogenicity: None; Publications: 33153448, 24827421, 34508595; Phenotypes: Combined oxidative phosphorylation deficiency 21 OMIM:615918, combined oxidative phosphorylation defect type 21 MONDO:0014398; Mode of inheritance: None
Childhood onset dystonia, chorea or related movement disorder v1.205 TARS2 Sarah Leigh reviewed gene: TARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33153448, 24827421, 34508595; Phenotypes: Combined oxidative phosphorylation deficiency 21 OMIM:615918, combined oxidative phosphorylation defect type 21 MONDO:0014398; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v2.73 TARS2 Sarah Leigh Phenotypes for gene: TARS2 were changed from Combined oxidative phosphorylation deficiency 21 OMIM:615918; combined oxidative phosphorylation defect type 21MONDO:0014398 to Combined oxidative phosphorylation deficiency 21 OMIM:615918; combined oxidative phosphorylation defect type 21 MONDO:0014398
Mitochondrial disorders v2.72 TARS2 Sarah Leigh Phenotypes for gene: TARS2 were changed from Combined oxidative phosphorylation deficiency 21 OMIM:615918; combined oxidative phosphorylation defect type 21MONDO:0014398 to Combined oxidative phosphorylation deficiency 21 OMIM:615918; combined oxidative phosphorylation defect type 21MONDO:0014398
Mitochondrial disorders v2.72 TARS2 Sarah Leigh Phenotypes for gene: TARS2 were changed from Combined oxidative phosphorylation deficiency 21 OMIM:615918 to Combined oxidative phosphorylation deficiency 21 OMIM:615918; combined oxidative phosphorylation defect type 21MONDO:0014398
Amyotrophic lateral sclerosis/motor neuron disease v1.49 KIF5A Andrey Gagunashvili gene: KIF5A was added
gene: KIF5A was added to Amyotrophic lateral sclerosis/motor neuron disease. Sources: Literature
Mode of inheritance for gene: KIF5A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KIF5A were set to 29566793; 29342275; 30581417; 33077544; 34873335
Phenotypes for gene: KIF5A were set to Amyotrophic lateral sclerosis
Penetrance for gene: KIF5A were set to unknown
Review for gene: KIF5A was set to GREEN
Added comment: "...mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases." (Nicolas et al., 2018)
Sources: Literature
Renal ciliopathies v1.45 IFT140 Eleanor Williams Added comment: Comment on mode of inheritance: Leaving the mode of inheritance as biallelic for now, but with a recommendation that it should be updated to BOTH monoallelic and biallelic following GMS review.
Renal ciliopathies v1.45 IFT140 Eleanor Williams Mode of inheritance for gene: IFT140 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Renal ciliopathies v1.44 IFT140 Eleanor Williams Phenotypes for gene: IFT140 were changed from Short-rib thoracic dysplasia 9 with or without polydactyly, OMIM #266920 (aka Mainzer-Saldino syndrome) to Short-rib thoracic dysplasia 9 with or without polydactyly, OMIM:266920; short-rib thoracic dysplasia 9 with or without polydactyly, MONDO:0009964; cystic kidney disease, MONDO:0002473
Renal ciliopathies v1.43 IFT140 Eleanor Williams Publications for gene: IFT140 were set to PMID: 22503633, 23418020, 29706353
Renal ciliopathies v1.42 IFT140 Eleanor Williams Tag Q4_21_MOI tag was added to gene: IFT140.
Tag Q4_21_NHS_review tag was added to gene: IFT140.
Renal ciliopathies v1.42 IFT140 Eleanor Williams reviewed gene: IFT140: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mitochondrial disorders v2.71 TARS2 Sarah Leigh edited their review of gene: TARS2: Added comment: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 11 variants reported in at least 7 unrelated cases with a varied phenotype, including encephalomyopathy, epilepsy, dystonia, hyperhidrosis and severe hearing impairment.; Changed rating: GREEN
Mitochondrial disorders v2.71 TARS2 Sarah Leigh Tag Q4_21_rating tag was added to gene: TARS2.
Mitochondrial disorders v2.71 TARS2 Sarah Leigh Classified gene: TARS2 as Amber List (moderate evidence)
Mitochondrial disorders v2.71 TARS2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Mitochondrial disorders v2.71 TARS2 Sarah Leigh Gene: tars2 has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v2.70 TARS2 Sarah Leigh Phenotypes for gene: TARS2 were changed from Multiple respiratory chain complex deficiencies (disorders of protein synthesis); ?Combined oxidative phosphorylation deficiency 21, 615918 to Combined oxidative phosphorylation deficiency 21 OMIM:615918
Mitochondrial disorders v2.69 TARS2 Sarah Leigh Added comment: Comment on publications: PMID: 24827421 - Compound heterozygous variants in TARS2 were reported in the proband and his affected sister - a missense mutation (c.845C>T, p.Pro282Leu) and a nucleotide change in position +3 of intron 6 (g.4255A>G, c.695+3A>G). The parents carrying one of the variants, one unaffected sister carried one variant, and the other unaffected sibling carried neither.
Mitochondrial disorders v2.69 TARS2 Sarah Leigh Publications for gene: TARS2 were set to PMID: 24827421 - Compound heterozygous variants in TARS2 were reported in the proband and his affected sister - a missense mutation (c.845C>T, p.Pro282Leu) and a nucleotide change in position +3 of intron 6 (g.4255A>G, c.695+3A>G). The parents carrying one of the variants, one unaffected sister carried one variant, and the other unaffected sibling carried neither.
Arthrogryposis v3.145 SLC6A9 Arina Puzriakova Tag Q4_21_NHS_review tag was added to gene: SLC6A9.
Skeletal dysplasia v2.159 ZNF687 Arina Puzriakova Tag Q4_21_NHS_review tag was added to gene: ZNF687.
Hypertrophic cardiomyopathy v2.32 GYG1 Arina Puzriakova Tag Q4_21_NHS_review tag was added to gene: GYG1.
Proteinuric renal disease v2.61 LCAT Arina Puzriakova Tag Q4_21_NHS_review tag was added to gene: LCAT.
Hereditary neuropathy or pain disorder v1.75 C1orf194 Arina Puzriakova Tag Q3_21_rating tag was added to gene: C1orf194.
Unexplained young onset end-stage renal disease v1.23 TRIM8 Arina Puzriakova Tag Q4_21_NHS_review tag was added to gene: TRIM8.
Ichthyosis and erythrokeratoderma v1.69 ALDH3A2 Arina Puzriakova Tag Q3_21_NHS_review tag was added to gene: ALDH3A2.
Childhood onset hereditary spastic paraplegia v2.121 HPDL Arina Puzriakova Tag Q2_21_NHS_review tag was added to gene: HPDL.
Childhood onset dystonia, chorea or related movement disorder v1.205 C9orf72 Arina Puzriakova Tag Q4_21_NHS_review tag was added to gene: C9orf72.
Early onset or syndromic epilepsy v2.482 UFSP2 Arina Puzriakova Tag Q2_21_NHS_review tag was added to gene: UFSP2.
Hereditary ataxia with onset in adulthood v2.134 VPS41 Arina Puzriakova Tag Q2_21_NHS_review tag was added to gene: VPS41.
Adult onset dystonia, chorea or related movement disorder v1.161 VPS41 Arina Puzriakova Tag Q2_21_NHS_review tag was added to gene: VPS41.
Ataxia and cerebellar anomalies - narrow panel v2.279 VPS41 Arina Puzriakova Tag Q2_21_NHS_review tag was added to gene: VPS41.
Cystic kidney disease v2.27 FLCN Arina Puzriakova Tag Q2_21_NHS_review tag was added to gene: FLCN.
Intellectual disability v3.1484 HEXB Arina Puzriakova Phenotypes for gene: HEXB were changed from Sandhoff disease, infantile, juvenile, and adult forms, 268800; GM2-GANGLIOSIDOSIS TYPE 2 (GM2G2) to Sandhoff disease, infantile, juvenile, and adult forms, OMIM:268800
Likely inborn error of metabolism v2.205 HEXB Arina Puzriakova Phenotypes for gene: HEXB were changed from Sandhoff disease, infantile, juvenile, and adult forms, 268800 to Sandhoff disease, infantile, juvenile, and adult forms, OMIM:268800
Fetal anomalies v1.821 HEXB Arina Puzriakova Phenotypes for gene: HEXB were changed from GM2-GANGLIOSIDOSIS TYPE 2 to Sandhoff disease, infantile, juvenile, and adult forms, OMIM:268800
Undiagnosed metabolic disorders v1.503 HEXB Arina Puzriakova Phenotypes for gene: HEXB were changed from Sandhoff disease, infantile, juvenile, and adult forms 268800 to Sandhoff disease, infantile, juvenile, and adult forms, OMIM:268800
Adult onset neurodegenerative disorder v2.258 HEXB Arina Puzriakova Phenotypes for gene: HEXB were changed from Sandhoff disease, infantile, juvenile, and adult forms, 268800 to Sandhoff disease, infantile, juvenile, and adult forms, OMIM:268800
Hereditary ataxia v1.281 HEXB Arina Puzriakova Phenotypes for gene: HEXB were changed from Sandhoff disease, infantile, juvenile, and adult forms, 268800 to Sandhoff disease, infantile, juvenile, and adult forms, OMIM:268800
Ataxia and cerebellar anomalies - narrow panel v2.279 HEXB Arina Puzriakova Phenotypes for gene: HEXB were changed from Sandhoff disease, infantile, juvenile, and adult forms, 268800 to Sandhoff disease, infantile, juvenile, and adult forms, OMIM:268800
Hereditary neuropathy or pain disorder v1.75 HEXB Arina Puzriakova Tag Q4_21_rating tag was added to gene: HEXB.
Hereditary neuropathy or pain disorder v1.75 HEXB Arina Puzriakova Publications for gene: HEXB were set to 17015493; 20472204; 20798201; 2795083; 31512525; 34856081
Hereditary neuropathy or pain disorder v1.74 HEXB Arina Puzriakova Publications for gene: HEXB were set to PMID: 31512525
Hereditary neuropathy or pain disorder v1.73 HEXB Arina Puzriakova Classified gene: HEXB as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v1.73 HEXB Arina Puzriakova Added comment: Comment on list classification: Neuropathy has been described in Sandhoff disease, particularly in adult-onset cases where this can be an initial finding and other symptoms may be more mild. Sufficient unrelated cases of neuropathy due to variants in this gene have been reported in literature (>3). Overall HEXB should be promoted to Green at the next GMS panel update.
Hereditary neuropathy or pain disorder v1.73 HEXB Arina Puzriakova Gene: hexb has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v1.72 HEXB Arina Puzriakova Phenotypes for gene: HEXB were changed from to Sandhoff disease, infantile, juvenile, and adult forms, OMIM:268800
Hereditary neuropathy or pain disorder v1.71 HEXA Arina Puzriakova Publications for gene: HEXA were set to PMID: 28739864; 18642377
Hereditary neuropathy or pain disorder v1.70 HEXA Arina Puzriakova Tag Q4_21_rating tag was added to gene: HEXA.
Hereditary neuropathy or pain disorder v1.70 HEXA Arina Puzriakova Classified gene: HEXA as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v1.70 HEXA Arina Puzriakova Added comment: Comment on list classification: Neuronopathy and peripheral neuropathy have been described in Tay-Sachs disease, particularly in adult-onset cases where this can be an initial finding and other symptoms may be more mild. Sufficient unrelated cases of neuropathy due to variants in this gene have been reported in literature (>3). Overall HEXA should be promoted to Green at the next GMS panel update.
Hereditary neuropathy or pain disorder v1.70 HEXA Arina Puzriakova Gene: hexa has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v1.69 HEXA Arina Puzriakova Phenotypes for gene: HEXA were changed from to Tay-Sachs disease, OMIM:272800; Late-onset Tay-Sachs disease
Intellectual disability v3.1483 ATAD1 Ivone Leong Phenotypes for gene: ATAD1 were changed from Hyperekplexia 4, MIM#618011 to Hyperekplexia 4, OMIM:618011
Intellectual disability v3.1482 ATAD1 Ivone Leong Publications for gene: ATAD1 were set to 28180185
Malformations of cortical development v2.118 RAB3GAP1 Ivone Leong Added comment: Comment on publications: More cases PMID: 32740904
Malformations of cortical development v2.118 RAB3GAP1 Ivone Leong Publications for gene: RAB3GAP1 were set to 23420520
Malformations of cortical development v2.117 RAB3GAP1 Ivone Leong Phenotypes for gene: RAB3GAP1 were changed from Warburg micro syndrome 1, MIM# 600118 to Warburg micro syndrome 1, OMIM:600118
Malformations of cortical development v2.116 RAB18 Ivone Leong Tag Q4_21_rating tag was added to gene: RAB18.
Malformations of cortical development v2.116 RAB18 Ivone Leong Classified gene: RAB18 as Amber List (moderate evidence)
Malformations of cortical development v2.116 RAB18 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype (Definitive). There is enough evidence to support a gene-disease association. This gene should be Green at the next review.
Malformations of cortical development v2.116 RAB18 Ivone Leong Gene: rab18 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.820 KIDINS220 Arina Puzriakova Tag Q2_21_expert_review tag was added to gene: KIDINS220.
Malformations of cortical development v2.115 RAB18 Ivone Leong Phenotypes for gene: RAB18 were changed from Warburg micro syndrome 3, MIM# 614222 to Warburg micro syndrome 3, OMIM:614222
Malformations of cortical development v2.114 NPRL3 Ivone Leong Tag Q4_21_rating tag was added to gene: NPRL3.
Malformations of cortical development v2.114 NPRL3 Ivone Leong Classified gene: NPRL3 as Amber List (moderate evidence)
Malformations of cortical development v2.114 NPRL3 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in OMIM but not Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be given a Green rating at the next review.
Malformations of cortical development v2.114 NPRL3 Ivone Leong Gene: nprl3 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.113 NPRL3 Ivone Leong Phenotypes for gene: NPRL3 were changed from Epilepsy, familial focal, with variable foci 3 (MIM#617118) to Epilepsy, familial focal, with variable foci 3, OMIM:617118
Intellectual disability v3.1481 KCND2 Eleanor Williams Classified gene: KCND2 as Amber List (moderate evidence)
Intellectual disability v3.1481 KCND2 Eleanor Williams Added comment: Comment on list classification: Promoting from red to amber but with a recommendation for green rating following GMS review. 3 cases reported with missense variants in this gene with no seizures, plus further cases with seizures.
Intellectual disability v3.1481 KCND2 Eleanor Williams Gene: kcnd2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v3.1480 KCND2 Eleanor Williams Tag Q4_21_rating tag was added to gene: KCND2.
Intellectual disability v3.1480 KCND2 Eleanor Williams gene: KCND2 was added
gene: KCND2 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: KCND2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KCND2 were set to 34245260; 16934482; 24501278
Phenotypes for gene: KCND2 were set to global developmental delay, HP:0001263
Mode of pathogenicity for gene: KCND2 was set to Other
Added comment: 6 new unrelated cases with developmental delay reported in PMID: 34245260 (Zhang et al 2021), 3 of whom had seizures. All had heterozygous missense variants of KCND2 in sites known to be critical for channel gating (E323K, P403A, two individuals, V404L, two individuals and V404M). Functional studies suggest that these missense changes cause both a partial loss-of-function (LOF) and gain-of-function (GOF). The V404 change appears to increase epileptic seizure susceptibility with the 3 patients with a V404 change showing this phenotype.

PMID:16934482 - Singh et al, 2006 - reports a patient with cognitive impairment who also went on to have seizures starting from age 13 with a 5 bp deletion in KCND2 leading to premature stop codon. The proband's asymptomatic father also shared this variant.

Also:
PMID:24501278 - Lee et al, 2014 - reports pair of monozygotic twin boys with infantile onset severe refractory epilepsy and autism. A de novo heterozygous missense variant was identified by WES - V404M.
Sources: Literature
Early onset or syndromic epilepsy v2.482 KCND2 Eleanor Williams changed review comment from: 6 new unrelated cases with developmental delay reported in PMID: 34245260 (Zhang et al 2021), 3 of whom had seizures. All had heterozygous missense variants of KCND2 in sites known to be critical for channel gating (E323K, P403A, two individuals, V404L, two individuals and V404M). Functional studies suggest that these missense changes cause both a partial loss-of-function (LOF) and gain-of-function (GOF). The V404 change appears to increase epileptic seizure susceptibility with the 3 patients with a V404 change showing this phenotype.; to: 6 new unrelated cases with developmental delay reported in PMID: 34245260 (Zhang et al 2021), 3 of whom had seizures. All had heterozygous missense variants of KCND2 in sites known to be critical for channel gating (E323K, P403A, two individuals, V404L, two individuals and V404M). Functional studies suggest that these missense changes cause both a partial loss-of-function (LOF) and gain-of-function (GOF). The V404 change appears to increase epileptic seizure susceptibility with the 3 patients with a V404 change showing this phenotype.

PMID:24501278 - Lee et al, 2014 - reports pair of monozygotic twin boys with infantile onset severe refractory epilepsy and autism. A de novo heterozygous missense variant was identified by WES - V404M.

PMID: 29581270 - Lin et al, 2018 - performed functional work that shows V404M enhances inactivation of channels that have not yet opened and dramatically impairs the inactivation of channels that have opened.

PMID:16934482 - Singh et al, 2006 - reports a patient with cognative impairment who also went on to have seizures starting from age 13 with a 5 bp deletion in KCND2 leading to premature stop codon. The proband's asymptomatic father also shared this variant.
Early onset or syndromic epilepsy v2.482 KCND2 Eleanor Williams Classified gene: KCND2 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v2.482 KCND2 Eleanor Williams Added comment: Comment on list classification: Promoting from red to amber with a recommendation for green rating following GMS review. 4 unrelated cases with a V404 missense variant and epilepsy.
Early onset or syndromic epilepsy v2.482 KCND2 Eleanor Williams Gene: kcnd2 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v2.481 KCND2 Eleanor Williams Phenotypes for gene: KCND2 were changed from epilepsy; seizures to epilepsy, NBO:0000642; seizure, HP:0001250
Early onset or syndromic epilepsy v2.480 KCND2 Eleanor Williams Phenotypes for gene: KCND2 were changed from epilepsy; autism to epilepsy; seizures
Early onset or syndromic epilepsy v2.479 KCND2 Eleanor Williams Publications for gene: KCND2 were set to 24501278; 16934482; 29581270
Early onset or syndromic epilepsy v2.478 KCND2 Eleanor Williams Tag Q4_21_rating tag was added to gene: KCND2.
Early onset or syndromic epilepsy v2.478 KCND2 Eleanor Williams reviewed gene: KCND2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34245260; Phenotypes: seizures; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Renal ciliopathies v1.42 IFT140 John Sayer reviewed gene: IFT140: Rating: GREEN; Mode of pathogenicity: None; Publications: https://doi.org/10.1016/j.ajhg.2021.11.016; Phenotypes: Cystic kidney disease, cystic liver disease; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Hereditary Erythrocytosis v1.42 SH2B3 Arina Puzriakova changed review comment from: Eligibility criteria for this panel states that secondary causes of erythrocytosis such as myeloproliferative neoplasm must be excluded prior to testing.; to: Eligibility criteria for this panel (R405) states that secondary causes of erythrocytosis such as myeloproliferative neoplasm must be excluded prior to testing.
Hereditary Erythrocytosis v1.42 SH2B3 Arina Puzriakova commented on gene: SH2B3
Hereditary Erythrocytosis v1.42 SLC30A10 Arina Puzriakova Publications for gene: SLC30A10 were set to PMID: 22341971; 22341972
Hereditary Erythrocytosis v1.41 SLC30A10 Arina Puzriakova Classified gene: SLC30A10 as Amber List (moderate evidence)
Hereditary Erythrocytosis v1.41 SLC30A10 Arina Puzriakova Added comment: Comment on list classification: New gene added to this panel by external reviewer Dmitrijs Rots. There is enough evidence to promote this gene to Green at the next GMS panel update. All affected individuals reported to date (>3) had polycythemia at the time of diagnosis, which can precede the onset of neurologic manifestations and therefore it is worth including SLC30A10 on this panel.
Hereditary Erythrocytosis v1.41 SLC30A10 Arina Puzriakova Gene: slc30a10 has been classified as Amber List (Moderate Evidence).
Hereditary Erythrocytosis v1.40 SLC30A10 Arina Puzriakova Tag treatable tag was added to gene: SLC30A10.
Tag Q4_21_rating tag was added to gene: SLC30A10.
Hereditary Erythrocytosis v1.40 SLC30A10 Arina Puzriakova Phenotypes for gene: SLC30A10 were changed from Erythrocytosis; Polycytemia; Hypermanganesemia; Parkinsonism; Dystonia; Liver disease to Hypermanganesemia with dystonia 1, OMIM:613280; Dystonia/Parkinsonism, Hypermanganesemia, Polycythemia, and Chronic Liver Disease
Likely inborn error of metabolism v2.204 SLC30A10 Arina Puzriakova Phenotypes for gene: SLC30A10 were changed from Parkinson Disease and Complex Parkinsonism; Early onset dystonia; Hypermanganesemia with dystonia 1; Hypermanganesemia with dystonia, polycythemia, and cirrhosis (Disorder of magnesium metabolism) to Hypermanganesemia with dystonia 1, OMIM:613280
Childhood onset dystonia, chorea or related movement disorder v1.205 SLC30A10 Arina Puzriakova Phenotypes for gene: SLC30A10 were changed from Dystonia/Parkinsonism, Hypermanganesemia, Polycythemia, and Chronic Liver Disease; Hypermanganesemia with dystonia, polycythemia, and cirrhosis, 613280 to Hypermanganesemia with dystonia 1, OMIM:613280
Undiagnosed metabolic disorders v1.502 SLC30A10 Arina Puzriakova Phenotypes for gene: SLC30A10 were changed from Hypermanganesemia with dystonia, polycythemia, and cirrhosis (Disorder of magnesium metabolism); Early onset dystonia; Parkinson Disease and Complex Parkinsonism; Hypermanganesemia with dystonia 1 613280 to Hypermanganesemia with dystonia 1, OMIM:613280
Structural basal ganglia disorders v1.27 SLC30A10 Arina Puzriakova Phenotypes for gene: SLC30A10 were changed from to Hypermanganesemia with dystonia 1, OMIM:613280
Neonatal cholestasis v1.21 SLC30A10 Arina Puzriakova Phenotypes for gene: SLC30A10 were changed from Hypermanganesemia with dystonia 1 613280 to Hypermanganesemia with dystonia 1, OMIM:613280
Early onset dystonia v1.103 SLC30A10 Arina Puzriakova Phenotypes for gene: SLC30A10 were changed from Dystonia/Parkinsonism, Hypermanganesemia, Polycythemia, andChronic Liver Disease; Hypermanganesemia with dystonia, polycythemia, and cirrhosis, 613280 to Hypermanganesemia with dystonia 1, OMIM:613280; Dystonia/Parkinsonism, Hypermanganesemia, Polycythemia, and Chronic Liver Disease
Parkinson Disease and Complex Parkinsonism v1.93 SLC30A10 Arina Puzriakova Phenotypes for gene: SLC30A10 were changed from Dystonia/Parkinsonism, Hypermanganesemia, Polycythemia, and Chronic Liver Disease; Dystonia/Parkinsonism, Hypermanganesemia, Polycythemia, andChronic Liver Disease; hypermanganesemia with dystonia-1 (HMNDYT1), increased serum manganese, motor neurodegeneration with extrapyramidal features, polycythemia, and hepatic dysfunction, Brain MRI shows hyperintensities in the basal ganglia to Hypermanganesemia with dystonia 1, OMIM:613280; Dystonia/Parkinsonism, Hypermanganesemia, Polycythemia, and Chronic Liver Disease
Mitochondrial disorders v2.68 OGDH Sarah Leigh Phenotypes for gene: OGDH were changed from Alpha-ketoglutarate dehydrogenase deficiency, 203740 (1) to Alpha-ketoglutarate dehydrogenase deficiency OMIM:203740; oxoglutaricaciduria MONDO:0008759
Mitochondrial disorders v2.67 OGDH Sarah Leigh Mode of inheritance for gene: OGDH was changed from to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v2.66 OGDH Sarah Leigh Classified gene: OGDH as Amber List (moderate evidence)
Mitochondrial disorders v2.66 OGDH Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM. Limited association with OGDH-related mitochondrial disorder in Gen2Phen. PMID: 32383294 reported a single biallelic variant in two sibblings. Functional studies were performed on patient fibroblasts, which demonstrated reduced expression of OGDH and a reduced OGDH complex activity in comparison to the wild type. Drosophila models were constructed which supported the role of the OGDH variant in early developmental lethality.
Mitochondrial disorders v2.66 OGDH Sarah Leigh Gene: ogdh has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v2.65 OGDH Sarah Leigh Publications for gene: OGDH were set to
Mitochondrial disorders v2.64 KIAA0391 Sarah Leigh commented on gene: KIAA0391: PRORP is the HGNC approved gene name for KIAA0391 https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:19958
Mitochondrial disorders v2.64 KIAA0391 Sarah Leigh Tag Q4_21_rating tag was added to gene: KIAA0391.
Mitochondrial disorders v2.64 KIAA0391 Sarah Leigh Classified gene: KIAA0391 as Amber List (moderate evidence)
Mitochondrial disorders v2.64 KIAA0391 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Mitochondrial disorders v2.64 KIAA0391 Sarah Leigh Gene: kiaa0391 has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v2.63 KIAA0391 Sarah Leigh reviewed gene: KIAA0391: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Perrault syndrome clinical spectrum; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v2.63 KIAA0391 Sarah Leigh Tag new-gene-name tag was added to gene: KIAA0391.
Early onset dystonia v1.102 ACTB Sarah Leigh Classified gene: ACTB as Green List (high evidence)
Early onset dystonia v1.102 ACTB Sarah Leigh Added comment: Comment on list classification: Based on the green rating for this gene on https://panelapp.genomicsengland.co.uk/panels/847/gene/ACTB/ and review from Eldar Dedic.
Early onset dystonia v1.102 ACTB Sarah Leigh Gene: actb has been classified as Green List (High Evidence).
Hereditary neuropathy or pain disorder v1.68 MME Lindsey Vialard reviewed gene: MME: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 27588448, 33144514; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Early onset dystonia v1.101 ACTB Sarah Leigh Phenotypes for gene: ACTB were changed from Dystonia, juvenile-onset, 607371Baraitser-Winter syndrome 1, 243310 to Dystonia, juvenile-onset OMIM:607371; developmental malformations-deafness-dystonia syndrome MONDO:0011823; Baraitser-Winter syndrome 1 OMIM:243310; Baraitser-Winter syndrome 1 MONDO:0009470
Early onset dystonia v1.100 ACTB Sarah Leigh Publications for gene: ACTB were set to
Bilateral congenital or childhood onset cataracts v2.94 TCF4 Sarah Leigh Classified gene: TCF4 as Red List (low evidence)
Bilateral congenital or childhood onset cataracts v2.94 TCF4 Sarah Leigh Added comment: Comment on list classification: Single case of paediatric cateracts
Bilateral congenital or childhood onset cataracts v2.94 TCF4 Sarah Leigh Gene: tcf4 has been classified as Red List (Low Evidence).
Bilateral congenital or childhood onset cataracts v2.93 TCF4 Sarah Leigh Added comment: Comment on phenotypes: Variants in TCF4 are associated with Corneal dystrophy, Fuchs endothelial, 3, OMIM:613267, however, this condition does not include cataracts, which associated with TCF4 trinucleotide repeat (RCV000186552.6) in https://doi.org/10.3390/genes12121918.
Bilateral congenital or childhood onset cataracts v2.93 TCF4 Sarah Leigh Phenotypes for gene: TCF4 were changed from Corneal dystrophy, Fuchs endothelial, 3, OMIM:613267 to paediatric cataracts
Bilateral congenital or childhood onset cataracts v2.92 TCF4 Sarah Leigh Publications for gene: TCF4 were set to 29526280; 26401622; 24255041; 25168903; 25722209; 25593321
Bilateral congenital or childhood onset cataracts v2.91 TCF4 Sarah Leigh edited their review of gene: TCF4: Added comment: In https://doi.org/10.3390/genes12121918 (no PMID number available as of 9th December 2021) the authors report TCF4 trinucleotide repeat (RCV000186552.6) in a case Kearns-Sayre Syndrome and corneal endothelial failure and paediatric cataracts.; Changed rating: AMBER; Changed publications to: https://doi.org/10.3390/genes12121918; Changed phenotypes to: paediatric cataracts
Bilateral congenital or childhood onset cataracts v2.91 TCF4 Sarah Leigh Entity copied from Corneal dystrophies v1.8
Bilateral congenital or childhood onset cataracts v2.91 TCF4 Sarah Leigh gene: TCF4 was added
gene: TCF4 was added to Cataracts. Sources: Expert Review Green,Expert list
STR tags were added to gene: TCF4.
Mode of inheritance for gene: TCF4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TCF4 were set to 29526280; 26401622; 24255041; 25168903; 25722209; 25593321
Phenotypes for gene: TCF4 were set to Corneal dystrophy, Fuchs endothelial, 3, OMIM:613267
Corneal dystrophy v1.8 TCF4 Sarah Leigh changed review comment from: Comment on publications: Also https://doi.org/10.3390/genes12121918 (no PMID available 30th Dec 2021).; to: Comment on publications: Also https://doi.org/10.3390/genes12121918 (no PMID available 30th Nov 2021).
Primary lymphoedema v2.23 ANGPT2 Sarah Leigh edited their review of gene: ANGPT2: Changed rating: AMBER
Fetal hydrops v1.45 ANGPT2 Sarah Leigh Tag for-review was removed from gene: ANGPT2.
Fetal hydrops v1.45 ANGPT2 Sarah Leigh Classified gene: ANGPT2 as Amber List (moderate evidence)
Fetal hydrops v1.45 ANGPT2 Sarah Leigh Added comment: Comment on list classification: One biallelic variant in four sibblings in a single family with severe early-onset non-immune hydrops fetalis (pmid 34876502).
Fetal hydrops v1.45 ANGPT2 Sarah Leigh Gene: angpt2 has been classified as Amber List (Moderate Evidence).
Fetal hydrops v1.45 ANGPT2 Sarah Leigh Classified gene: ANGPT2 as Amber List (moderate evidence)
Fetal hydrops v1.45 ANGPT2 Sarah Leigh Added comment: Comment on list classification: One biallelic variant in four sibblings in a single family with severe early-onset non-immune hydrops fetalis (pmid 34876502).
Fetal hydrops v1.45 ANGPT2 Sarah Leigh Gene: angpt2 has been classified as Amber List (Moderate Evidence).
Fetal hydrops v1.44 ANGPT2 Sarah Leigh Entity copied from Primary lymphoedema v2.23
Fetal hydrops v1.44 ANGPT2 Sarah Leigh gene: ANGPT2 was added
gene: ANGPT2 was added to Fetal hydrops. Sources: Expert Review Amber,Literature
for-review tags were added to gene: ANGPT2.
Mode of inheritance for gene: ANGPT2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ANGPT2 were set to 32908006; 34876502
Phenotypes for gene: ANGPT2 were set to Lymphatic malformation 10 OMIM:619369; lymphatic malformation 10 MONDO:0023662
Primary lymphoedema v2.23 ANGPT2 Sarah Leigh edited their review of gene: ANGPT2: Added comment: PMID 34876502 reports four fetuses with hydrops fetalis were homozygous for ANGPT2 NM_001147.2:c.557A>G. The consanguiseious parents and surviving sibblings (a girl and a boy), were heterozygous for this variant. This variant is predicted to create a cryptic exonic splice site, resulting in a r.557_566del and nonsense-mediated mRNA decay. This prediction was supported by the lack of a transcript from this allele in the parents.; Changed rating: GREEN; Changed publications to: 34876502; Changed phenotypes to: severe early-onset non-immune hydrops fetalis; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary lymphoedema v2.23 ANGPT2 Sarah Leigh Publications for gene: ANGPT2 were set to 32908006
Primary lymphoedema v2.22 ANGPT2 Sarah Leigh Added comment: Comment on phenotypes: Biallelic variants reported in severe early-onset non-immune hydrops fetalis (PMID 34876502).
Primary lymphoedema v2.22 ANGPT2 Sarah Leigh Phenotypes for gene: ANGPT2 were changed from Lymphatic malformation 10 OMIM:619369; lymphatic malformation 10 MONDO:0023662 to Lymphatic malformation 10 OMIM:619369; lymphatic malformation 10 MONDO:0023662
Primary lymphoedema v2.21 ANGPT2 Sarah Leigh Phenotypes for gene: ANGPT2 were changed from Primary lymphoedema to Lymphatic malformation 10 OMIM:619369; lymphatic malformation 10 MONDO:0023662
Early onset dystonia v1.99 GCDH Eldar Dedic reviewed gene: GCDH: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 21912879, 33064266; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Erythrocytosis v1.39 PIEZO1 Arina Puzriakova Phenotypes for gene: PIEZO1 were changed from Erythrocytosis to Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema, OMIM:194380; Erythrocytosis
Primary lymphoedema v2.20 PIEZO1 Arina Puzriakova Added comment: Comment on mode of inheritance: MOI should be updated from 'Both mono- and biallelic' to 'Biallelic' only at the next GMS review. Monoallelic variants are associated with hereditary xerocytosis (MIM# 194380), a phenotype that is not relevant to this panel.
Primary lymphoedema v2.20 PIEZO1 Arina Puzriakova Mode of inheritance for gene: PIEZO1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Primary lymphoedema v2.19 PIEZO1 Arina Puzriakova Tag Q4_21_MOI tag was added to gene: PIEZO1.
Primary lymphoedema v2.19 PIEZO1 Arina Puzriakova Phenotypes for gene: PIEZO1 were changed from Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema 194380; Lymphatic malformation 6 616843 to Lymphatic malformation 6, OMIM:616843
Rare anaemia v1.31 PIEZO1 Arina Puzriakova Phenotypes for gene: PIEZO1 were changed from Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema, OMIM:194380; Lymphatic malformation 6, OMIM:616843; Hereditary xerocytosis to Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema, OMIM:194380; Hereditary xerocytosis
Rare anaemia v1.30 PIEZO1 Arina Puzriakova Phenotypes for gene: PIEZO1 were changed from 194380 Stomatocytosis; 616843 Lymphatic malformation 6; 194380 Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema; Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema; Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema, 194380; Stomatocytosis; Hereditary xerocytosis; Dehydrated hereditary stomatocytosis to Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema, OMIM:194380; Lymphatic malformation 6, OMIM:616843; Hereditary xerocytosis
Cytopenias and congenital anaemias v1.93 PIEZO1 Arina Puzriakova Phenotypes for gene: PIEZO1 were changed from Stomatocytosis; Dehydrated hereditary stomatocytosis; Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema, 194380; Hereditary xerocytosis to Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema, OMIM:194380; Hereditary xerocytosis
Fetal anomalies v1.820 PIEZO1 Arina Puzriakova Phenotypes for gene: PIEZO1 were changed from hydrops fetalis gene 616843; Congenital lymphatic dysplasia with hydrops and/or lymphoedema to Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema, OMIM:194380; Lymphatic malformation 6, OMIM:616843; Congenital lymphatic dysplasia with hydrops and/or lymphoedema
Fetal hydrops v1.43 PIEZO1 Arina Puzriakova Phenotypes for gene: PIEZO1 were changed from Lymphedema, hereditary, III, 616843; LMPH3; Hereditary lymphoedema type III; 2nd trimester fetal hydrops, Nuchal translucency likely to be normal, Lethal and non lethal cases within the same family to Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema, OMIM:194380; Lymphatic malformation 6, OMIM:616843; Congenital lymphatic dysplasia with hydrops and/or lymphoedema
Hereditary Erythrocytosis v1.38 SH2B3 Arina Puzriakova Publications for gene: SH2B3 were set to 23812944; 20843259
Hereditary Erythrocytosis v1.37 BPGM Arina Puzriakova Publications for gene: BPGM were set to 27651169; 25015942; 5799137; 1421379; 15054810
Hereditary Erythrocytosis v1.36 BPGM Arina Puzriakova Tag Q4_21_expert_review tag was added to gene: BPGM.
Tag Q4_21_MOI tag was added to gene: BPGM.
Tag Q4_21_rating tag was added to gene: BPGM.
Hereditary Erythrocytosis v1.36 BPGM Arina Puzriakova Added comment: Comment on mode of inheritance: Three patients described in literature with biallelic variants (PMID: 1421379; 15054810; 33216349) and 2 with heterozygous variants (PMID: 25015942; 27651169) in the BPGM gene. Heterozygous variants in some cases may cause milder erythrocytosis due to partial BPGM deficiency.

Of the four individuals (2 homo, 2 het) identified in the paper reviewed by Dmitrijs Rots (PMID: 29790589), three variants were classified VUS and the other had been previously reported and therefore these cases could not be included.

Although the number of monoallelic cases does not reach the threshold for inclusion, the evidence supports an association with erythrocytosis. To reduce risk of potentially missed diagnoses the MOI may be considered for update from 'biallelic' to 'both mono- and biallelic' but this will be flagged for further GMS review.

In any case, BPGM should be promoted to Green at the next GMS panel update with the respective MOI based on the decision of the expert working group.
Hereditary Erythrocytosis v1.36 BPGM Arina Puzriakova Mode of inheritance for gene: BPGM was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Cytopenia - NOT Fanconi anaemia v1.50 POLR2C Ivone Leong Phenotypes for gene: POLR2C were changed from Primary ovarian insufficiency to thrombocytopenia, MONDO:0002049
Cytopenias and congenital anaemias v1.92 POLR2C Ivone Leong Phenotypes for gene: POLR2C were changed from thrombocytopenia, to thrombocytopenia, MONDO:0002049
Cytopenias and congenital anaemias v1.91 POLR2C Ivone Leong Phenotypes for gene: POLR2C were changed from thrombocytopenia, to thrombocytopenia,
Cytopenias and congenital anaemias v1.91 POLR2C Ivone Leong Phenotypes for gene: POLR2C were changed from Primary ovarian insufficiency to thrombocytopenia,
Congenital hypothyroidism v2.8 POLR2C Ivone Leong Phenotypes for gene: POLR2C were changed from Primary ovarian insufficiency to hypothyroidism, MONDO:0005420
Congenital hypothyroidism v2.7 POLR2C Ivone Leong Classified gene: POLR2C as Red List (low evidence)
Congenital hypothyroidism v2.7 POLR2C Ivone Leong Gene: polr2c has been classified as Red List (Low Evidence).
Congenital hypothyroidism v2.6 POLR2C Ivone Leong Tag watchlist was removed from gene: POLR2C.
Congenital hypothyroidism v2.6 POLR2C Ivone Leong changed review comment from: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is not associated with a phenotype in OMIM or Gene2Phenotype. The affected patients in PMID: 29367954 also had hypothyroidism (3/5), thrombocytopenia (2/5) and pernicious anaemia (2/5).; to: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is not associated with a phenotype in OMIM or Gene2Phenotype. The affected patients in PMID: 29367954 also had hypothyroidism (3/5), thrombocytopenia (2/5) and pernicious anaemia (2/5). The entries in ClinVar did not mention any other phenotype. So therefore this gene has been given a Red rating.
Cytopenia - NOT Fanconi anaemia v1.49 POLR2C Ivone Leong Classified gene: POLR2C as Red List (low evidence)
Cytopenia - NOT Fanconi anaemia v1.49 POLR2C Ivone Leong Gene: polr2c has been classified as Red List (Low Evidence).
Cytopenia - NOT Fanconi anaemia v1.48 POLR2C Ivone Leong changed review comment from: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is not associated with a phenotype in OMIM or Gene2Phenotype. The affected patients in PMID: 29367954 also had hypothyroidism (3/5), thrombocytopenia (2/5) and pernicious anaemia (2/5).; to: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is not associated with a phenotype in OMIM or Gene2Phenotype. The affected patients in PMID: 29367954 also had hypothyroidism (3/5), thrombocytopenia (2/5) and pernicious anaemia (2/5). The entries in ClinVar did not mention any other phenotype. So therefore this gene has been given a Red rating.
Cytopenia - NOT Fanconi anaemia v1.48 POLR2C Ivone Leong Tag watchlist was removed from gene: POLR2C.
Cytopenias and congenital anaemias v1.90 POLR2C Ivone Leong Classified gene: POLR2C as Red List (low evidence)
Cytopenias and congenital anaemias v1.90 POLR2C Ivone Leong Gene: polr2c has been classified as Red List (Low Evidence).
Primary ovarian insufficiency v1.62 POLR2C Ivone Leong changed review comment from: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is not associated with a phenotype in OMIM or Gene2Phenotype. The affected patients in PMID: 29367954 also had hypothyroidism (3/5), thrombocytopenia (2/5) and pernicious anaemia (2/5).; to: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is not associated with a phenotype in OMIM or Gene2Phenotype. The affected patients in PMID: 29367954 also had hypothyroidism (3/5), thrombocytopenia (2/5) and pernicious anaemia (2/5). There is currently not enough evidence to support a gene-disease association. This gene has been given an Amber rating.
Cytopenias and congenital anaemias v1.89 POLR2C Ivone Leong changed review comment from: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is not associated with a phenotype in OMIM or Gene2Phenotype. The affected patients in PMID: 29367954 also had hypothyroidism (3/5), thrombocytopenia (2/5) and pernicious anaemia (2/5).; to: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is not associated with a phenotype in OMIM or Gene2Phenotype. The affected patients in PMID: 29367954 also had hypothyroidism (3/5), thrombocytopenia (2/5) and pernicious anaemia (2/5). The entries in ClinVar did not mention any other phenotype. So therefore this gene has been given a Red rating.
Cytopenias and congenital anaemias v1.89 POLR2C Ivone Leong Tag watchlist was removed from gene: POLR2C.
Cytopenias and congenital anaemias v1.89 POLR2C Ivone Leong Entity copied from Primary ovarian insufficiency v1.62
Cytopenias and congenital anaemias v1.89 POLR2C Ivone Leong gene: POLR2C was added
gene: POLR2C was added to Cytopenias and congenital anaemias. Sources: Literature,Expert Review Amber
watchlist tags were added to gene: POLR2C.
Mode of inheritance for gene: POLR2C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POLR2C were set to 34794894; 29367954
Phenotypes for gene: POLR2C were set to Primary ovarian insufficiency
Cytopenia - NOT Fanconi anaemia v1.48 POLR2C Ivone Leong Entity copied from Primary ovarian insufficiency v1.62
Cytopenia - NOT Fanconi anaemia v1.48 POLR2C Ivone Leong gene: POLR2C was added
gene: POLR2C was added to Cytopenia - NOT Fanconi anaemia. Sources: Expert Review Amber,Literature
watchlist tags were added to gene: POLR2C.
Mode of inheritance for gene: POLR2C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POLR2C were set to 34794894; 29367954
Phenotypes for gene: POLR2C were set to Primary ovarian insufficiency
Congenital hypothyroidism v2.6 POLR2C Ivone Leong Entity copied from Primary ovarian insufficiency v1.62
Congenital hypothyroidism v2.6 POLR2C Ivone Leong gene: POLR2C was added
gene: POLR2C was added to Congenital hypothyroidism. Sources: Expert Review Amber,Literature
watchlist tags were added to gene: POLR2C.
Mode of inheritance for gene: POLR2C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POLR2C were set to 34794894; 29367954
Phenotypes for gene: POLR2C were set to Primary ovarian insufficiency
Primary ovarian insufficiency v1.62 POLR2C Ivone Leong Classified gene: POLR2C as Amber List (moderate evidence)
Primary ovarian insufficiency v1.62 POLR2C Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is not associated with a phenotype in OMIM or Gene2Phenotype. The affected patients in PMID: 29367954 also had hypothyroidism (3/5), thrombocytopenia (2/5) and pernicious anaemia (2/5).
Primary ovarian insufficiency v1.62 POLR2C Ivone Leong Gene: polr2c has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v1.68 RFC1 Eleanor Williams commented on gene: RFC1: Copied this gene from the Hereditary ataxia - adult onset panel so that it is noted that the STR associated with this gene is relevant to the panel, NOT SNV/indels or deletions covering this gene. In PMID: 33969391 - Curro et al 2021 - they found that 43 patients (34%) with sensory neuropathy had biallelic AAGGG repeat expansions in RFC1and in none with sensory-motor neuropathy.
Primary ovarian insufficiency v1.61 POLR2C Ivone Leong Tag watchlist tag was added to gene: POLR2C.
Hereditary neuropathy or pain disorder v1.68 RFC1 Eleanor Williams Entity copied from Hereditary ataxia - adult onset v2.134
Hereditary neuropathy or pain disorder v1.68 RFC1 Eleanor Williams gene: RFC1 was added
gene: RFC1 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: Expert Review Red,Expert Review
STR tags were added to gene: RFC1.
Mode of inheritance for gene: RFC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RFC1 were set to 30926972; 31824583; 32851396; 32582864; 33969391
Phenotypes for gene: RFC1 were set to Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome, OMIM:614575; cerebellar ataxia, neuropathy, and vestibular areflexia syndrome, MONDO:0013809; chronic idiopathic axonal polyneuropathy; chronic polyneuropathy, MONDO:0003335
Mode of pathogenicity for gene: RFC1 was set to Other
Hereditary ataxia with onset in adulthood v2.134 RFC1 Eleanor Williams Classified gene: RFC1 as Red List (low evidence)
Hereditary ataxia with onset in adulthood v2.134 RFC1 Eleanor Williams Added comment: Comment on list classification: Changing the rating from amber to red so that it is clear that this gene should not be added to the panel as it is an STR within an intron of this gene that is associated with the neuropathy phenotype.
Hereditary ataxia with onset in adulthood v2.134 RFC1 Eleanor Williams Gene: rfc1 has been classified as Red List (Low Evidence).
DDG2P v2.55 PBX1 Eleanor Williams Classified gene: PBX1 as No list
DDG2P v2.55 PBX1 Eleanor Williams Added comment: Comment on list classification: Changing the status to Expert Review Removed, as the content of the panel is only changed when updated from DDG2P sources. The status of this gene on other panels has been checked.
DDG2P v2.55 PBX1 Eleanor Williams Gene: pbx1 has been removed from the panel.
DDG2P v2.54 PBX1 Eleanor Williams Tag curated_removed tag was added to gene: PBX1.
DDG2P v2.54 PBX1 Eleanor Williams Classified gene: PBX1 as No list
DDG2P v2.54 PBX1 Eleanor Williams Gene: pbx1 has been removed from the panel.
DDG2P v2.53 PBX1 Eleanor Williams commented on gene: PBX1
Monogenic hearing loss v2.214 PBX1 Eleanor Williams Publications for gene: PBX1 were set to 28566479; 29036646
Monogenic hearing loss v2.213 PBX1 Eleanor Williams Mode of inheritance for gene: PBX1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Monogenic hearing loss v2.212 PBX1 Eleanor Williams Tag Q4_21_rating tag was added to gene: PBX1.
Monogenic hearing loss v2.212 PBX1 Eleanor Williams changed review comment from: Comment on list classification: Promoting from grey to amber. 3 cases but in 1 case 7 other genes also deleted, and in another hearing loss was unilateral only.; to: Comment on list classification: Promoting from grey to amber. Deletions affecting more than just the PBX1 gene is reported for many, but in 3 cases only the PBX1 gene is affected. Recommend green rating following GMS review.
Monogenic hearing loss v2.212 PBX1 Eleanor Williams changed review comment from: Associated with Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay #617641 (AD) in OMIM.

3 cases with reported hearing loss among other anomalies, but in one case a further 7 genes are deleted, and in one case the hearing loss was unilateral only.

PMID: 28566479 - Heidet et al 2017 - performed targeted exome screening of candidate 330 genes in a cohort of 204 patients with CAKUT and 11 patients suspected to suffer from branchio-oto-renal syndrome. 2 out of 5 patients with heterozygous loss of function mutations/deletions in PBX1 are reported to have deafness in addition to a renal phenotype. In patient K175 there was a de novo heterozygous 1 bp deletion leading to a frameshift. In patient K1819 there was a de novo 2.46-Mb deletion removing the whole PBX1 gene along with 7 other genes. Further details about the loss of hearing phenotype are not given.

PMID: 29036646 - Slavotinek et al 2017 - report 8 patients with de novo, deleterious sequence variants in the PBX1. 3 had external ear abnormalities but only 1 is reported to have hearing loss and this is unilateral, mild to moderate conductive hearing loss. This patient was found to have a heterozygous, de novo indel c.783dupC, predicting (p.Ser262Glnfs*2 in PBX1.; to: Associated with Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay #617641 (AD) in OMIM.

3 cases reported where only the PBX1 gene is affected (indels or deletion covering only the PBX1 gene). In one of these cases the phenotype is syndromic but hearing loss is unilateral only. In 5 further cases hearing loss is reported and involve microdeletions covering more genes that just PBX1.

PMID: 28566479 - Heidet et al 2017 - performed targeted exome screening of candidate 330 genes in a cohort of 204 patients with CAKUT and 11 patients suspected to suffer from branchio-oto-renal syndrome. 2 out of 5 patients with heterozygous loss of function mutations/deletions in PBX1 are reported to have deafness in addition to a renal phenotype. In patient K175 there was a de novo heterozygous 1 bp deletion leading to a frameshift. In patient K1819 there was a de novo 2.46-Mb deletion removing the whole PBX1 gene along with 7 other genes. Further details about the loss of hearing phenotype are not given.

PMID: 29036646 - Slavotinek et al 2017 - report 8 patients with de novo, deleterious sequence variants in the PBX1. 3 had external ear abnormalities but only 1 is reported to have hearing loss and this is unilateral, mild to moderate conductive hearing loss. This patient was found to have a heterozygous, de novo indel c.783dupC, predicting (p.Ser262Glnfs*2 in PBX1.

PMID: 28270404 - Le Tanno et al 2017 - eight patients presenting with CAKUT carrying an 1q23.3q24.1 microdeletion. They defined a 276-kb minimal common region that only overlaps with the PBX1 gene. 5 patients presented with varying degrees of hearing impairment (no detailed assessments). Patient 8, in which the deletion only covers the PBX1 gene showed an obvious bilateral dysplasia leading to a conductive hearing defect.
Early onset dystonia v1.99 GAMT Eldar Dedic reviewed gene: GAMT: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 19027335, 33996490, 12557293, 19288536, 16855203; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
DDG2P v2.53 PBX1 Eleanor Williams Deleted their review
DDG2P v2.53 PBX1 Eleanor Williams Deleted their comment
DDG2P v2.53 PBX1 Eleanor Williams commented on gene: PBX1
Monogenic hearing loss v2.212 PBX1 Eleanor Williams Classified gene: PBX1 as Amber List (moderate evidence)
Monogenic hearing loss v2.212 PBX1 Eleanor Williams Added comment: Comment on list classification: Promoting from grey to amber. 3 cases but in 1 case 7 other genes also deleted, and in another hearing loss was unilateral only.
Monogenic hearing loss v2.212 PBX1 Eleanor Williams Gene: pbx1 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.211 PBX1 Eleanor Williams Phenotypes for gene: PBX1 were changed from Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay to Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay, OMIM:617641; congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay, MONDO:0060549
Monogenic hearing loss v2.210 PBX1 Eleanor Williams Publications for gene: PBX1 were set to
Monogenic hearing loss v2.209 PBX1 Eleanor Williams reviewed gene: PBX1: Rating: ; Mode of pathogenicity: None; Publications: 28566479, 29036646; Phenotypes: Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay, OMIM:617641; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy v2.478 BET1 Dmitrijs Rots gene: BET1 was added
gene: BET1 was added to Genetic epilepsy syndromes. Sources: Literature
Mode of inheritance for gene: BET1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BET1 were set to PMID: 34779586
Phenotypes for gene: BET1 were set to Epilepsy; congenical musculara dystrophy
Penetrance for gene: BET1 were set to Complete
Review for gene: BET1 was set to GREEN
Added comment: 3 reported individuals from two families with biallelic variants and functional data supporting the role of the variants in the phenotype. Enough evidence for green rating.
Sources: Literature
Congenital muscular dystrophy v2.21 BET1 Dmitrijs Rots reviewed gene: BET1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34779586; Phenotypes: Congenital muscular dystrophy, epilepsy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary ovarian insufficiency v1.61 POLR3H Ivone Leong Tag watchlist tag was added to gene: POLR3H.
Primary ovarian insufficiency v1.61 POLR3H Ivone Leong Classified gene: POLR3H as Amber List (moderate evidence)
Primary ovarian insufficiency v1.61 POLR3H Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is not associated with a phenotype in Gene2Phenotype and it is not present in OMIM. There is currently not enough evidence to support a gene-disease association. This gene has been given an Amber rating.
Primary ovarian insufficiency v1.61 POLR3H Ivone Leong Gene: polr3h has been classified as Amber List (Moderate Evidence).
Cardiac arrhythmias - additional genes v1.14 GNB5 Arina Puzriakova Classified gene: GNB5 as Amber List (moderate evidence)
Cardiac arrhythmias - additional genes v1.14 GNB5 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update. >3 unrelated families with cardiac arrhythmia identified, which may be the main presenting feature. This also may be the most likely route for testing in some cases, particularly where no seizures and only mild cognitive impairment are observed.
Cardiac arrhythmias - additional genes v1.14 GNB5 Arina Puzriakova Gene: gnb5 has been classified as Amber List (Moderate Evidence).
Corneal dystrophy v1.8 TCF4 Ivone Leong Phenotypes for gene: TCF4 were changed from Corneal dystrophy, Fuchs endothelial, 3, 613267 to Corneal dystrophy, Fuchs endothelial, 3, OMIM:613267
Optic neuropathy v2.54 ALPK1 Ivone Leong Phenotypes for gene: ALPK1 were changed from Retinopathy; Optic disc swelling; Splenomegaly; Pancytopenia; Headaches; ocular inflammation. to ROSAH syndrome, OMIM:614979
Optic neuropathy v2.53 ALPK1 Ivone Leong Classified gene: ALPK1 as Amber List (moderate evidence)
Optic neuropathy v2.53 ALPK1 Ivone Leong Added comment: Comment on list classification: New gene added by Neringa Jurkute (MD). This gene is associated with a phenotype in OMIM and Gene2Phenotype (Strong). There is enough evidence to support a gene-disease assocation. This gene should be rated Green at the next review.
Optic neuropathy v2.53 ALPK1 Ivone Leong Gene: alpk1 has been classified as Amber List (Moderate Evidence).
Optic neuropathy v2.52 ALPK1 Ivone Leong Tag Q4_21_rating tag was added to gene: ALPK1.
Tag Q4_21_NHS_review tag was added to gene: ALPK1.
Optic neuropathy v2.52 ALPK1 Ivone Leong Publications for gene: ALPK1 were set to PMID: 30967659; 31053777; 31939038; 34159509
Retinal disorders v2.239 ALPK1 Ivone Leong Tag Q4_21_NHS_review tag was added to gene: ALPK1.
Retinal disorders v2.239 ALPK1 Ivone Leong Added comment: Comment on publications: Added new publication (PMID:31053777;34159509).
Retinal disorders v2.239 ALPK1 Ivone Leong Publications for gene: ALPK1 were set to 30967659; 31939038
Retinal disorders v2.238 HKDC1 Ivone Leong Classified gene: HKDC1 as Red List (low evidence)
Retinal disorders v2.238 HKDC1 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype (limited). PMID: 30085091 also describes a mouse knockout model. In the mouse model, the retinal degeneration phenotypes were mild (like that seen in humans) and did not have retinal phenotypes until 9 months (similar to the late onset in humans). There is currently not enough evidence to support a gene-disease association. This gene is borderline Red/Amber.
Retinal disorders v2.238 HKDC1 Ivone Leong Gene: hkdc1 has been classified as Red List (Low Evidence).
Cardiac arrhythmias - additional genes v1.13 GNB5 Arina Puzriakova gene: GNB5 was added
gene: GNB5 was added to Cardiac arrhythmias - additional genes. Sources: Literature
Q4_21_rating tags were added to gene: GNB5.
Mode of inheritance for gene: GNB5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GNB5 were set to 27523599; 28697420; 29368331; 33172956
Phenotypes for gene: GNB5 were set to Intellectual developmental disorder with cardiac arrhythmia, OMIM:617173; Language delay and ADHD/cognitive impairment with or without cardiac arrhythmia, OMIM:617182
Review for gene: GNB5 was set to GREEN
Added comment: Biallelic GNB5 pathogenic variants cause two relevant phenotypes: intellectual developmental disorder with cardiac arrhythmia (MIM 617173) or language delay and ADHD/cognitive impairment with or without cardiac arrhythmia (MIM 617182).

Heart rate disturbances (in most cases reminiscent of sick sinus syndrome) have been reported as a feature of both disorders. At least 8 unrelated families with arrhythmias associated with variants in this gene reported in literature. Cardiac involvement supported by animal model studies.
Sources: Literature
Retinal disorders v2.237 HKDC1 Ivone Leong Phenotypes for gene: HKDC1 were changed from Retinitis pigmentosa 92, MIM# 619614 to Retinitis pigmentosa 92, OMIM:619614
Intellectual disability v3.1479 GNB5 Arina Puzriakova Phenotypes for gene: GNB5 were changed from Language delay and ADHD/cognitive impairment with or without cardiac arrhythmia, 617182; Intellectual developmental disorder with cardiac arrhythmia, 617173 to Intellectual developmental disorder with cardiac arrhythmia, OMIM:617173; Language delay and ADHD/cognitive impairment with or without cardiac arrhythmia, OMIM:617182
Early onset or syndromic epilepsy v2.478 GNB5 Arina Puzriakova Phenotypes for gene: GNB5 were changed from Intellectual developmental disorder with cardiac arrhythmia, 617173; Language delay and ADHD/cognitive impairment with or without cardiac arrhythmia, 617182; early infantile epileptic encephalopathy (EIEE) to Intellectual developmental disorder with cardiac arrhythmia, OMIM:617173
Early onset dystonia v1.99 FOXG1 Eldar Dedic changed review comment from: Dzinovic, et al. (2021, PMID: 34399161) analyzed 45 pediatric complex dystonia cases. The whole-exome-sequencing revealed de novo heterozygous FOXG1 c.703C >T (p.Leu235Phe) variant in 3 years of age female case of European ethnicity. Parents were Sanger sequenced.

- Please note that FOXG1 c.703C >T (p.Leu235Phe) variant was absent from gnomAD v2.1.1 as of December 2021

Wong, et al. (2019, PMID: 31316448) analyzed 30 cases with encephalopathy and movement impairments. Whole-exome-sequencing revealed 3 variants (c.763 T>C (p.Trp255Arg); c.250delC (p.Gln86Argfs*106); c.256dupC (p.Gln86Aspfs*34)) in FOXG1 gene in 3 Han Chinese cases (between 2 and 17 years of age) from Taiwan who had dystonia , respectively (Table 1).

- Please note that FOXG1 c.250delC (p.Gln86Argfs*106) variant was filtered from gnomAD v2.1.1, while FOXG1 c.763 T>C (p.Trp255Arg) and FOXG1 c.256dupC (p.Gln86Aspfs*34) variants were absent from gnomAD v2.1.1 as of December 2021

Mencarelli, et al. (2010, PMID: 19578037) analyzed 107 cases of European origin (including 60 Rett syndrome (RTT), 43 encephalopathy, and 4 RTT-like patients). The FOXG1 c.643T>C (p.Phe215Leu) variant has been found de novo in one 8 years of age female RTT patient with dystonia (diagnosed at 2 years of age) of French origin.

- Please note that FOXG1 c.643T>C (p.Phe215Leu) variant was absent from gnomAD v2.1.1 as of December 2021; to: Dzinovic, et al. (2021, PMID: 34399161) analyzed 45 pediatric complex dystonia cases. The whole-exome-sequencing revealed de novo heterozygous FOXG1 c.703C >T (p.Leu235Phe) variant in 3 years of age female case of European ethnicity. Parents were Sanger sequenced.

- Please note that FOXG1 c.703C >T (p.Leu235Phe) variant was absent from gnomAD v2.1.1 as of December 2021

Wong, et al. (2019, PMID: 31316448) analyzed 30 cases with encephalopathy and movement impairments. Whole-exome-sequencing revealed 3 variants (c.763 T>C (p.Trp255Arg); c.250delC (p.Gln86Argfs*106); c.256dupC (p.Gln86Aspfs*34)) in FOXG1 gene in 3 Han Chinese cases (between 2 and 17 years of age) from Taiwan who had dystonia, respectively (Table 1).

- Please note that FOXG1 c.250delC (p.Gln86Argfs*106) variant was filtered from gnomAD v2.1.1, while FOXG1 c.763 T>C (p.Trp255Arg) and FOXG1 c.256dupC (p.Gln86Aspfs*34) variants were absent from gnomAD v2.1.1 as of December 2021

Mencarelli, et al. (2010, PMID: 19578037) analyzed 107 cases of European origin (including 60 Rett syndrome (RTT), 43 encephalopathy, and 4 RTT-like patients). The FOXG1 c.643T>C (p.Phe215Leu) variant has been found de novo in one 8 years of age female RTT patient with dystonia (diagnosed at 2 years of age) of French origin.

- Please note that FOXG1 c.643T>C (p.Phe215Leu) variant was absent from gnomAD v2.1.1 as of December 2021
Early onset dystonia v1.99 FOXG1 Eldar Dedic reviewed gene: FOXG1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34399161, 31316448, 19578037; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Malformations of cortical development v2.112 NPRL2 Ivone Leong Penetrance for gene NPRL2 was set from to None
Malformations of cortical development v2.111 NPRL2 Ivone Leong Classified gene: NPRL2 as Amber List (moderate evidence)
Malformations of cortical development v2.111 NPRL2 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in OMIM but not Gene2Phenotype. It should be noted that not all patients with variants in this gene has focal cortical dysplasia; however, there is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Malformations of cortical development v2.111 NPRL2 Ivone Leong Gene: nprl2 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.110 NPRL2 Ivone Leong Tag Q4_21_rating tag was added to gene: NPRL2.
Malformations of cortical development v2.110 NPRL2 Ivone Leong Added comment: Comment on publications: PMID: 30093711 describes another 2 cases with FCD.
Malformations of cortical development v2.110 NPRL2 Ivone Leong Publications for gene: NPRL2 were set to 29281825; 27173016; 31625153
Optic neuropathy v2.51 ALPK1 Neringa Jurkute changed review comment from: Recurrent variant has been reported in affected individuals from 9 unrelated families. Affected individual shared overlapping phenotype with retinal dystrophy, chronic disc swelling observed in majority of cases.
Sources: Literature, Research, Other; to: Recurrent variant has been reported in affected individuals from 9 unrelated families. Affected individuals shared overlapping phenotype with retinal changes, chronic disc swelling observed in majority of cases.

OMIM: 614979
PMID: 30967659; 31053777; 31939038; 34159509
Sources: Literature, Research, Other
Retinal disorders v2.236 ALPK1 Neringa Jurkute changed review comment from: Recurrent variant has been reported in affected individuals from 9 unrelated families. Affected individuals shared overlapping phenotype with retinal dystrophy, chronic disc swelling observed in majority of cases.

PMID: 30967659; 31053777; 31939038; 34159509; to: Recurrent variant has been reported in affected individuals from 9 unrelated families. Affected individuals shared overlapping phenotype with retinal changes, chronic disc swelling observed in majority of cases.

OMIM: 614979

PMID: 30967659; 31053777; 31939038; 34159509
Retinal disorders v2.236 ALPK1 Neringa Jurkute changed review comment from: Recurrent variant has been reported in affected individuals from 9 unrelated families. Affected individual shared overlapping phenotype with retinal dystrophy, chronic disc swelling observed in majority of cases.

PMID: 30967659; 31053777; 31939038; 34159509; to: Recurrent variant has been reported in affected individuals from 9 unrelated families. Affected individuals shared overlapping phenotype with retinal dystrophy, chronic disc swelling observed in majority of cases.

PMID: 30967659; 31053777; 31939038; 34159509
Retinal disorders v2.236 ALPK1 Neringa Jurkute reviewed gene: ALPK1: Rating: GREEN; Mode of pathogenicity: Other; Publications: 30967659, 31053777, 31939038, 34159509; Phenotypes: Retinal dystrophy, optic disc swelling, splenomegaly, headaches, ocular inflammation; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Malformations of cortical development v2.109 NPRL2 Ivone Leong Phenotypes for gene: NPRL2 were changed from Epilepsy, familial focal, with variable foci 2, MIM# 617116 to Epilepsy, familial focal, with variable foci 2, OMIM:617116
Optic neuropathy v2.51 ALPK1 Neringa Jurkute changed review comment from: Recurrent variant has been reported in affected individuals from 9 unrelated families. Affected individual shared overlapping phenotype with retinal dystrophy, chronic disc swelling observed in majority of cases.
Sources: Literature, Research, Other; to: Recurrent variant has been reported in affected individuals from 9 unrelated families. Affected individual shared overlapping phenotype with retinal dystrophy, chronic disc swelling observed in majority of cases.
Sources: Literature, Research, Other
Optic neuropathy v2.51 ALPK1 Neringa Jurkute gene: ALPK1 was added
gene: ALPK1 was added to Optic neuropathy. Sources: Literature,Research,Other
Mode of inheritance for gene: ALPK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ALPK1 were set to PMID: 30967659; 31053777; 31939038; 34159509
Phenotypes for gene: ALPK1 were set to Retinopathy; Optic disc swelling; Splenomegaly; Pancytopenia; Headaches; ocular inflammation.
Mode of pathogenicity for gene: ALPK1 was set to Other
Review for gene: ALPK1 was set to GREEN
Added comment: Recurrent variant has been reported in affected individuals from 9 unrelated families. Affected individual shared overlapping phenotype with retinal dystrophy, chronic disc swelling observed in majority of cases.
Sources: Literature, Research, Other
Malformations of cortical development v2.108 GRIN2B Ivone Leong Classified gene: GRIN2B as Amber List (moderate evidence)
Malformations of cortical development v2.108 GRIN2B Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Malformations of cortical development v2.108 GRIN2B Ivone Leong Gene: grin2b has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.107 GRIN2B Ivone Leong Tag Q4_21_rating tag was added to gene: GRIN2B.
Malformations of cortical development v2.107 GRIN2B Ivone Leong Phenotypes for gene: GRIN2B were changed from Mental retardation, autosomal dominant 6, MIM# 613970 to Intellectual developmental disorder, autosomal dominant 6, with or without seizures, OMIM:613970
Malformations of cortical development v2.106 SCN3A Ivone Leong Classified gene: SCN3A as Amber List (moderate evidence)
Malformations of cortical development v2.106 SCN3A Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in OMIM and Gene2Phenotype (Strong). PMID: 34081427 reports that 31/38 (82%) cases have malformation of cortical development. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Malformations of cortical development v2.106 SCN3A Ivone Leong Gene: scn3a has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.105 SCN3A Ivone Leong Tag Q4_21_rating tag was added to gene: SCN3A.
Malformations of cortical development v2.105 SCN3A Ivone Leong Publications for gene: SCN3A were set to 32515017; 30146301
Malformations of cortical development v2.104 SCN3A Ivone Leong Phenotypes for gene: SCN3A were changed from Polymicrogyria; malformations of cortical development; epilepsy to Polymicrogyria, MONDO:0000087; malformations of cortical development; epilepsy, MONDO:0005027; Developmental and epileptic encephalopathy 62, OMIM:617938
Malformations of cortical development v2.103 ATP1A3 Ivone Leong Phenotypes for gene: ATP1A3 were changed from Polymicrogyria; epilepsy; developmental delay to Polymicrogyria, MONDO:0000087; epilepsy, MONDO:0005027; developmental delay; Developmental and epileptic encephalopathy 99, OMIM:619606
Malformations of cortical development v2.102 ATP1A3 Ivone Leong Classified gene: ATP1A3 as Amber List (moderate evidence)
Malformations of cortical development v2.102 ATP1A3 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in OMIM and Gene2Phenotype. PMID:33880529 describes additional cases of patients with variants in ATP1A3 who have polymicrogyria. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Malformations of cortical development v2.102 ATP1A3 Ivone Leong Gene: atp1a3 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.101 ATP1A3 Ivone Leong Publications for gene: ATP1A3 were set to 33762331
Malformations of cortical development v2.100 ATP1A3 Ivone Leong Tag Q4_21_rating tag was added to gene: ATP1A3.
Familial dysautonomia v1.15 PHOX2B Arina Puzriakova Tag currently-ngs-unreportable was removed from gene: PHOX2B.
Early onset dystonia v1.99 ARX Eldar Dedic reviewed gene: ARX: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31324350, 29778428, 23657928, 29343471; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Early onset dystonia v1.99 ACTB Eldar Dedic reviewed gene: ACTB: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 31970217, 29788902, 28849312, 27862284, 29220674, 25255767; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset dystonia v1.99 ACTB Eldar Dedic Deleted their review
Early onset dystonia v1.99 ACTB Eldar Dedic Deleted their comment
Early onset dystonia v1.99 AFG3L2 Eldar Dedic reviewed gene: AFG3L2: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 32219868; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Brain channelopathy v1.70 CACNA1A Zornitza Stark changed review comment from: Four infants, all presenting with hypotonia, mild facial dysmorphic features, encephalopathy, and seizures, born
to consanguineous parents. Testing was only performed on two of the newborns in the family. A novel homozygous nonsense c.2767C>T p.(Arg932*) variant in the exon 19 of the CACNA1A gene (NM_001127221.1). Segregation analysis showed that both parents were heterozygous carriers and they were diagnosed with EA2.; to: Four infants, all presenting with hypotonia, mild facial dysmorphic features, encephalopathy, and seizures, born
to consanguineous parents. Testing was only performed on two of the newborns in the family. A novel homozygous nonsense c.2767C>T p.(Arg932*) variant in the exon 19 of the CACNA1A gene (NM_001127221.1). Segregation analysis showed that both parents were heterozygous carriers and they were diagnosed with EA2.

Well established association between mono-allelic variants and a number of phenotypes including episodic ataxia.
Brain channelopathy v1.70 CACNA1A Zornitza Stark reviewed gene: CACNA1A: Rating: RED; Mode of pathogenicity: None; Publications: 34267336; Phenotypes: Hypotonia, encephalopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital myopathy v2.68 MLIP Zornitza Stark gene: MLIP was added
gene: MLIP was added to Congenital myopathy. Sources: Literature
Mode of inheritance for gene: MLIP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MLIP were set to 34581780
Phenotypes for gene: MLIP were set to MLIP-related myopathy with rhabdomyolysis
Review for gene: MLIP was set to GREEN
Added comment: PMID: 34581780: 7 individuals with 6 families with truncating (one splice that also resulted in a frameshift variant) biallelic variants (used NM_1281746).

In 3 patients patients’ skeletal muscle, these variants were shown to cause reduction overall RNA expression levels of the predominant MLIP isoform.

Patients presented with a consistent phenotype characterized by mild muscle weakness, exercise-induced muscle pain, variable susceptibility to episodes of rhabdomyolysis, and persistent basal elevated serum creatine kinase levels.
Sources: Literature
Congenital disorders of glycosylation v2.78 STT3A Zornitza Stark changed review comment from: Three families reported to date.; to: Bi-allelic variants: Three families reported to date.
Congenital disorders of glycosylation v2.78 STT3A Zornitza Stark edited their review of gene: STT3A: Added comment: New MOI

PMID: 34653363 - 16 patients from 9 families with new AD mode of inheritance (both de novo and inherited). All variants were missense within/around acritical active/catalytic sites. Patients aged 3-55yo, with children noted to be "healthy" until reaching young adulthood
Clinical features include dysmorphic features, macrocephaly (6/16), mild-moderate ID/DD (10/16), short stature (8/16), skeletal abnormalities (10/16), muscle cramps (7/16).
Functional studies verifies AR disease is caused by LOF variants, whereas the AD variants cause DN proven by cotransfection in WT yeast resulting in impaired glycosylation (protein levels unchanged).; Changed publications to: 23842455, 30701557, 28424003, 34653363; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mitochondrial disorders v2.63 KIAA0391 Zornitza Stark gene: KIAA0391 was added
gene: KIAA0391 was added to Mitochondrial disorders. Sources: Literature
Mode of inheritance for gene: KIAA0391 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIAA0391 were set to 34715011
Phenotypes for gene: KIAA0391 were set to Hearing loss, intellectual disability
Review for gene: KIAA0391 was set to GREEN
gene: KIAA0391 was marked as current diagnostic
Added comment: Four unrelated families with multisystem disease associated with bi-allelic variants in PRORP, HGNC approved name is KIAA0391. Affected individuals presented with variable phenotypes comprising sensorineural hearing loss, primary ovarian insufficiency, developmental delay, and brain white matter changes.

-1 consanguineous family with homozygous missense in 3 affected sisters, het parents unaffected. Siblings had profound bilateral SNHL in infancy. In teens developed primary amenorrhea/Perrault syndrome, and hypergonadotropic hypogonadism.
-1 unrelated male with compound het missense, each inherited from an unaffected parent. Hearing loss noted at 3, diagnosed at 5.
-1 unrelated male compound het for a missense and a frameshift. appendicular hypertonia in infancy, mild dysmorphism. Severe global dev delay at 20 months. Normal hearing at 18 months, but at 3 years had bilateral SNHL.
-an affected mother and her 2 affected children (son and daughter), homozygous for a missense. Father is heterozygous and unaffected. Son has psychotic disorder, autistic traits. Sister had intrauterine growth retardation, global developmental delay, and seizures in the first years of life. Mother presented with retrobulbar optic neuritis and tonic pupil at 39 years of age, then with asthenia, myalgias, memory loss, and frequent headaches.
Sources: Literature
Congenital disorders of glycosylation v2.78 OSTC Zornitza Stark gene: OSTC was added
gene: OSTC was added to Congenital disorders of glycosylation. Sources: Literature
Mode of inheritance for gene: OSTC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OSTC were set to 32267060
Phenotypes for gene: OSTC were set to Oligosaccharyltransferase complex-congenital disorders of glycosylation
Review for gene: OSTC was set to RED
Added comment: A patient with microcephaly, dysmorphic facies, congenital heart defect, focal epilepsy, infantile spasms, skeletal dysplasia, and a type 1 serum transferrin isoelectrofocusing due to a novel CDG caused by a homozygous variant in the oligosaccharyltransferase complex noncatalytic subunit (OSTC) gene involved in glycosylation and confirmed by serum transferrin electrophoresis.
Patient was homozygous for a canonical splice variant (c.431 + 1G > A), mRNA from patient's fibroblast showed mRNA transcript reduced 80-90%/aberrant splicing - predicting NMD.
GnomAD - 10 hets, 0 hom
Sources: Literature
Early onset or syndromic epilepsy v2.477 KCNC2 Zornitza Stark gene: KCNC2 was added
gene: KCNC2 was added to Genetic epilepsy syndromes. Sources: Literature
Mode of inheritance for gene: KCNC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNC2 were set to 32392612; 31972370
Phenotypes for gene: KCNC2 were set to epileptic encephalopathy; spastic tetraplegia; opisthotonus attacks; intellectual disability; West syndrome
Review for gene: KCNC2 was set to AMBER
Added comment: PMID: 31972370. De novo missense variant (p.Val471Leu) identified in a child with early severe developmental and epileptic encephalopathy, spastic tetraplegia, opisthotonos attacks.

PMID: 32392612. De novo missense variant (p.Asp167Tyr) identified in a neurofibromatosis type 1 related West syndrome patient. Functional analysis showed a significant reduction of the mean potassium current and a shift in the voltage dependence of steady-state activation. Maternally inherited NF1 variant (p.T1951Nfs*5) also identified, the mother was "clinically unremarkable".
Sources: Literature
Intellectual disability v3.1478 NSRP1 Zornitza Stark gene: NSRP1 was added
gene: NSRP1 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: NSRP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NSRP1 were set to 34385670
Phenotypes for gene: NSRP1 were set to Epilepsy; Cerebral palsy; microcephaly; Intellectual disability
Review for gene: NSRP1 was set to GREEN
gene: NSRP1 was marked as current diagnostic
Added comment: Novel gene regulating splicing. Biallelic LoF pathogenic variants reported in 6 individuals from 3 unrelated families associated with a phenotype characterized by developmental delay, epilepsy, microcephaly, and spastic cerebral palsy.
Sources: Literature
Intellectual disability v3.1478 SPRED2 Zornitza Stark gene: SPRED2 was added
gene: SPRED2 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: SPRED2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPRED2 were set to 34626534
Phenotypes for gene: SPRED2 were set to developmental delay; intellectual disability; cardiac defects; short stature; skeletal anomalies; a typical facial gestalt
Review for gene: SPRED2 was set to GREEN
gene: SPRED2 was marked as current diagnostic
Added comment: PMID: 34626534
Homozygosity for three different variants c.187C>T (p.Arg63∗), c.299T>C (p.Leu100Pro), and c.1142_1143delTT (p.Leu381Hisfs∗95) were identified in four subjects from three families. All variants severely affected protein stability, causing accelerated degradation, and variably perturbed SPRED2 functional behaviour. The clinical phenotype of the four affected individuals included developmental delay, intellectual disability, cardiac defects, short stature, skeletal anomalies, and a typical facial gestalt as major features, without the occurrence of the distinctive skin signs characterizing Legius syndrome.
Sources: Literature
Intellectual disability v3.1478 SPATA5L1 Zornitza Stark gene: SPATA5L1 was added
gene: SPATA5L1 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: SPATA5L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPATA5L1 were set to 34626583
Phenotypes for gene: SPATA5L1 were set to Neurodevelopmental disorder with hearing loss and spasticity, MIM# 619616
Review for gene: SPATA5L1 was set to GREEN
gene: SPATA5L1 was marked as current diagnostic
Added comment: 47 individuals from 26 unrelated families from various ethnicities with biallelic variants reported. Phenotypes include ID, hearing impairment, movement disorder, abnormal MRI, hypotonia, visual impairment, epilepsy, and microcephaly.

~53% of patients had ID.
Sources: Literature
Mitochondrial disorders v2.63 TARS2 Zornitza Stark reviewed gene: TARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33153448, 24827421, 34508595; Phenotypes: Combined oxidative phosphorylation deficiency 21 - 615918; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.1478 OGDHL Zornitza Stark gene: OGDHL was added
gene: OGDHL was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: OGDHL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OGDHL were set to 34800363
Phenotypes for gene: OGDHL were set to Neurodevelopmental disorder featuring epilepsy, hearing loss and visual impairment
Review for gene: OGDHL was set to GREEN
Added comment: Nine individuals from eight unrelated families carrying bi-allelic variants in OGDHL with a range of neurological and neurodevelopmental phenotypes including epilepsy, hearing
loss, visual impairment, gait ataxia, microcephaly, and hypoplastic corpus callosum.

Homozygous and compound heterozygous variants reported. Variant types reported include missense, PTCs and a synonymous variant that was shown to affect splicing.

Functional studies with a CRISPR-Cas9-mediated tissue knockout with cDNA rescue system showed that the missense variants result in loss-of-function.
Sources: Literature
Mitochondrial disorders v2.63 OGDH Zornitza Stark reviewed gene: OGDH: Rating: AMBER; Mode of pathogenicity: None; Publications: 32383294; Phenotypes: Developmental delay, ataxia, seizure, raised lactate; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Undiagnosed metabolic disorders v1.501 HIBADH Zornitza Stark gene: HIBADH was added
gene: HIBADH was added to Undiagnosed metabolic disorders. Sources: Literature
Mode of inheritance for gene: HIBADH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HIBADH were set to 34176136
Phenotypes for gene: HIBADH were set to organic aciduria
Review for gene: HIBADH was set to RED
Added comment: Single family reported with two siblings presenting with 3-Hydroxyisobutyric aciduria. Male sib with neurodevelopmental symptoms, female sibling asymptomatic. No functional studies
Sources: Literature
Severe microcephaly v2.274 ARPC4 Zornitza Stark gene: ARPC4 was added
gene: ARPC4 was added to Severe microcephaly. Sources: Literature
Mode of inheritance for gene: ARPC4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARPC4 were set to DOI:https://doi.org/10.1016/j.xhgg.2021.100072
Phenotypes for gene: ARPC4 were set to Microcephaly; mild motor delays; significant speech impairment
Review for gene: ARPC4 was set to GREEN
Added comment: 7 affected individuals from 6 families (gonadal mosaicism was confirmed in the mother of the 2 affected siblings) with a recurrent missense variant (NM_005718.4:c.472C>T; p.R158C). 6/7 affected individuals had microcephaly. The variant was associated with a decreased amount of F-actin in cells from two affected individuals.
Sources: Literature
Adult onset leukodystrophy v1.36 LAMB1 Zornitza Stark changed review comment from: Mono-allelic LAMB1 variants reported in 5 families with cerebral small vessel disease. 4 are truncating frameshifts (and 2 of the families have the same frameshift), 1 is a canonical splice. All families had adult onset of symptoms ranging from 20-63yo. All has white matter hyper intensity on imaging.; to: New MOI

Mono-allelic LAMB1 variants reported in 5 families with cerebral small vessel disease. 4 are truncating frameshifts (and 2 of the families have the same frameshift), 1 is a canonical splice. All families had adult onset of symptoms ranging from 20-63yo. All has white matter hyper intensity on imaging.
Adult onset leukodystrophy v1.36 LAMB1 Zornitza Stark edited their review of gene: LAMB1: Added comment: Mono-allelic LAMB1 variants reported in 5 families with cerebral small vessel disease. 4 are truncating frameshifts (and 2 of the families have the same frameshift), 1 is a canonical splice. All families had adult onset of symptoms ranging from 20-63yo. All has white matter hyper intensity on imaging.; Changed rating: GREEN; Changed publications to: 32548278, 34606115; Changed phenotypes to: Adult-onset leukodystrophy; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v3.1478 FOXR1 Zornitza Stark gene: FOXR1 was added
gene: FOXR1 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: FOXR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FOXR1 were set to 34723967
Phenotypes for gene: FOXR1 were set to Postnatal microcephaly, progressive brain atrophy and global developmental delay
Review for gene: FOXR1 was set to AMBER
Added comment: 1 patient described with a de novo missense variant. Phenotypes include: postnatal microcephaly, progressive brain atrophy, skeletal abnormalities, brain abnormalities, ophthalmic abnormalities, neuromuscular abnormalities, and dysmorphic features. A variant in ATP1A3 was considered to have contributed to the final phenotype.

In vitro functional evidence is supportive of pathogenicity (variant causes protein instability and abnormal nuclear aggregation).

A mouse knockout has comparable phenotypes, and a severe survival deficit.

Rated amber (1 patient, functional evidence, mouse model).
Sources: Literature
Possible mitochondrial disorder - nuclear genes v1.60 SLIRP Zornitza Stark gene: SLIRP was added
gene: SLIRP was added to Possible mitochondrial disorder - nuclear genes. Sources: Literature
Mode of inheritance for gene: SLIRP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLIRP were set to 34426662
Phenotypes for gene: SLIRP were set to Mitochondrial encephalomyopathy with complex I and IV deficiency
Review for gene: SLIRP was set to RED
Added comment: Single Dutch non-consanguineous patient having mitochondrial encephalomyopathy with complex I and complex IV deficiency, whole exome sequencing revealed two compound heterozygous variants (NM_031210.5:c.248_252del; NP_112487.1:p.(Ile83Argfs*10) and NC_000014.8:g.78177003 A > G; NM_031210.5:c.98-178 A > G) in SLIRP. Report SLIRP variants as a novel cause of mitochondrial encephalomyopathy with OXPHOS deficiency
Sources: Literature
Possible mitochondrial disorder - nuclear genes v1.60 ATP5A1 Zornitza Stark reviewed gene: ATP5A1: Rating: AMBER; Mode of pathogenicity: None; Publications: 34483339; Phenotypes: feeding intolerance, failure to thrive, hyperammonaemia, lactic acidaemia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.819 TAB2 Zornitza Stark reviewed gene: TAB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34456334; Phenotypes: Mitral valve disease, cardiomyopathy, short stature and hypermobility, Rasopathy-like; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v2.498 CARD10 Zornitza Stark gene: CARD10 was added
gene: CARD10 was added to Primary immunodeficiency. Sources: Literature
Mode of inheritance for gene: CARD10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CARD10 were set to 32238915
Phenotypes for gene: CARD10 were set to Immunodeficiency 89 and autoimmunity, MIM# 619632
Review for gene: CARD10 was set to RED
Added comment: A pair of siblings reported with adult onset of recurrent infections, allergies, microcytic anaemia, and Crohn disease. Homozygous missense variant.
Sources: Literature
Primary ovarian insufficiency v1.60 POLR3H Zornitza Stark gene: POLR3H was added
gene: POLR3H was added to Primary ovarian insufficiency. Sources: Expert Review
Mode of inheritance for gene: POLR3H was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR3H were set to 34794894; 30830215
Phenotypes for gene: POLR3H were set to Primary ovarian insufficiency
Review for gene: POLR3H was set to AMBER
Added comment: A homozygous missense variant (p.Asp50Gly) was identified homozygous in 2 unrelated families. A mull mouse model was embryonic lethal, but a mouse model homozygous for the missense were viable and showed delayed pubertal development, characterised by late first oestrus or preputial separation.
Sources: Expert Review
Primary ovarian insufficiency v1.60 POLR2C Zornitza Stark gene: POLR2C was added
gene: POLR2C was added to Primary ovarian insufficiency. Sources: Literature
Mode of inheritance for gene: POLR2C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POLR2C were set to 34794894; 29367954
Phenotypes for gene: POLR2C were set to Primary ovarian insufficiency
Review for gene: POLR2C was set to AMBER
Added comment: One family with POI segregating a nonsense variant (p.Lys152Ter) and a case with sporadic POI with a splice region variant (c.206-3C>T). Knockdown of the gene in an embryonic carcinoma cell line resulted in decreased protein production and impaired cell proliferation.
Two missense in premature ovarian failure cases submitted to ClinVar by Shandong Provincial Hospital Affiliated to Shandong University (SCV001877131.1, SCV001877153.1).
Sources: Literature
Primary ovarian insufficiency v1.60 KHDRBS1 Zornitza Stark gene: KHDRBS1 was added
gene: KHDRBS1 was added to Primary ovarian insufficiency. Sources: Literature
Mode of inheritance for gene: KHDRBS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KHDRBS1 were set to 34794894; 29808484; 28938739; 20881015
Phenotypes for gene: KHDRBS1 were set to Premature ovarian failure
Review for gene: KHDRBS1 was set to GREEN
gene: KHDRBS1 was marked as current diagnostic
Added comment: 4 individuals in 3 unrelated families and a supporting mouse model
PMID: 28938739 - missense (c.460A > G, p.M154V) identified in a Chinese mother and daughter with POI, and another missense (c.263C > T, p.P88L) identified in an idiopathic POI case.
SCV001364312.1 - case with POI and missense (p.Pro421Leu) submitted by an Italian institute (ClinVar ID: 929733)
PMID: 29808484 - missense (p.Pro296Leu) identified in a POI case, which also has a heterozygous missense in FGFR2. There are 12 hets with Pro296Leu in gnomAD v2.1. This case is not included in the final case count.
PMID: 20881015 - supporting null mouse model. Female mice were subfertile.
Sources: Literature
Retinal disorders v2.236 HKDC1 Zornitza Stark gene: HKDC1 was added
gene: HKDC1 was added to Retinal disorders. Sources: Literature
Mode of inheritance for gene: HKDC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HKDC1 were set to 30085091
Phenotypes for gene: HKDC1 were set to Retinitis pigmentosa 92, MIM# 619614
Review for gene: HKDC1 was set to RED
Added comment: Two unrelated Chinese men reported with relatively late-onset RP, and same homozygous missense variant.
Sources: Literature
Congenital hyperinsulinism v2.8 NSD1 Ivone Leong Tag Q4_21_rating tag was added to gene: NSD1.
Congenital hyperinsulinism v2.8 NSD1 Ivone Leong Classified gene: NSD1 as Amber List (moderate evidence)
Congenital hyperinsulinism v2.8 NSD1 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in OMIM and Gene2Phenotype (Definitive). There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Congenital hyperinsulinism v2.8 NSD1 Ivone Leong Gene: nsd1 has been classified as Amber List (Moderate Evidence).
Congenital hyperinsulinism v2.7 GPC3 Ivone Leong Tag Q4_21_phenotype tag was added to gene: GPC3.
Congenital hyperinsulinism v2.7 AKT2 Ivone Leong Tag Q4_21_phenotype tag was added to gene: AKT2.
Congenital hyperinsulinism v2.7 AKT2 Ivone Leong Tag Q4_21_expert_review tag was added to gene: AKT2.
Congenital hyperinsulinism v2.7 GPC3 Ivone Leong Tag Q4_21_expert_review tag was added to gene: GPC3.
Congenital hyperinsulinism v2.7 UCP2 Ivone Leong Tag watchlist tag was added to gene: UCP2.
Congenital hyperinsulinism v2.7 UCP2 Ivone Leong Classified gene: UCP2 as Amber List (moderate evidence)
Congenital hyperinsulinism v2.7 UCP2 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in OMIM but not Gene2Phenotype. There is currently not enough evidence to support a gene-disease association. This gene has been given an Amber rating.
Congenital hyperinsulinism v2.7 UCP2 Ivone Leong Gene: ucp2 has been classified as Amber List (Moderate Evidence).
Congenital hyperinsulinism v2.6 UCP2 Ivone Leong Phenotypes for gene: UCP2 were changed from Hyperinsulinism to Hyperinsulinism, MONDO:0002177
Pituitary hormone deficiency v2.10 RNPC3 Ivone Leong Classified gene: RNPC3 as Amber List (moderate evidence)
Pituitary hormone deficiency v2.10 RNPC3 Ivone Leong Gene: rnpc3 has been classified as Amber List (Moderate Evidence).
Pituitary hormone deficiency v2.9 RNPC3 Ivone Leong Tag watchlist tag was added to gene: RNPC3.
Pituitary hormone deficiency v2.9 RNPC3 Ivone Leong edited their review of gene: RNPC3: Added comment: PMID:33650182 a third case reported with growth failure, second case with ID and growth failure. In this case the patient has GH and PRL deficiencies, as well as undetectably low IGF1 levels. This is the second case where there are >2 pituitary hormone deficiency. Thefore this gene should be promoted from Red to Amber.; Changed rating: AMBER; Changed publications to: 33650182
Intellectual disability v3.1478 RNPC3 Ivone Leong changed review comment from: PMID:33650182 a third case reported with growth failure and ID. This is the second case where a patient with a variant in RNPC3 has ID. Therefore the Amber rating.; to: PMID:33650182 a third case reported with growth failure. This is the second case where a patient with a variant in RNPC3 has ID. Therefore the Amber rating.
Intellectual disability v3.1478 RNPC3 Ivone Leong changed review comment from: PMID:33650182 a third case reported with growth failure and ID.; to: PMID:33650182 a third case reported with growth failure and ID. This is the second case where a patient with a variant in RNPC3 has ID. Therefore the Amber rating.
Intellectual disability v3.1478 RNPC3 Ivone Leong changed review comment from: Comment on list classification: Promoted from Red to Amber based on my other review.; to: Comment on list classification: Promoted from Red to Amber based on my other review.
Pituitary hormone deficiency v2.9 RNPC3 Ivone Leong Phenotypes for gene: RNPC3 were changed from isolated growth hormone deficiency; ?Growth hormone deficiency, isolated, type V, 618160 to Pituitary hormone deficiency, combined or isolated, 7, OMIM:618160
Pituitary hormone deficiency v2.8 RNPC3 Ivone Leong Publications for gene: RNPC3 were set to 24480542; 29866761; 32462814
Intellectual disability v3.1478 RNPC3 Ivone Leong Tag watchlist tag was added to gene: RNPC3.
IUGR and IGF abnormalities v1.49 RNPC3 Ivone Leong Classified gene: RNPC3 as Green List (high evidence)
IUGR and IGF abnormalities v1.49 RNPC3 Ivone Leong Added comment: Comment on list classification: Promoted from Amber to Green. PMID:33650182 a third case reported with growth failure and ID. There is now enough evidence to support a gene-disease association.
IUGR and IGF abnormalities v1.49 RNPC3 Ivone Leong Gene: rnpc3 has been classified as Green List (High Evidence).
IUGR and IGF abnormalities v1.48 RNPC3 Ivone Leong Publications for gene: RNPC3 were set to 24480542; 29866761; 32462814
IUGR and IGF abnormalities v1.47 RNPC3 Ivone Leong Phenotypes for gene: RNPC3 were changed from isolated growth hormone deficiency; ?Growth hormone deficiency, isolated, type V, 618160 to Pituitary hormone deficiency, combined or isolated, 7, OMIM:618160
Intellectual disability v3.1478 RNPC3 Ivone Leong Publications for gene: RNPC3 were set to 24480542; 29866761; 32462814
Intellectual disability v3.1477 RNPC3 Ivone Leong Phenotypes for gene: RNPC3 were changed from isolated growth hormone deficiency; ?Growth hormone deficiency, isolated, type V, 618160; developmental delay/intellectual deficiency and delayed puberty to Pituitary hormone deficiency, combined or isolated, 7, OMIM:618160
Intellectual disability v3.1476 RNPC3 Ivone Leong Classified gene: RNPC3 as Amber List (moderate evidence)
Intellectual disability v3.1476 RNPC3 Ivone Leong Added comment: Comment on list classification: Promoted from Red to Amber based on my other review.
Intellectual disability v3.1476 RNPC3 Ivone Leong Gene: rnpc3 has been classified as Amber List (Moderate Evidence).
Intellectual disability v3.1475 RNPC3 Ivone Leong edited their review of gene: RNPC3: Added comment: PMID:33650182 a third case reported with growth failure and ID.; Changed rating: AMBER; Changed publications to: 24480542, 29866761, 32462814, 33650182
Early onset dystonia v1.99 ACTB Eldar Dedic changed review comment from: Freitas, et al. (2020, PMID 31970217) presented 52 years of age Brazilian female case with dystonia (onset at age of 25 years) who had additional clinical features (but without facial dysmorphism and brain abnormalities). Whole-exome-sequencing showed the presence of ACTB c.547C>T (p.Arg183Trp) variant. This variant was absent from gnomAD v2.1.1 as of December 2021.

Skogseid, et al. (2018, PMID 29788902) presented 23 years old female case with dystonia (age at onset 13 years), mild dysmorphic facial traits and additional clinical features (but with grossly maintained brain structure). Whole-exome-sequencing revealed heterozygous ACTB c.547C>T (p.Arg183Trp) variant. The case was negative for the aCGH analysis.

Zech, et al. (2017, PMID 28849312) presented 9 unrelated cases with combined and/or complex dystonia (8 of European and 1 of Asian origin). Whole-exome-sequencing revealed de novo ACTB c.547C>T (p.Arg183Trp) variant in 39-years-old Czech male case with complex dystonia (age of onset at 24 years) who had additional clinical features (but with normal brain MRI). The variant absence in parents has been confirmed through Sanger sequencing.

Eggink, et al. (2017, PMID 27862284) presented a family with dystonia. Whole-exome-sequencing revealed ACTB c.547C>T (p.Arg183Trp) variant in 2 family members: 22 years old female with dystonia (age of onset at 19 years) who in addition to other clinical features showed high-arched eyebrows (but with normal brain MRI results); her 49 years old mother with dystonia (who at age 16 experienced hands trembling, at age 21 she had writer’s cramp diagnosed) and additional clinical features.

Cuvertino, et al. (2017, PMID 29220674) analyzed data of more than 15,000 suspected genetic development disorder individuals, 26 cases with 7p22.1 deletions and 4,293 trios from the Deciphering Developmental Disorders study. The ACTB c.1097dupG (p.Ser368Leufs*13) variant has been found de novo in 12 years old heterozygous male case (of United Kingdom origin; Table S1) who had dystonia (as well as additional clinical features; Table 1). This variant was absent from gnomAD v2.1.1 as of December 2021.
(Please note that ACTB c.1097dupG (p.Ser368Leufs*13) results in extension of protein)

Hundt, et al. (2014, PMID 25255767) presented in vitro functional study on Sf9 cells. The results showed that ACTB c.547C>T (p.Arg183Trp) variant resulted in 3 times higher inhibition of DNase I-mediated nucleic acid cleavage (p < 0.0001; Fig.2A), unchanged thermal stability (Fig. 2B), nucleotide exchange from actin monomer was 2.4 times slower (p = 0.0113; Fig.3), 1.9 times faster half-time polymerization (p = 0.0006; Fig. 4A), 1.7 times higher ATP turnover (Fig. 4B), significantly reduced half-time of the depolymerization (Fig. 4C), close to normal binding to the profilin II (Fig. 5A), 4 times lower ability to activate ATPase of nonmuscle myosin-2A isoform (Fig. 6), in comparison to the wild-type. The authors also carried out the computational analysis and showed that this variant impaired the opening of the nucleotide cleft (Fig. 7C, Fig. 8B).; to: Freitas, et al. (2020, PMID: 31970217) presented 52 years of age Brazilian female case with dystonia (onset at age of 25 years) who had additional clinical features (but without facial dysmorphism and brain abnormalities). Whole-exome-sequencing showed the presence of ACTB c.547C>T (p.Arg183Trp) variant. This variant was absent from gnomAD v2.1.1 as of December 2021.

Skogseid, et al. (2018, PMID: 29788902) presented 23 years old female case with dystonia (age at onset 13 years), mild dysmorphic facial traits and additional clinical features (but with grossly maintained brain structure). Whole-exome-sequencing revealed heterozygous ACTB c.547C>T (p.Arg183Trp) variant. The case was negative for the aCGH analysis.

Zech, et al. (2017, PMID: 28849312) presented 9 unrelated cases with combined and/or complex dystonia (8 of European and 1 of Asian origin). Whole-exome-sequencing revealed de novo ACTB c.547C>T (p.Arg183Trp) variant in 39-years-old Czech male case with complex dystonia (age of onset at 24 years) who had additional clinical features (but with normal brain MRI). The variant absence in parents has been confirmed through Sanger sequencing.

Eggink, et al. (2017, PMID: 27862284) presented a family with dystonia. Whole-exome-sequencing revealed ACTB c.547C>T (p.Arg183Trp) variant in 2 family members: 22 years old female with dystonia (age of onset at 19 years) who in addition to other clinical features showed high-arched eyebrows (but with normal brain MRI results); her 49 years old mother with dystonia (who at age 16 experienced hands trembling, at age 21 she had writer’s cramp diagnosed) and additional clinical features.

Cuvertino, et al. (2017, PMID: 29220674) analyzed data of more than 15,000 suspected genetic development disorder individuals, 26 cases with 7p22.1 deletions and 4,293 trios from the Deciphering Developmental Disorders study. The ACTB c.1097dupG (p.Ser368Leufs*13) variant has been found de novo in 12 years old heterozygous male case (of United Kingdom origin; Table S1) who had dystonia (as well as additional clinical features; Table 1). This variant was absent from gnomAD v2.1.1 as of December 2021.
(Please note that ACTB c.1097dupG (p.Ser368Leufs*13) results in extension of protein)

Hundt, et al. (2014, PMID: 25255767) presented in vitro functional study on Sf9 cells. The results showed that ACTB c.547C>T (p.Arg183Trp) variant resulted in 3 times higher inhibition of DNase I-mediated nucleic acid cleavage (p < 0.0001; Fig.2A), unchanged thermal stability (Fig. 2B), nucleotide exchange from actin monomer was 2.4 times slower (p = 0.0113; Fig.3), 1.9 times faster half-time polymerization (p = 0.0006; Fig. 4A), 1.7 times higher ATP turnover (Fig. 4B), significantly reduced half-time of the depolymerization (Fig. 4C), close to normal binding to the profilin II (Fig. 5A), 4 times lower ability to activate ATPase of nonmuscle myosin-2A isoform (Fig. 6), in comparison to the wild-type. The authors also carried out the computational analysis and showed that this variant impaired the opening of the nucleotide cleft (Fig. 7C, Fig. 8B).
Early onset dystonia v1.99 ACTB Eldar Dedic reviewed gene: ACTB: Rating: GREEN; Mode of pathogenicity: Other; Publications: 31970217, 29788902, 28849312, 27862284, 29220674, 25255767; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset dystonia v1.99 ACTB Eldar Dedic Deleted their review
Early onset dystonia v1.99 ACTB Eldar Dedic reviewed gene: ACTB: Rating: GREEN; Mode of pathogenicity: Other; Publications: ; Phenotypes: 31970217, 29788902, 28849312, 27862284, 29220674, 25255767; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia with onset in adulthood v2.133 RFC1 Dmitrijs Rots changed review comment from: Only STR in this gene is associated with CANVAS / ataxia. Addition of this gene to the panel will result only in unnecessary load of RFC1 SNV/indel/CNV analysis, which are not related to human disorder.; to: Only STR in this gene is associated with CANVAS / ataxia. Addition of this gene to the panel will result only in unnecessary load of RFC1 SNV/indel/CNV analysis, which are not related to human disorder.
Additionallly, RFC1 repeat expansion, is commonly associated with sensory neuropathy (at the moment of presentation usually without clinically prominent ataxia) ,so the STR should be added to the neuropathy panel as well, not just ataxia (PMID: 33969391).
Hereditary ataxia with onset in adulthood v2.133 RFC1 Dmitrijs Rots reviewed gene: RFC1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.1475 ANK3 Dmitrijs Rots reviewed gene: ANK3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34218362; Phenotypes: Intellectual disability; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary ataxia with onset in adulthood v2.133 RFC1 Eleanor Williams Classified gene: RFC1 as Amber List (moderate evidence)
Hereditary ataxia with onset in adulthood v2.133 RFC1 Eleanor Williams Added comment: Comment on list classification: Promoting this gene from grey to amber, but noting that it is repeat expansions within an intron that is associated with the CANVAS phenotype, not SNVs within the protein coding region. Added to the list of STRs to be added.
Hereditary ataxia with onset in adulthood v2.133 RFC1 Eleanor Williams Gene: rfc1 has been classified as Amber List (Moderate Evidence).
Hereditary ataxia with onset in adulthood v2.132 RFC1 Eleanor Williams Phenotypes for gene: RFC1 were changed from Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome OMIM 614575 to Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome, OMIM:614575; cerebellar ataxia, neuropathy, and vestibular areflexia syndrome, MONDO:0013809; chronic idiopathic axonal polyneuropathy; chronic polyneuropathy, MONDO:0003335
Hereditary ataxia with onset in adulthood v2.131 RFC1 Eleanor Williams Publications for gene: RFC1 were set to 30926972
Hereditary ataxia with onset in adulthood v2.130 RFC1 Eleanor Williams Tag STR tag was added to gene: RFC1.
Hereditary ataxia with onset in adulthood v2.130 RFC1 Eleanor Williams changed review comment from: The gene is associated with Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) #614575 (AR) with two repeat expansions cited as the allelic variants.

PMID: 30926972 - Cortese et al 2019 - found a recessive intronic AAGGG repeat expansion in the RFC1 gene as a cause of familial CANVAS in 11 families. 4 SNPs around RFC1 were shared by all individuals except in family 5, suggesting a founder haplotype. They found an additional 33 sporadic cases carrying the recessive AAGGG repeat expansion in a cohort of 150 patients diagnosed with sporadic late-onset ataxia (22%). They also note that all sporadic cases with the repeat expansion, except for one individual, shared the same haplotype as familial CANVAS cases. Although the expansion size varied across different families, ranging from around 400 to 2000 repeats, in the majority of cases approximately 1000 repeats were observed. In 304 healthy controls, 4/608 chromosomes (0.7%) chromosomes carried an AAGGG expansion in the heterozygous state. 3 other conformations were observed: (AAAAG)11 (75.5%); (AAAAG)exp(13.0%); and (AAAGG)exp (7.9%). They did not observe a reduced level of RFC1 expression at either the transcript or the protein level in CANVAS patients.

PMID: 31824583 - Akçimen et al 2019 - looked at RFC1 repeat expansions in cohort of Brazilian cases and two cohorts of Canadian cases. 1 Brazilian and 1 Canadian case were found to carry the causative biallelic AAGGG repeat expansion. Two novel repeat sequences were found in the heterozygous state; AAGAG and AGAGG.

PMID: 32851396 - Beecroft et al 2020 - describe a (AAAGG)10-25(AAGGG)exp found in New Zealand Māori and Cook Island Māori individuals which was the cause of CANVAS in all patients. Patients in 2 families also had small number of repeats of the benign variant allele (AAAGG)4-6 at the distal end of the RFC1 pathogenic expansion. The 4 patients with WGS data were found to share the same core haplotype as described in European populations in Cortese et al 2019, plus an additional region.

PMID: 32582864 - Syriani et al 2020 - 29 patients from North America were identified with biallelic repeat expansions in RFC1 (AAGGG) (3.2% of total). Of these 29 patients, 8 (28%) had a clinical diagnosis of cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS), 14 had cerebellar ataxia with neuropathy (48%), 4 had pure cerebellar ataxia (14%).

PMID: 33969391 - Curro et al 2021 - retrospectively identified 225 patients diagnosed with chronic idiopathic axonal polyneuropathy (125 sensory neuropathy, 100 sensory-motor neuropathy). Patients previously diagnosed with CANVAS or with a family history of CANVAS were not included. 43 patients (34%) with sensory neuropathy had biallelic AAGGG repeat expansions in RFC1and in none with sensory-motor neuropathy.; to: The gene is associated with Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) #614575 (AR) with two repeat expansions cited as the allelic variants.

There is data to suggest a common haplotype between most cases but this appears to be quite ancient (25000 yo) and so the cases from individuals from different countries can probably be counted as being unrelated. The mechanism of action of this intronic repeat expansion is not yet known.

= AAGGG repeat expansion =

PMID: 30926972 - Cortese et al 2019 - found a recessive intronic AAGGG repeat expansion in the RFC1 gene as a cause of familial CANVAS in 11 families. 4 SNPs around RFC1 were shared by all individuals except in family 5, suggesting a founder haplotype. They found an additional 33 sporadic cases carrying the recessive AAGGG repeat expansion in a cohort of 150 patients diagnosed with sporadic late-onset ataxia (22%). They also note that all sporadic cases with the repeat expansion, except for one individual, shared the same haplotype as familial CANVAS cases. Although the expansion size varied across different families, ranging from around 400 to 2000 repeats, in the majority of cases approximately 1000 repeats were observed. In 304 healthy controls, 4/608 chromosomes (0.7%) chromosomes carried an AAGGG expansion in the heterozygous state. 3 other conformations were observed: (AAAAG)11 (75.5%); (AAAAG)exp(13.0%); and (AAAGG)exp (7.9%). They did not observe a reduced level of RFC1 expression at either the transcript or the protein level in CANVAS patients.

PMID: 31824583 - Akçimen et al 2019 - looked at RFC1 repeat expansions in cohort of Brazilian cases and two cohorts of Canadian cases. 1 Brazilian and 1 Canadian case were found to carry the causative biallelic AAGGG repeat expansion. Two novel repeat sequences were found in the heterozygous state; AAGAG and AGAGG.

PMID: 31230722 - Rafehi et al 2019 - bioinformatics paper looking at using Expansion Hunter de novo on WGS data but also reports RFC1 (AAGGG)exp in 18/22 CANVAS families. Also states that the core ancestral haplotype is estimated to have arisen in Europe more than twenty-five thousand years ago.

PMID: 32851396 - Beecroft et al 2020 - describe a (AAAGG)10-25(AAGGG)exp found in New Zealand Māori and Cook Island Māori individuals which was the cause of CANVAS in all patients. Patients in 2 families also had small number of repeats of the benign variant allele (AAAGG)4-6 at the distal end of the RFC1 pathogenic expansion. The 4 patients with WGS data were found to share the same core haplotype as described in European populations in Cortese et al 2019, plus an additional region.

PMID: 32582864 - Syriani et al 2020 - 29 patients from North America were identified with biallelic repeat expansions in RFC1 (AAGGG) (3.2% of total). Of these 29 patients, 8 (28%) had a clinical diagnosis of cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS), 14 had cerebellar ataxia with neuropathy (48%), 4 had pure cerebellar ataxia (14%).

PMID: 32694621 - Tsuchiya et al 2020 - found intronic (AAGGG) repeat expansions in RFC1 in 3 (12%) of the familial Japanese patients with CANVAS and 1 (8.5%) of the sporadic ones.

PMID: 33969391 - Curro et al 2021 - retrospectively identified 225 patients diagnosed with chronic idiopathic axonal polyneuropathy (125 sensory neuropathy, 100 sensory-motor neuropathy). Patients previously diagnosed with CANVAS or with a family history of CANVAS were not included. 43 patients (34%) with sensory neuropathy had biallelic AAGGG repeat expansions in RFC1and in none with sensory-motor neuropathy.

= ACAGG repeat expansion =

PMID: 33103729 - Scriba et al 2020 - report 3 patients with CANVAS from 2 families (2 brothers who reside in Indonesia, but are of Chinese descent, and a isolated female proband from the island nation of Niue) , with a novel, likely pathogenic RFC1 repeat motif (ACAGG)exp. These patients show additional clinical features including fasciculations and elevated creatine kinase levels. They share the core haplotype described in Cortese et al 2019 and Beecroft et al 2020. The RFC1 (ACAGG) motif was found in 7 individuals from 26 745 samples from gnomAD v3; 2 African, 4 South Asian, 1 East Asian.

PMID: 32694621 - Tsuchiya et al 2020 - reports a RFC1 (ACAGG) exp in 1 Japanese individual with sporadic CANVAS.
DDG2P v2.53 FGF5 Anna de Burca gene: FGF5 was added
gene: FGF5 was added to DDG2P. Sources: Literature
Mode of inheritance for gene: FGF5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FGF5 were set to PMID: 24989505
Phenotypes for gene: FGF5 were set to Hypertrichosis; long eyelashes
Penetrance for gene: FGF5 were set to Complete
Review for gene: FGF5 was set to GREEN
Added comment: Segregates with phenotype in two consanguineous families in publication attached. Additional unpublished case with same phenotype.
Sources: Literature
Hereditary ataxia with onset in adulthood v2.130 RFC1 Eleanor Williams reviewed gene: RFC1: Rating: AMBER; Mode of pathogenicity: None; Publications: 30926972, 31824583, 32851396, 32582864, 33969391; Phenotypes: Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome, OMIM:614575, cerebellar ataxia, neuropathy, and vestibular areflexia syndrome, MONDO:0013809, chronic idiopathic axonal polyneuropathy, chronic polyneuropathy, MONDO:0003335; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
DDG2P v2.53 CNKSR2 Dmitrijs Rots reviewed gene: CNKSR2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34266427; Phenotypes: Developmental delay, intellectual disability, seizures; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Ataxia and cerebellar anomalies - narrow panel v2.278 COQ4 Dmitrijs Rots gene: COQ4 was added
gene: COQ4 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Mode of inheritance for gene: COQ4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COQ4 were set to PMID: 30225196; 33704555; 30847826
Phenotypes for gene: COQ4 were set to Childhood onset ataxia
Penetrance for gene: COQ4 were set to Complete
Review for gene: COQ4 was set to GREEN
Added comment: The phenotype of COQ4 deficiency is very broad. In the three publications, at 6 individuals from 4 families are reported as having childhood onset ataxia.
Sources: Literature
Hereditary Erythrocytosis v1.35 SH2B3 Dmitrijs Rots reviewed gene: SH2B3: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 34440325, 34021251; Phenotypes: Myeloproliferative neoplasm; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Erythrocytosis v1.35 SLC30A10 Dmitrijs Rots gene: SLC30A10 was added
gene: SLC30A10 was added to Hereditary Erythrocytosis. Sources: Literature
Mode of inheritance for gene: SLC30A10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC30A10 were set to PMID: 22341971; 22341972
Phenotypes for gene: SLC30A10 were set to Erythrocytosis; Polycytemia; Hypermanganesemia; Parkinsonism; Dystonia; Liver disease
Review for gene: SLC30A10 was set to GREEN
Added comment: In 6 individuals from two families and 14 individuals from 8 families reported in in 22341971 and 22341972, respectively - all have erythrocytosis/polycytemia.
Sources: Literature
Hereditary Erythrocytosis v1.35 PIEZO1 Dmitrijs Rots gene: PIEZO1 was added
gene: PIEZO1 was added to Hereditary Erythrocytosis. Sources: Literature
Mode of inheritance for gene: PIEZO1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PIEZO1 were set to PMID: 33181827
Phenotypes for gene: PIEZO1 were set to Erythrocytosis
Penetrance for gene: PIEZO1 were set to unknown
Mode of pathogenicity for gene: PIEZO1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: PIEZO1 was set to GREEN
Added comment: Pathogenic variants (gain-of-function missense) in the PIEZO1 has been previously identified as a cause of hereditary xerocytosis. Recently, it has been Identified that similar (likely) pathogenic GoF missense variants likely causes erythrocytosis in 5 individuals. Functional analysis confirms pathogenicity of the variants. Patients also displayed features of hereditary xerocytosis.
Sources: Literature
Hereditary Erythrocytosis v1.35 BPGM Dmitrijs Rots reviewed gene: BPGM: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29790589; Phenotypes: Erythrocytosis; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v1.67 HEXB Dmitrijs Rots reviewed gene: HEXB: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20472204; Phenotypes: Sandhoff disease, neuropathy, ataxia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Corneal dystrophy v1.7 TCF4 Dmitrijs Rots reviewed gene: TCF4: Rating: RED; Mode of pathogenicity: Other; Publications: ; Phenotypes: ; Mode of inheritance: None
Corneal dystrophy v1.7 TCF4 Sarah Leigh Added comment: Comment on publications: Also https://doi.org/10.3390/genes12121918 (no PMID available 30th Dec 2021).
Corneal dystrophy v1.7 TCF4 Sarah Leigh Publications for gene: TCF4 were set to 29526280; 26401622
Malformations of cortical development v2.100 ENO1 Ivone Leong Classified gene: ENO1 as Red List (low evidence)
Malformations of cortical development v2.100 ENO1 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is not associated with a phenotype in OMIM or Gene2Phenotype. There is currently not enough evidence to support a gene-disease association. This gene has been given a Red rating.
Malformations of cortical development v2.100 ENO1 Ivone Leong Gene: eno1 has been classified as Red List (Low Evidence).
Malformations of cortical development v2.99 ENO1 Ivone Leong Phenotypes for gene: ENO1 were changed from Polymicrogyria to Polymicrogyria, MONDO:0000087
Hereditary neuropathy or pain disorder v1.67 HEXB Evan Reid edited their review of gene: HEXB: Changed rating: GREEN
Hereditary neuropathy or pain disorder v1.67 HEXA Evan Reid gene: HEXA was added
gene: HEXA was added to Hereditary neuropathy NOT PMP22 copy number. Sources: Literature
Mode of inheritance for gene: HEXA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HEXA were set to PMID: 28739864; 18642377
Penetrance for gene: HEXA were set to Complete
Review for gene: HEXA was set to GREEN
Added comment: Both HEXA and HEXB autosomal recessive mutations can be associated with a late onset motor neuropathy, sometimes quite mild and sometimes resembling ALS. We missed diagnosis of a patient with a late onset motor neuropathy as HEXB is not on the neuropathy panel. I would suggest that HEXA and HEXB should both be included on this panel.
Sources: Literature
Hereditary neuropathy or pain disorder v1.67 HEXB Evan Reid reviewed gene: HEXB: Rating: ; Mode of pathogenicity: None; Publications: PMID: 31512525, 20798201, 2795083; Phenotypes: ALS, motor neuronopathy; Mode of inheritance: None
Hereditary neuropathy or pain disorder v1.67 HEXB Evan Reid gene: HEXB was added
gene: HEXB was added to Hereditary neuropathy NOT PMP22 copy number. Sources: Literature
Mode of inheritance for gene: HEXB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HEXB were set to PMID: 31512525
Penetrance for gene: HEXB were set to Complete
Pigmentary skin disorders v1.37 SMARCAL1 Ivone Leong Tag Q4_21_NHS_review tag was added to gene: SMARCAL1.
Pigmentary skin disorders v1.37 TFE3 Ivone Leong Tag Q4_21_NHS_review tag was added to gene: TFE3.
Pigmentary skin disorders v1.37 USP9X Ivone Leong Tag Q4_21_rating tag was added to gene: USP9X.
Tag Q4_21_NHS_review tag was added to gene: USP9X.
Pigmentary skin disorders v1.37 USP9X Ivone Leong Classified gene: USP9X as Amber List (moderate evidence)
Pigmentary skin disorders v1.37 USP9X Ivone Leong Added comment: Comment on list classification: New gene added by Tom Cullup (Great Ormond Street Hospital). This gene is associated with a phenotype in OMIM and Gene2Phenotype (probable). There is enough evidence to support a gene-disease association, this gene should be rated Green at the next review.
Pigmentary skin disorders v1.37 USP9X Ivone Leong Gene: usp9x has been classified as Amber List (Moderate Evidence).
Pigmentary skin disorders v1.36 USP9X Ivone Leong Phenotypes for gene: USP9X were changed from Intellectual developmental disorder, X-linked 99, syndromic, female-restricted, OMIM:300968; Intellectual developmental disorder, X-linked 99, OMIM:300072 to Intellectual developmental disorder, X-linked 99, syndromic, female-restricted, OMIM:300968
Pigmentary skin disorders v1.35 USP9X Ivone Leong Phenotypes for gene: USP9X were changed from INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED 99, SYNDROMIC, FEMALE-RESTRICTED to Intellectual developmental disorder, X-linked 99, syndromic, female-restricted, OMIM:300968; Intellectual developmental disorder, X-linked 99, OMIM:300072
Pigmentary skin disorders v1.34 TFE3 Ivone Leong Tag Q4_21_rating tag was added to gene: TFE3.
Pigmentary skin disorders v1.34 TFE3 Ivone Leong Classified gene: TFE3 as Amber List (moderate evidence)
Pigmentary skin disorders v1.34 TFE3 Ivone Leong Added comment: Comment on list classification: New gene added by Tom Cullup (Great Ormond Street Hospital). This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype (confirmed). There is enough evidence to support a gene-disease association (12/17 patients have skin pigmentation abnormalities), this gene should be Green at the next review.
Pigmentary skin disorders v1.34 TFE3 Ivone Leong Gene: tfe3 has been classified as Amber List (Moderate Evidence).
Intellectual disability v3.1475 HMGB1 Dmitrijs Rots reviewed gene: HMGB1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
DDG2P v2.53 PBX1 Dmitrijs Rots gene: PBX1 was added
gene: PBX1 was added to DDG2P. Sources: Literature
Mode of inheritance for gene: PBX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PBX1 were set to Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay
Review for gene: PBX1 was set to GREEN
Added comment: Syndromic gene. Most of the individuals present with developmental delay, according to OMIM.
Sources: Literature
Monogenic hearing loss v2.209 PBX1 Dmitrijs Rots gene: PBX1 was added
gene: PBX1 was added to Hearing loss. Sources: Literature
Mode of inheritance for gene: PBX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PBX1 were set to Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay
Review for gene: PBX1 was set to GREEN
Added comment: Well known disease gene. As OMIM disease name suggests, hearing loss with ear abnormalities is common (reported in at least 5 cases).
Sources: Literature
Pigmentary skin disorders v1.33 TFE3 Ivone Leong Phenotypes for gene: TFE3 were changed from Intellectual disability with pigmentary mosaicism and storage disorder-like features to Intellectual developmental disorder, X-linked, syndromic, with pigmentary mosaicism and coarse facies, OMIM:301066
Pigmentary skin disorders v1.32 SMARCAL1 Ivone Leong Tag Q4_21_rating tag was added to gene: SMARCAL1.
Pigmentary skin disorders v1.32 SMARCAL1 Ivone Leong Classified gene: SMARCAL1 as Amber List (moderate evidence)
Pigmentary skin disorders v1.32 SMARCAL1 Ivone Leong Added comment: Comment on list classification: New gene added by Tom Cullup (Great Ormond Street Hospital). This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype (confirmed). There are >3 unrelated cases and PMID:20301550 reports that ~70% of patients have hyperpigmented macules. Therefore, there is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Pigmentary skin disorders v1.32 SMARCAL1 Ivone Leong Gene: smarcal1 has been classified as Amber List (Moderate Evidence).
Pigmentary skin disorders v1.31 SMARCAL1 Ivone Leong Publications for gene: SMARCAL1 were set to 11799392
Pigmentary skin disorders v1.30 SMARCAL1 Ivone Leong Phenotypes for gene: SMARCAL1 were changed from SCHIMKE IMMUNOOSSEOUS DYSPLASIA to Schimke immunoosseous dysplasia, OMIM:242900
IUGR and IGF abnormalities v1.46 PAPPA2 Ivone Leong Added comment: Comment on publications: Added new publication PMID:33875846
IUGR and IGF abnormalities v1.46 PAPPA2 Ivone Leong Publications for gene: PAPPA2 were set to 26902202
IUGR and IGF abnormalities v1.45 KANSL1 Ivone Leong Classified gene: KANSL1 as Green List (high evidence)
IUGR and IGF abnormalities v1.45 KANSL1 Ivone Leong Added comment: Comment on list classification: New gene added by Andžela Lazdāne (Children's Clinical University Hospital of Latvia). This gene is assiociated with a relevant phenotype in OMIM and Gene2Phenotype (confirmed). There is enough evidence to support a gene-disease association. This gene has been given a Green rating.
IUGR and IGF abnormalities v1.45 KANSL1 Ivone Leong Gene: kansl1 has been classified as Green List (High Evidence).
IUGR and IGF abnormalities v1.44 KANSL1 Ivone Leong Added comment: Comment on publications: PMID: 26306646. Additional 12 cases with de novo variants in KANSL1 causing disease, which further indicates that haploinsufficiency for KANSL1 is sufficient to cause the core phenotype.
IUGR and IGF abnormalities v1.44 KANSL1 Ivone Leong Publications for gene: KANSL1 were set to 22544363
IUGR and IGF abnormalities v1.43 KANSL1 Ivone Leong Publications for gene: KANSL1 were set to PMID: 22544363
IUGR and IGF abnormalities v1.42 KANSL1 Ivone Leong Phenotypes for gene: KANSL1 were changed from Koolen-De Vries syndrome; Facial features; Delayed psychomotor development; Intellectual disability to Koolen-De Vries syndrome, OMIM:610443; Facial features; Delayed psychomotor development; Intellectual disability
Primary ovarian insufficiency v1.60 SYCE1 Ivone Leong Classified gene: SYCE1 as Green List (high evidence)
Primary ovarian insufficiency v1.60 SYCE1 Ivone Leong Added comment: Comment on list classification: This gene is associated with a phenotype in OMIM but not in Gene2Phenotype. There is enough evidence to support a gene-disease association (2 cases + 1 animal model). Therefore, this gene has been promoted from Amber to Green.
Primary ovarian insufficiency v1.60 SYCE1 Ivone Leong Gene: syce1 has been classified as Green List (High Evidence).
Primary ovarian insufficiency v1.59 SYCE1 Ivone Leong Added comment: Comment on publications: PMID: 32917591. Authors made knockin mice with the mouse equivalent variant as Q241X seen in PMID:25062452. Both male and female homozygous mutant mice were infertile and replicated the human phenotype.

PMID:34718620. An additional case. Patient is compound heterozygous for variants in SYCE1.
Primary ovarian insufficiency v1.59 SYCE1 Ivone Leong Publications for gene: SYCE1 were set to 25062452
Primary ovarian insufficiency v1.58 SYCE1 Ivone Leong Phenotypes for gene: SYCE1 were changed from Premature ovarian failure 12616947 to ?Premature ovarian failure 12, OMIM:616947
Primary ovarian insufficiency v1.57 C14orf39 Ivone Leong Classified gene: C14orf39 as Green List (high evidence)
Primary ovarian insufficiency v1.57 C14orf39 Ivone Leong Added comment: Comment on list classification: Promoted from Amber to Green. There is now enough evidence to support a gene-disease association (2 cases + 1 animal model). This gene has been promoted to Green.
Primary ovarian insufficiency v1.57 C14orf39 Ivone Leong Gene: c14orf39 has been classified as Green List (High Evidence).
Primary ovarian insufficiency v1.56 C14orf39 Ivone Leong Publications for gene: C14orf39 were set to 33508233; 27796301
Intellectual disability v3.1475 PHF6 Ivone Leong reviewed gene: PHF6: Rating: ; Mode of pathogenicity: None; Publications: 24092917, 25099957; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability v3.1475 PHF6 Ivone Leong Phenotypes for gene: PHF6 were changed from Borjeson-Forssman-Lehmann syndrome, 301900; BOERJESON-FORSSMAN-LEHMANN SYNDROME (BFLS) to Borjeson-Forssman-Lehmann syndrome, OMIM:301900
Intellectual disability v3.1474 PHF6 Ivone Leong Publications for gene: PHF6 were set to
Intellectual disability v3.1473 PHF6 Ivone Leong Tag Q4_21_MOI tag was added to gene: PHF6.
DDG2P v2.53 PHF6 Ivone Leong reviewed gene: PHF6: Rating: ; Mode of pathogenicity: None; Publications: 24092917, 25099957; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Fetal anomalies v1.819 PHF6 Ivone Leong Tag Q4_21_MOI tag was added to gene: PHF6.
Fetal anomalies v1.819 PHF6 Ivone Leong reviewed gene: PHF6: Rating: ; Mode of pathogenicity: None; Publications: 24092917, 25099957; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Fetal anomalies v1.819 PHF6 Ivone Leong Publications for gene: PHF6 were set to
Fetal anomalies v1.818 PHF6 Ivone Leong Phenotypes for gene: PHF6 were changed from BOERJESON-FORSSMAN-LEHMANN SYNDROME to Borjeson-Forssman-Lehmann syndrome, OMIM:301900
Severe early-onset obesity v2.46 PHF6 Ivone Leong Tag Q4_21_MOI tag was added to gene: PHF6.
Severe early-onset obesity v2.46 PHF6 Ivone Leong reviewed gene: PHF6: Rating: ; Mode of pathogenicity: None; Publications: 24092917, 25099957; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Severe early-onset obesity v2.46 PHF6 Ivone Leong Publications for gene: PHF6 were set to
Pigmentary skin disorders v1.29 PHF6 Ivone Leong Publications for gene: PHF6 were set to 24092917
Pigmentary skin disorders v1.28 PHF6 Ivone Leong Tag Q4_21_rating tag was added to gene: PHF6.
Tag Q4_21_NHS_review tag was added to gene: PHF6.
Pigmentary skin disorders v1.28 PHF6 Ivone Leong Classified gene: PHF6 as Amber List (moderate evidence)
Pigmentary skin disorders v1.28 PHF6 Ivone Leong Added comment: Comment on list classification: New gene added by Tom Cullup (Great Ormond Street Hospital). This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype (confirmed). There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Pigmentary skin disorders v1.28 PHF6 Ivone Leong Gene: phf6 has been classified as Amber List (Moderate Evidence).
Childhood onset hereditary spastic paraplegia v2.121 RNASEH2B Arina Puzriakova Publications for gene: RNASEH2B were set to 30223285; 25243380; 29691679; 28762473
Childhood onset hereditary spastic paraplegia v2.120 RNASEH2B Arina Puzriakova Classified gene: RNASEH2B as Amber List (moderate evidence)
Childhood onset hereditary spastic paraplegia v2.120 RNASEH2B Arina Puzriakova Added comment: Comment on list classification: Sufficient evidence of childhood-onset spasticity associated with variants in this gene. Upgraded from Red to Amber but should be promoted to Green at the next GMS panel update.
Childhood onset hereditary spastic paraplegia v2.120 RNASEH2B Arina Puzriakova Gene: rnaseh2b has been classified as Amber List (Moderate Evidence).
Childhood onset hereditary spastic paraplegia v2.119 RNASEH2B Arina Puzriakova Tag Q4_21_rating tag was added to gene: RNASEH2B.
Pigmentary skin disorders v1.27 PHF6 Ivone Leong Phenotypes for gene: PHF6 were changed from BORJESON-FORSSMAN-LEHMANN SYNDROME; Fine and whorled Blaschko-linear hypo or hyperpigmentation to Borjeson-Forssman-Lehmann syndrome, OMIM:301900; Fine and whorled Blaschko-linear hypo or hyperpigmentation
Childhood onset hereditary spastic paraplegia v2.119 RNASEH2B Arina Puzriakova Phenotypes for gene: RNASEH2B were changed from Aicardi-Goutieres syndrome 2, 610181; spastic paraparesis to Aicardi-Goutieres syndrome 2, OMIM:61018
Pigmentary skin disorders v1.26 NDUFB11 Ivone Leong Tag Q4_21_expert_review tag was added to gene: NDUFB11.
Tag Q4_21_NHS_review tag was added to gene: NDUFB11.
Pigmentary skin disorders v1.26 NDUFB11 Ivone Leong Classified gene: NDUFB11 as Amber List (moderate evidence)
Pigmentary skin disorders v1.26 NDUFB11 Ivone Leong Added comment: Comment on list classification: New gene added by Tom Cullup (Great Ormond Street Hospital). This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype (probable). There is currently only 2 published cases of patients with Linear skin defects with multiple congenital anomalies 3. This gene is also associated with Histiocytoid cardiomyopathy and Lactic acidosis and sideroblastic anemia and patients with these diseases do not have signs of skin defects. Therefore, there is currently not enough evidence to support a gene-disease association. This gene has been given an Amber rating.
Pigmentary skin disorders v1.26 NDUFB11 Ivone Leong Gene: ndufb11 has been classified as Amber List (Moderate Evidence).
Pigmentary skin disorders v1.25 NDUFB11 Ivone Leong Phenotypes for gene: NDUFB11 were changed from Linear Skin Defects with Multiple Congenital Anomalies to Linear skin defects with multiple congenital anomalies 3, OMIM:300952
Early onset dystonia v1.99 RNASEH2B Arina Puzriakova Phenotypes for gene: RNASEH2B were changed from Dystonia to Aicardi-Goutieres syndrome 2, OMIM:61018
White matter disorders and cerebral calcification - narrow panel v1.220 RNASEH2B Arina Puzriakova Phenotypes for gene: RNASEH2B were changed from Aicardi-Goutieres Syndrome; General Leukodystrophy & Mitochondrial Leukoencephalopathy; Aicardi-Goutieres syndrome 2 to Aicardi-Goutieres syndrome 2, OMIM:610181
Adult onset leukodystrophy v1.36 RNASEH2B Arina Puzriakova Phenotypes for gene: RNASEH2B were changed from Aicardi-Goutieres syndrome 2, 610181 to Aicardi-Goutieres syndrome 2, OMIM:610181
Primary immunodeficiency or monogenic inflammatory bowel disease v2.498 RNASEH2B Arina Puzriakova Phenotypes for gene: RNASEH2B were changed from Aicardi-Goutieres syndrome 2 610181; Type 1 interferonopathies; Classical AGS, SP; Autoinflammatory Disorders to Aicardi-Goutieres syndrome 2, OMIM:610181
Intracerebral calcification disorders v1.34 RNASEH2B Arina Puzriakova Phenotypes for gene: RNASEH2B were changed from Aicardi-Goutieres syndrome 2; Aicardi-Goutieres Syndrome to Aicardi-Goutieres syndrome 2, OMIM:610181
Inherited white matter disorders v1.150 RNASEH2B Arina Puzriakova Phenotypes for gene: RNASEH2B were changed from Aicardi-Goutieres Syndrome; General Leukodystrophy & Mitochondrial Leukoencephalopathy; Aicardi-Goutieres syndrome 2 to Aicardi-Goutieres syndrome 2, OMIM:610181
Hereditary spastic paraplegia v1.276 RNASEH2B Arina Puzriakova Phenotypes for gene: RNASEH2B were changed from Aicardi-Goutieres syndrome 2, 610181; spastic paraparesis to Aicardi-Goutieres syndrome 2, OMIM:610181
Likely inborn error of metabolism v2.203 RNASEH2B Arina Puzriakova Phenotypes for gene: RNASEH2B were changed from Intellectual disability; (Disorders of nucleotide metabolism, Aicardi-Gouti res Syndrome) AGS2; Intracerebral calcification disorders; Inherited white matter disorders to Aicardi-Goutieres syndrome 2, OMIM:610181
Adult onset neurodegenerative disorder v2.257 RNASEH2B Arina Puzriakova Phenotypes for gene: RNASEH2B were changed from Dystonia to Aicardi-Goutieres syndrome 2, OMIM:610181; Dystonia (onset in infancy)
Undiagnosed metabolic disorders v1.501 RNASEH2B Arina Puzriakova Phenotypes for gene: RNASEH2B were changed from (Disorders of nucleotide metabolism, Aicardi-Gouti res Syndrome) AGS2; Inherited white matter disorders; Intellectual disability; Intracerebral calcification disorders to Aicardi-Goutieres syndrome 2, OMIM:610181
Intellectual disability v3.1473 RNASEH2B Arina Puzriakova Phenotypes for gene: RNASEH2B were changed from Aicardi-Goutieres syndrome 2, 610181; AICARDI-GOUTIERES SYNDROME 2 to Aicardi-Goutieres syndrome 2, OMIM:610181
Fetal anomalies v1.817 RNASEH2B Arina Puzriakova Phenotypes for gene: RNASEH2B were changed from AICARDI-GOUTIERES SYNDROME 2 to Aicardi-Goutieres syndrome 2, OMIM:610181
Early onset or syndromic epilepsy v2.477 RNASEH2B Arina Puzriakova Phenotypes for gene: RNASEH2B were changed from Aicardi-Goutieres syndrome 2, 610181 to Aicardi-Goutieres syndrome 2, OMIM:610181
Adult onset dystonia, chorea or related movement disorder v1.161 RNASEH2B Arina Puzriakova Phenotypes for gene: RNASEH2B were changed from Aicardi-Goutieres syndrome 2, 610181; Dystonia to Aicardi-Goutieres syndrome 2, OMIM:610181; Dystonia (onset in infancy)
Adult onset dystonia, chorea or related movement disorder v1.160 RNASEH2B Arina Puzriakova Mode of inheritance for gene: RNASEH2B was changed from to BIALLELIC, autosomal or pseudoautosomal
Childhood onset dystonia, chorea or related movement disorder v1.204 RNASEH2B Arina Puzriakova Phenotypes for gene: RNASEH2B were changed from Aicardi-Goutieres syndrome 2, 610181 to Aicardi-Goutieres syndrome 2, OMIM:610181
Childhood onset hereditary spastic paraplegia v2.118 RAB3GAP2 Arina Puzriakova Phenotypes for gene: RAB3GAP2 were changed from spastic paraplegia to Martsolf syndrome 1, OMIM:212720
Hereditary spastic paraplegia v1.275 RAB3GAP2 Arina Puzriakova Phenotypes for gene: RAB3GAP2 were changed from spastic paraplegia; Warburg micro syndrome 2, 614225 to Martsolf syndrome 1, OMIM:212720; Warburg micro syndrome 2, OMIM:614225
Adult onset hereditary spastic paraplegia v1.88 RAB3GAP2 Arina Puzriakova Phenotypes for gene: RAB3GAP2 were changed from spastic paraplegia; Warburg micro syndrome 2, 614225 to Warburg micro syndrome 2, OMIM:614225
Early onset or syndromic epilepsy v2.476 RAB3GAP2 Arina Puzriakova Mode of inheritance for gene: RAB3GAP2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v2.475 RAB3GAP2 Arina Puzriakova Phenotypes for gene: RAB3GAP2 were changed from to Martsolf syndrome 1, OMIM:212720; Warburg micro syndrome 2, OMIM:614225
Malformations of cortical development v2.98 RAB3GAP2 Arina Puzriakova Phenotypes for gene: RAB3GAP2 were changed from Warburg micro syndrome 2, MIM# 614225 to Warburg micro syndrome 2, OMIM:614225
Adult onset neurodegenerative disorder v2.256 RAB3GAP2 Arina Puzriakova Phenotypes for gene: RAB3GAP2 were changed from spastic paraplegia to Martsolf syndrome 1, OMIM:212720
Skeletal dysplasia v2.159 RAB3GAP2 Arina Puzriakova Phenotypes for gene: RAB3GAP2 were changed from Martsolf syndrome to Martsolf syndrome 1, OMIM:212720
Skeletal dysplasia v2.158 RAB3GAP2 Arina Puzriakova Mode of inheritance for gene: RAB3GAP2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Dilated Cardiomyopathy and conduction defects v1.75 RAB3GAP2 Arina Puzriakova Phenotypes for gene: RAB3GAP2 were changed from 212720; 614225 to Martsolf syndrome 1, OMIM:212720; Warburg micro syndrome 2, OMIM:614225
Corneal abnormalities v1.10 RAB3GAP2 Arina Puzriakova Phenotypes for gene: RAB3GAP2 were changed from Martsolf syndrome 212720; Warburg micro syndrome 2 614225 to Martsolf syndrome 1, OMIM:212720; Warburg micro syndrome 2, OMIM:614225
Structural eye disease v1.94 RAB3GAP2 Arina Puzriakova Phenotypes for gene: RAB3GAP2 were changed from Martsolf syndrome, 212720; Warburg micro syndrome 2, 614225; Martsolf syndrome, 212720Warburg micro syndrome 2, 614225; Warburg Micro Syndrome to Martsolf syndrome 1, OMIM:212720; Warburg micro syndrome 2, OMIM:614225
Anophthalmia or microphthalmia v1.43 RAB3GAP2 Arina Puzriakova Phenotypes for gene: RAB3GAP2 were changed from Warburg Micro Syndrome; Martsolf syndrome, 212720Warburg micro syndrome 2, 614225 to Martsolf syndrome 1, OMIM:212720; Warburg micro syndrome 2, OMIM:614225
Intellectual disability v3.1472 RAB3GAP2 Arina Puzriakova Phenotypes for gene: RAB3GAP2 were changed from Martsolf syndrome, 212720Warburg micro syndrome 2, 614225; MARTSOLF SYNDROME (MARTS) to Martsolf syndrome 1, OMIM:212720; Warburg micro syndrome 2, OMIM:614225
Bilateral congenital or childhood onset cataracts v2.90 RAB3GAP2 Arina Puzriakova Phenotypes for gene: RAB3GAP2 were changed from Martsolf syndrome; Warburg micro syndrome 2; Warburg Micro syndrome-2 to Martsolf syndrome 1, OMIM:212720; Warburg micro syndrome 2, OMIM:614225
Ataxia and cerebellar anomalies - narrow panel v2.278 MAPK8IP3 Arina Puzriakova Classified gene: MAPK8IP3 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.278 MAPK8IP3 Arina Puzriakova Added comment: Comment on list classification: 18 individuals from 17 families reported with de novo variants in this gene (PMIDs: 30612693; 30945334) of which 3 subjects displayed cerebellar atrophy on brain MRI and 2 had ataxia. Onset in childhood. Overall there is sufficient evidence to promote this gene to Green at the next GMS panel update.
Ataxia and cerebellar anomalies - narrow panel v2.278 MAPK8IP3 Arina Puzriakova Gene: mapk8ip3 has been classified as Amber List (Moderate Evidence).
Hereditary ataxia with onset in adulthood v2.130 MAPK8IP3 Arina Puzriakova Classified gene: MAPK8IP3 as Green List (high evidence)
Hereditary ataxia with onset in adulthood v2.130 MAPK8IP3 Arina Puzriakova Added comment: Comment on list classification: 18 individuals from 17 families reported with de novo variants in this gene (PMIDs: 30612693; 30945334) of which 3 subjects displayed cerebellar atrophy on brain MRI and 2 had ataxia. However, this is a childhood onset condition and literature search did not reveal any evidence of adult onset ataxia associated with this gene. Therefore, MAPK8IP3 should be downgraded from Green here and added to the childhood cerebellar anomalies panel.
Hereditary ataxia with onset in adulthood v2.130 MAPK8IP3 Arina Puzriakova Gene: mapk8ip3 has been classified as Green List (High Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.277 MAPK8IP3 Arina Puzriakova Entity copied from Hereditary ataxia - adult onset v2.129
Ataxia and cerebellar anomalies - narrow panel v2.277 MAPK8IP3 Arina Puzriakova gene: MAPK8IP3 was added
gene: MAPK8IP3 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Wessex and West Midlands GLH,Expert Review Green,NHS GMS
Q4_21_rating tags were added to gene: MAPK8IP3.
Mode of inheritance for gene: MAPK8IP3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAPK8IP3 were set to 30612693; 30945334
Phenotypes for gene: MAPK8IP3 were set to Neurodevelopmental disorder with or without variable brain abnormalities, OMIM:618443
Hereditary ataxia with onset in adulthood v2.129 MAPK8IP3 Arina Puzriakova Publications for gene: MAPK8IP3 were updated from to 30612693; 30945334
Tag Q4_21_rating tag was added to MAPK8IP3.
Childhood onset hereditary spastic paraplegia v2.117 MAPK8IP3 Arina Puzriakova Phenotypes for gene: MAPK8IP3 were changed from Neurodevelopmental disorder with or without variable brain abnormalities, MIM# 618443 to Neurodevelopmental disorder with or without variable brain abnormalities, OMIM:618443
Childhood onset hereditary spastic paraplegia v2.116 MAPK8IP3 Arina Puzriakova Tag Q4_21_rating tag was added to gene: MAPK8IP3.
Childhood onset hereditary spastic paraplegia v2.116 MAPK8IP3 Arina Puzriakova Classified gene: MAPK8IP3 as Amber List (moderate evidence)
Childhood onset hereditary spastic paraplegia v2.116 MAPK8IP3 Arina Puzriakova Added comment: Comment on list classification: 18 individuals from 17 families reported with de novo variants in this gene (PMIDs: 30612693; 30945334) of which 8 subjects presented with spasticity, among other features. Overall there is sufficient evidence to promote this gene to Green at the next GMS panel update.
Childhood onset hereditary spastic paraplegia v2.116 MAPK8IP3 Arina Puzriakova Gene: mapk8ip3 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.97 MAPK8IP3 Arina Puzriakova Tag Q4_21_rating tag was added to gene: MAPK8IP3.
Malformations of cortical development v2.97 MAPK8IP3 Arina Puzriakova Publications for gene: MAPK8IP3 were set to 30612693
Malformations of cortical development v2.96 MAPK8IP3 Arina Puzriakova Classified gene: MAPK8IP3 as Amber List (moderate evidence)
Malformations of cortical development v2.96 MAPK8IP3 Arina Puzriakova Added comment: Comment on list classification: 18 individuals from 17 families reported with de novo variants in this gene (PMIDs: 30612693; 30945334). Various brain malformations affecting both cerebral and cerebellar structures identified in all except four individuals. Overall there is sufficient evidence to promote this gene to Green at the next GMS panel update.
Malformations of cortical development v2.96 MAPK8IP3 Arina Puzriakova Gene: mapk8ip3 has been classified as Amber List (Moderate Evidence).
Intellectual disability v3.1471 MAPK8IP3 Arina Puzriakova Phenotypes for gene: MAPK8IP3 were changed from Abnormal muscle tone; Global developmental delay; Intellectual disability; Abnormality of nervous system morphology; Neurodevelopmental disorder with or without variable brain abnormalities, 618443 to Neurodevelopmental disorder with or without variable brain abnormalities, OMIM:618443
Hereditary ataxia with onset in adulthood v2.128 MAPK8IP3 Arina Puzriakova Phenotypes for gene: MAPK8IP3 were changed from Intellectual Disability with variable brain anomalies; Neurodevelopmental disorder with or without variable brain abnormalities, 618443 to Neurodevelopmental disorder with or without variable brain abnormalities, OMIM:618443
Malformations of cortical development v2.95 MAPK8IP3 Arina Puzriakova Phenotypes for gene: MAPK8IP3 were changed from Neurodevelopmental disorder with or without variable brain abnormalities OMIM# 605431 to Neurodevelopmental disorder with or without variable brain abnormalities, OMIM:618443
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v2.32 CAPN3 Dmitrijs Rots reviewed gene: CAPN3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32896923; Phenotypes: limb girdle muscle dystrophy; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Distal myopathies v1.38 SMPX Dmitrijs Rots gene: SMPX was added
gene: SMPX was added to Distal myopathies. Sources: Literature
Mode of inheritance for gene: SMPX was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SMPX were set to PMID: 33974137
Phenotypes for gene: SMPX were set to Distal myopathy
Penetrance for gene: SMPX were set to unknown
Mode of pathogenicity for gene: SMPX was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: SMPX was set to GREEN
Added comment: Hemizygous variants in 10 patients from 9 families with functional data.
Sources: Literature
Congenital myopathy v2.68 ACTN2 Dmitrijs Rots reviewed gene: ACTN2: Rating: ; Mode of pathogenicity: None; Publications: PMID: 34471957; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v2.32 ACTN2 Dmitrijs Rots gene: ACTN2 was added
gene: ACTN2 was added to Limb girdle muscular dystrophy. Sources: Literature
Mode of inheritance for gene: ACTN2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ACTN2 were set to PMID: 34471957; 30701273; 30900782
Phenotypes for gene: ACTN2 were set to Muscular dystrophy; hyperCKemia
Penetrance for gene: ACTN2 were set to unknown
Review for gene: ACTN2 was set to GREEN
Added comment: Multiple individuals from multiple families reported suggesting ACTN2 as both, monoallelic and biallelic cause of muscular dysctrophy.
Sources: Literature
Erythropoietic protoporphyria, mild variant v1.2 CLPX Aleš Maver gene: CLPX was added
gene: CLPX was added to Erythropoietic protoporphyria, mild variant. Sources: Other
Mode of inheritance for gene: CLPX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CLPX were set to 28874591
Penetrance for gene: CLPX were set to unknown
Mode of pathogenicity for gene: CLPX was set to Other
Review for gene: CLPX was set to RED
Added comment: Entry is based on a single report (PMID: 28874591) of a novel missense variant in CPLX gene (p.Gly298Asp) in a family with erythropoietic protoporphyria. The mutation is reported to occur in the ATPase active site of human CLPX, p.Gly298Asp, and it stated by authors that it results in pathological accumulation of the heme biosynthesis intermediate protoporphyrin IX (PPIX).Three heterozygous members of the family are reported - the proband is affected, while the two relatives have been reported to have free and zinc-PPIX accumulation in erythrocytes and associated mild photosensitivity, but are without the complete clinical symptoms of EPP.
Sources: Other
Familial chylomicronaemia syndrome (FCS) v1.19 APOB Sarah Leigh reviewed gene: APOB: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Likely inborn error of metabolism v2.202 APOB Sarah Leigh edited their review of gene: APOB: Added comment: The mode of inheritance for APOB should be both monoallelic and biallelic, as Hypercholesterolemia, familial, 2 OMIM:144010 is monoallelic and Hypobetalipoproteinemia OMIM:615558 is biallelic.; Changed rating: GREEN; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Undiagnosed metabolic disorders v1.500 APOB Sarah Leigh edited their review of gene: APOB: Added comment: The mode of inheritance for APOB should be both monoallelic and biallelic, as Hypercholesterolemia, familial, 2 OMIM:144010 is monoallelic and Hypobetalipoproteinemia OMIM:615558 is biallelic.; Changed rating: GREEN; Changed mode of pathogenicity: Other; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rare genetic inflammatory skin disorders v1.45 ECM1 Eleanor Williams Classified gene: ECM1 as Amber List (moderate evidence)
Rare genetic inflammatory skin disorders v1.45 ECM1 Eleanor Williams Added comment: Comment on list classification: Promoting from grey to amber, with a recommendation for a GREEN rating following GMS review. More than 3 cases reported with a plausible disease causing variant in the ECM1 gene and a Lipoid proteinosis phenotype.
Rare genetic inflammatory skin disorders v1.45 ECM1 Eleanor Williams Gene: ecm1 has been classified as Amber List (Moderate Evidence).
Rare genetic inflammatory skin disorders v1.44 ECM1 Eleanor Williams Phenotypes for gene: ECM1 were changed from Urbach-Wiethe disease to Urbach-Wiethe disease, OMIM:247100; lipoid proteinosis, MONDO:0009530
Rare genetic inflammatory skin disorders v1.43 ECM1 Eleanor Williams Publications for gene: ECM1 were set to 11929856
Rare genetic inflammatory skin disorders v1.42 ECM1 Eleanor Williams Tag Q4_21_rating tag was added to gene: ECM1.
Tag Q4_21_NHS_review tag was added to gene: ECM1.
Rare genetic inflammatory skin disorders v1.42 ECM1 Eleanor Williams reviewed gene: ECM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11929856, 28720532, 33159951; Phenotypes: Urbach-Wiethe disease, OMIM:247100, lipoid proteinosis, MONDO:0009530; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Undiagnosed metabolic disorders v1.500 APOB Sarah Leigh Tag Q4_21_MOI tag was added to gene: APOB.
Undiagnosed metabolic disorders v1.500 APOB Sarah Leigh Phenotypes for gene: APOB were changed from Hypercholesterolemia, familial, 2 144010; Hypobetalipoproteinemia 615558 to Hypercholesterolemia, familial, 2 OMIM:144010; hypercholesterolemia, autosomal dominant, type B MONDO:0007751; Hypobetalipoproteinemia OMIM:615558; familial hypobetalipoproteinemia 1 MONDO:0014252
Likely inborn error of metabolism v2.202 APOB Sarah Leigh Phenotypes for gene: APOB were changed from Hypercholesterolemia, familial, 2 144010; Hypobetalipoproteinemia 615558 to Hypercholesterolemia, familial, 2 OMIM:144010; hypercholesterolemia, autosomal dominant, type B MONDO:0007751; Hypobetalipoproteinemia OMIM:615558; familial hypobetalipoproteinemia 1 MONDO:0014252
Likely inborn error of metabolism v2.201 APOB Sarah Leigh Tag Q4_21_MOI tag was added to gene: APOB.
Mosaic skin disorders - deep sequencing v1.18 PORCN Eleanor Williams Tag Q4_21_NHS_review tag was added to gene: PORCN.
Mosaic skin disorders - deep sequencing v1.18 PTPN11 Eleanor Williams Tag Q4_21_NHS_review tag was added to gene: PTPN11.
Mosaic skin disorders - deep sequencing v1.18 BRAF Eleanor Williams Tag Q4_21_NHS_review tag was added to gene: BRAF.
Multiple monogenic benign skin tumours v1.18 NOTCH3 Eleanor Williams Tag Q4_21_expert_review tag was added to gene: NOTCH3.
Tag Q4_21_NHS_review tag was added to gene: NOTCH3.
Multiple monogenic benign skin tumours v1.18 NOTCH3 Eleanor Williams changed review comment from: Comment on list classification: Promoting from grey to amber. 1 case plus functional studies supporting the role of the reported NOTCH3 variant in disease.; to: Comment on list classification: Promoting from grey to amber. 1 case plus functional studies supporting the role of the reported NOTCH3 variant in disease. Note the eligibility criteria for the clinical indication will need to be expanded before promoting to green.
Multiple monogenic benign skin tumours v1.18 PDGFRB Eleanor Williams Classified gene: PDGFRB as Amber List (moderate evidence)
Multiple monogenic benign skin tumours v1.18 PDGFRB Eleanor Williams Added comment: Comment on list classification: Promoting this gene from grey (curator removed) to amber, with a green rating recommendation if approved by the GMS. Note the eligibility criteria for the clinical indication will need to be expanded before promoting to green.
Multiple monogenic benign skin tumours v1.18 PDGFRB Eleanor Williams Gene: pdgfrb has been classified as Amber List (Moderate Evidence).
Multiple monogenic benign skin tumours v1.17 PDGFRB Eleanor Williams Tag curated_removed was removed from gene: PDGFRB.
Multiple monogenic benign skin tumours v1.17 PDGFRB Eleanor Williams Phenotypes for gene: PDGFRB were changed from Infantile myofibromatosis to Myofibromatosis, infantile, 1, OMIM:228550; myofibromatosis, infantile, 1, MONDO:0009227
Multiple monogenic benign skin tumours v1.16 PDGFRB Eleanor Williams Publications for gene: PDGFRB were set to
Multiple monogenic benign skin tumours v1.15 PDGFRB Eleanor Williams Tag Q4_21_expert_review tag was added to gene: PDGFRB.
Tag Q4_21_rating tag was added to gene: PDGFRB.
Tag Q4_21_phenotype tag was added to gene: PDGFRB.
Tag Q4_21_NHS_review tag was added to gene: PDGFRB.
Multiple monogenic benign skin tumours v1.15 PDGFRB Eleanor Williams commented on gene: PDGFRB
Structural eye disease v1.93 NDUFB11 Ivone Leong Mode of inheritance for gene: NDUFB11 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)
Pigmentary skin disorders v1.24 HCCS Ivone Leong Classified gene: HCCS as Amber List (moderate evidence)
Pigmentary skin disorders v1.24 HCCS Ivone Leong Added comment: Comment on list classification: New gene added by Tom Cullup (Great Ormond Street Hospital). This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype (confirmed). There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Pigmentary skin disorders v1.24 HCCS Ivone Leong Gene: hccs has been classified as Amber List (Moderate Evidence).
Pigmentary skin disorders v1.23 HCCS Ivone Leong Tag Q4_21_rating tag was added to gene: HCCS.
COVID-19 research v1.90 FLNA Sarah Leigh gene: FLNA was added
gene: FLNA was added to COVID-19 research. Sources: Literature
Mode of inheritance for gene: FLNA was set to Unknown
Publications for gene: FLNA were set to DOI:10.3390/genes12111842
Review for gene: FLNA was set to AMBER
Added comment: DOI: 10.3390/genes12111842 reports: Results based on DSC and SSC metrics demonstrated a different selective pressure on three genes (MUC5AC, ABCA7, FLNA) between Qatari and Italian populations. This study highlighted the genetic differences between Qatari and Italian populations and identified a subset of genes involved in innate immunity and host-pathogen interaction.
Sources: Literature
COVID-19 research v1.89 MUC5AC Sarah Leigh Publications for gene: MUC5AC were set to 10.3390/genes12111842
COVID-19 research v1.88 ABCA7 Sarah Leigh gene: ABCA7 was added
gene: ABCA7 was added to COVID-19 research. Sources: Literature
Mode of inheritance for gene: ABCA7 was set to Unknown
Publications for gene: ABCA7 were set to DOI:10.3390/genes12111842
Review for gene: ABCA7 was set to AMBER
Added comment: DOI: 10.3390/genes12111842 reports: Results based on DSC and SSC metrics demonstrated a different selective pressure on three genes (MUC5AC, ABCA7, FLNA) between Qatari and Italian populations. This study highlighted the genetic differences between Qatari and Italian populations and identified a subset of genes involved in innate immunity and host-pathogen interaction.
Sources: Literature
COVID-19 research v1.87 MUC5AC Sarah Leigh gene: MUC5AC was added
gene: MUC5AC was added to COVID-19 research. Sources: Literature
Mode of inheritance for gene: MUC5AC was set to Unknown
Publications for gene: MUC5AC were set to 10.3390/genes12111842
Review for gene: MUC5AC was set to AMBER
Added comment: DOI: 10.3390/genes12111842 reports: Results based on DSC and SSC metrics demonstrated a different selective pressure on three genes (MUC5AC, ABCA7, FLNA) between Qatari and Italian populations. This study highlighted the genetic differences between Qatari and Italian populations and identified a subset of genes involved in innate immunity and host-pathogen interaction.
Sources: Literature
Multiple monogenic benign skin tumours v1.15 NOTCH3 Eleanor Williams Classified gene: NOTCH3 as Amber List (moderate evidence)
Multiple monogenic benign skin tumours v1.15 NOTCH3 Eleanor Williams Added comment: Comment on list classification: Promoting from grey to amber. 1 case plus functional studies supporting the role of the reported NOTCH3 variant in disease.
Multiple monogenic benign skin tumours v1.15 NOTCH3 Eleanor Williams Gene: notch3 has been classified as Amber List (Moderate Evidence).
Multiple monogenic benign skin tumours v1.14 NOTCH3 Eleanor Williams Phenotypes for gene: NOTCH3 were changed from MYOFIBROMATOSIS, INFANTILE, 2 to ?Myofibromatosis, infantile 2, OMIM:615293; myofibromatosis, infantile, 2, MONDO:0014122
Multiple monogenic benign skin tumours v1.13 NOTCH3 Eleanor Williams Publications for gene: NOTCH3 were set to 23731542
Multiple monogenic benign skin tumours v1.12 NOTCH3 Eleanor Williams changed review comment from: Provisionally associated with ?Myofibromatosis, infantile 2 #615293 (AD) in OMIM which they state is characterized by the development of benign tumors in the skin, muscle, bone, and viscera.

PMID: 23731542 - Martignetti et al 2013 - In a family with Infantile myofibromatosis exome sequencing identified a heterozygous variant in NOTCH along with another candidate variant. By performing Sanger sequencing of 16 family members (9 affected and 7 unaffected) they found that only NOTCH3 mutation c.4556T>C (p.Leu1519Pro) segregated appropriately with affected status.; to: Provisionally associated with ?Myofibromatosis, infantile 2 #615293 (AD) in OMIM which they state is characterized by the development of benign tumors in the skin, muscle, bone, and viscera.

PMID: 23731542 - Martignetti et al 2013 - In a family with Infantile myofibromatosis exome sequencing identified a heterozygous variant in NOTCH along with another candidate variant. By performing Sanger sequencing of 16 family members (9 affected and 7 unaffected) they found that only NOTCH3 mutation c.4556T>C (p.Leu1519Pro) segregated appropriately with affected status.

PMID: 33509954 - Wu et al 2021 - looked at the molecular consequences of the NOTCH3 L1519P mutation using HEK293 cells. The NOTCH3L1519P receptor generates enhanced downstream signaling in a ligand-independent manner, but is absent from the cell surface and accumulates in the endoplasmic reticulum instead. The protein with the variant upregulates PDGFRB expression in fibroblasts. This supports a functional link between Notch and PDGF dysregulation in Infantile myofibromatosis.
Multiple monogenic benign skin tumours v1.12 NOTCH3 Eleanor Williams edited their review of gene: NOTCH3: Changed publications to: 33509954, 23731542
Multiple monogenic benign skin tumours v1.12 NOTCH3 Eleanor Williams commented on gene: NOTCH3
Mosaic skin disorders - deep sequencing v1.18 PTPN11 Eleanor Williams Classified gene: PTPN11 as Amber List (moderate evidence)
Mosaic skin disorders - deep sequencing v1.18 PTPN11 Eleanor Williams Added comment: Comment on list classification: Leaving rating as amber, but with recommendation for green rating after GMS confirmation given the green review from NHS reviewer.
Mosaic skin disorders - deep sequencing v1.18 PTPN11 Eleanor Williams Gene: ptpn11 has been classified as Amber List (Moderate Evidence).
Mosaic skin disorders - deep sequencing v1.17 PTPN11 Eleanor Williams Phenotypes for gene: PTPN11 were changed from Noonan syndrome; Noonan syndrome with lentigines (LEOPARD); Phakomatosis pigmentovascularis (PPV), Noonan syndrome with lentigines (LEOPARD)(151100); Speckled lentiginous naevus syndrome (deletion) to Phakomatosis pigmentovascularis (PPV), MONDO:0017318; LEOPARD syndrome 1, OMIM:151100; Speckled lentiginous naevus syndrome (deletion)
Mosaic skin disorders - deep sequencing v1.16 PTPN11 Eleanor Williams Tag Q4_21_rating tag was added to gene: PTPN11.
Mosaic skin disorders - deep sequencing v1.16 PTPN11 Eleanor Williams Phenotypes for gene: PTPN11 were changed from Noonan syndrome; Noonan syndrome with lentigines (LEOPARD) to Noonan syndrome; Noonan syndrome with lentigines (LEOPARD); Phakomatosis pigmentovascularis (PPV), Noonan syndrome with lentigines (LEOPARD)(151100); Speckled lentiginous naevus syndrome (deletion)
Mosaic skin disorders - deep sequencing v1.15 PORCN Eleanor Williams Tag mosaicism tag was added to gene: PORCN.
Mosaic skin disorders - deep sequencing v1.15 PORCN Eleanor Williams Classified gene: PORCN as Amber List (moderate evidence)
Mosaic skin disorders - deep sequencing v1.15 PORCN Eleanor Williams Added comment: Comment on list classification: Promoting from grey to amber, but with a recommendation for a GREEN rating following GMS review.
Mosaic skin disorders - deep sequencing v1.15 PORCN Eleanor Williams Gene: porcn has been classified as Amber List (Moderate Evidence).
Mosaic skin disorders - deep sequencing v1.14 PORCN Eleanor Williams Tag Q4_21_rating tag was added to gene: PORCN.
Mosaic skin disorders - deep sequencing v1.14 PORCN Eleanor Williams Phenotypes for gene: PORCN were changed from Focal dermal hypoplasia (https://omim.org/entry/305600) to Focal dermal hypoplasia, OMIM:305600; focal dermal hypoplasia, MONDO:0010592
Mosaic skin disorders - deep sequencing v1.13 PORCN Eleanor Williams Publications for gene: PORCN were set to 17546030
Mosaic skin disorders - deep sequencing v1.12 PORCN Eleanor Williams edited their review of gene: PORCN: 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)
Childhood onset hereditary spastic paraplegia v2.115 IFIH1 Arina Puzriakova Tag Q4_21_rating tag was added to gene: IFIH1.
Childhood onset hereditary spastic paraplegia v2.115 IFIH1 Arina Puzriakova Classified gene: IFIH1 as Amber List (moderate evidence)
Childhood onset hereditary spastic paraplegia v2.115 IFIH1 Arina Puzriakova Added comment: Comment on list classification: Spasticity can be a prominent feature of Aicardi-Goutières syndrome (OMIM:615846) and has been reported as an early presenting sign in some cases. There has also been a case of spastic paraplegia without other common manifestations such as abnormal brain imaging and impaired cognitive development.

Overall there is value in including IFIH1 on this panel and therefore this gene should be promoted to Green at the next GMS panel update.
Childhood onset hereditary spastic paraplegia v2.115 IFIH1 Arina Puzriakova Gene: ifih1 has been classified as Amber List (Moderate Evidence).
Childhood onset hereditary spastic paraplegia v2.114 IFIH1 Arina Puzriakova Phenotypes for gene: IFIH1 were changed from Aicardi-Goutieres syndrome 7 MIM#615846 to Aicardi-Goutieres syndrome 7, OMIM:615846
Skeletal dysplasia v2.157 IFIH1 Arina Puzriakova Phenotypes for gene: IFIH1 were changed from Singleton-Merten syndrome 1, 182250 to Singleton-Merten syndrome 1, OMIM:182250
Early onset or syndromic epilepsy v2.474 IFIH1 Arina Puzriakova Phenotypes for gene: IFIH1 were changed from Aicardi-Goutieres syndrome 7, 615846; seizures to Aicardi-Goutieres syndrome 7, OMIM:615846
Fetal anomalies v1.816 IFIH1 Arina Puzriakova Phenotypes for gene: IFIH1 were changed from AICARDI-GOUTIERES SYNDROME 7; SINGLETON-MERTEN SYNDROME; Aicardi-Goutieres syndrome 7, 615846; Singleton-Merten syndrome 1, 182250 to Aicardi-Goutieres syndrome 7, OMIM:615846; Singleton-Merten syndrome 1, OMIM:182250
Mosaic skin disorders - deep sequencing v1.12 PORCN Eleanor Williams reviewed gene: PORCN: Rating: GREEN; Mode of pathogenicity: None; Publications: 17546030, 19309688; Phenotypes: Focal dermal hypoplasia, OMIM:305600; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v3.1470 IFIH1 Arina Puzriakova Phenotypes for gene: IFIH1 were changed from AICARDI-GOUTIERES SYNDROME 7 to Aicardi-Goutieres syndrome 7, OMIM:615846
Childhood onset dystonia, chorea or related movement disorder v1.203 IFIH1 Arina Puzriakova Phenotypes for gene: IFIH1 were changed from Aicardi-Goutieres syndrome 7 615846 to Aicardi-Goutieres syndrome 7, OMIM:615846
Adult onset dystonia, chorea or related movement disorder v1.159 IFIH1 Arina Puzriakova Phenotypes for gene: IFIH1 were changed from Aicardi-Goutieres syndrome 7 615846 to Aicardi-Goutieres syndrome 7, OMIM:615846
Inherited white matter disorders v1.149 IFIH1 Arina Puzriakova Phenotypes for gene: IFIH1 were changed from Aicardi-Goutieres Syndrome; Aicardi-Goutieres syndrome 7; General Leukodystrophy & Mitochondrial Leukoencephalopathy to Aicardi-Goutieres syndrome 7, OMIM:615846
Intracerebral calcification disorders v1.33 IFIH1 Arina Puzriakova Phenotypes for gene: IFIH1 were changed from Aicardi-Goutieres syndrome 7, 615846; Aicardi-Goutières, isolated spasticity, bilateral striatal necrosis to Aicardi-Goutieres syndrome 7, OMIM:615846
Structural basal ganglia disorders v1.26 IFIH1 Arina Puzriakova Phenotypes for gene: IFIH1 were changed from Aicardi-Goutieres syndrome 7 615846 to Aicardi-Goutieres syndrome 7, OMIM:615846
White matter disorders and cerebral calcification - narrow panel v1.219 IFIH1 Arina Puzriakova Phenotypes for gene: IFIH1 were changed from Aicardi-Goutieres Syndrome; General Leukodystrophy & Mitochondrial Leukoencephalopathy; Aicardi-Goutieres syndrome 7, 615846; Aicardi-Goutieres syndrome 7; Aicardi-Gouti res, isolated spasticity, bilateral striatal necrosis to Aicardi-Goutieres syndrome 7, OMIM:615846
COVID-19 research v1.86 IFIH1 Arina Puzriakova Phenotypes for gene: IFIH1 were changed from Rhinovirus and other RNA viruses (AR); Classical AGS, SLE, SP, SMS; Autoinflammatory Disorders; Aicardi-Goutieres syndrome 7 (AD); susceptibility to RNA viruses; Recurrent and prolonged infections; Defects in Intrinsic and Innate Immunity to Aicardi-Goutieres syndrome 7, OMIM:615846 (AD); Singleton-Merten syndrome 1, OMIM:182250 (AD); Susceptibility to RNA viruses (AR)
Primary immunodeficiency or monogenic inflammatory bowel disease v2.497 IFIH1 Arina Puzriakova Phenotypes for gene: IFIH1 were changed from Aicardi-Goutieres syndrome 7 (AD); Classical AGS, SLE, SP, SMS; Autoinflammatory Disorders; Rhinovirus and other RNA viruses (AR); susceptibility to RNA viruses; Defects in Intrinsic and Innate Immunity to Aicardi-Goutieres syndrome 7, OMIM:615846 (AD); Singleton-Merten syndrome 1, OMIM:182250 (AD); Susceptibility to RNA viruses (AR)
Arthrogryposis v3.145 IBA57 Arina Puzriakova Phenotypes for gene: IBA57 were changed from Multiple mitochondrial dysfunctions syndrome 3 615330 to Multiple mitochondrial dysfunctions syndrome 3, OMIM:615330
Inherited white matter disorders v1.148 IBA57 Arina Puzriakova Phenotypes for gene: IBA57 were changed from Multiple mitochondrial dysfunctions syndrome 3, 615330 to Multiple mitochondrial dysfunctions syndrome 3, OMIM:615330
Intellectual disability v3.1469 IBA57 Arina Puzriakova Phenotypes for gene: IBA57 were changed from Multiple mitochondrial dysfunctions syndrome 3, 615330; intellectual disability, seizures, loss of milestones to Multiple mitochondrial dysfunctions syndrome 3, OMIM:615330
Pyruvate dehydrogenase (PDH) deficiency v1.31 IBA57 Arina Puzriakova Phenotypes for gene: IBA57 were changed from MULTIPLE MITOCHONDRIAL DYSFUNCTIONS SYNDROME 3 OMIM:615330; multiple mitochondrial dysfunctions syndrome 3 MONDO:0014132 to Multiple mitochondrial dysfunctions syndrome 3, OMIM:615330
White matter disorders and cerebral calcification - narrow panel v1.218 IBA57 Arina Puzriakova Phenotypes for gene: IBA57 were changed from Multiple mitochondrial dysfunctions syndrome 3, 615330 to Multiple mitochondrial dysfunctions syndrome 3, OMIM:615330
Mitochondrial disorders v2.63 IBA57 Arina Puzriakova Phenotypes for gene: IBA57 were changed from ?Multiple mitochondrial dysfunctions syndrome 3, 615330; ?Spastic paraplegia 74, autosomal recessive to Multiple mitochondrial dysfunctions syndrome 3, OMIM:615330; ?Spastic paraplegia 74, autosomal recessive, OMIM:616451
Likely inborn error of metabolism v2.201 IBA57 Arina Puzriakova Phenotypes for gene: IBA57 were changed from ?Multiple mitochondrial dysfunctions syndrome 3, 615330; ?Spastic paraplegia 74, autosomal recessive to Multiple mitochondrial dysfunctions syndrome 3, OMIM:615330; ?Spastic paraplegia 74, autosomal recessive, OMIM:616451
Possible mitochondrial disorder - nuclear genes v1.60 IBA57 Arina Puzriakova Phenotypes for gene: IBA57 were changed from MULTIPLE MITOCHONDRIAL DYSFUNCTIONS SYNDROME 3, 615330 to Multiple mitochondrial dysfunctions syndrome 3, OMIM:615330; ?Spastic paraplegia 74, autosomal recessive, OMIM:616451
Undiagnosed metabolic disorders v1.499 IBA57 Arina Puzriakova Phenotypes for gene: IBA57 were changed from ?Multiple mitochondrial dysfunctions syndrome 3, 615330; ?Spastic paraplegia 74, autosomal recessive to Multiple mitochondrial dysfunctions syndrome 3, OMIM:615330; ?Spastic paraplegia 74, autosomal recessive, OMIM:616451
Childhood onset hereditary spastic paraplegia v2.113 IBA57 Arina Puzriakova Phenotypes for gene: IBA57 were changed from ?Spastic paraplegia 74, autosomal recessive, 616451 to ?Spastic paraplegia 74, autosomal recessive, OMIM:616451
Adult onset neurodegenerative disorder v2.255 IBA57 Arina Puzriakova Phenotypes for gene: IBA57 were changed from ?Spastic paraplegia 74, autosomal recessive, 616451 to ?Spastic paraplegia 74, autosomal recessive, OMIM:616451
Adult onset hereditary spastic paraplegia v1.87 IBA57 Arina Puzriakova Phenotypes for gene: IBA57 were changed from ?Spastic paraplegia 74, autosomal recessive, 616451 to ?Spastic paraplegia 74, autosomal recessive, OMIM:616451
Hereditary spastic paraplegia v1.274 IBA57 Arina Puzriakova Phenotypes for gene: IBA57 were changed from ?Spastic paraplegia 74, autosomal recessive, 616451 to ?Spastic paraplegia 74, autosomal recessive, OMIM:616451
Childhood onset hereditary spastic paraplegia v2.112 IBA57 Arina Puzriakova changed review comment from: Comment on list classification: No further evidence was emerged since initial curation and clinical review in 2019 and therefore will maintain the Amber gene rating on spasticity panels at this time.; to: Comment on list classification: No further evidence has emerged since initial curation and clinical review in 2019 and therefore will maintain the Amber gene rating on spasticity panels at this time.
Childhood onset hereditary spastic paraplegia v2.112 IBA57 Arina Puzriakova Classified gene: IBA57 as Amber List (moderate evidence)
Childhood onset hereditary spastic paraplegia v2.112 IBA57 Arina Puzriakova Added comment: Comment on list classification: No further evidence was emerged since initial curation and clinical review in 2019 and therefore will maintain the Amber gene rating on spasticity panels at this time.
Childhood onset hereditary spastic paraplegia v2.112 IBA57 Arina Puzriakova Gene: iba57 has been classified as Amber List (Moderate Evidence).
Rhabdomyolysis and metabolic muscle disorders v1.59 PHKB Sarah Leigh edited their review of gene: PHKB: Added comment: Although pathogenic variants in PHKB result in reduced levels of phosphorylase kinase in the liver and muscle, it would appear that this results in hepatomegaly and minimal effect on the muscles (PMID 9215682 & 30397902).; Changed rating: RED
Rhabdomyolysis and metabolic muscle disorders v1.59 PHKB Sarah Leigh Publications for gene: PHKB were set to 27604308; 9215682; 30397902
Rhabdomyolysis and metabolic muscle disorders v1.58 PHKB Sarah Leigh Tag Q4_21_rating tag was added to gene: PHKB.
Tag Q4_21_phenotype tag was added to gene: PHKB.
Rhabdomyolysis and metabolic muscle disorders v1.58 PHKB Sarah Leigh Publications for gene: PHKB were set to 27604308
Mosaic skin disorders - deep sequencing v1.12 BRAF Eleanor Williams Classified gene: BRAF as Amber List (moderate evidence)
Mosaic skin disorders - deep sequencing v1.12 BRAF Eleanor Williams Added comment: Comment on list classification: Promoting this gene from grey to amber but with a recommendation for GREEN rating following GMS review. More than 3 cases with tissue specific mosaic missense variants reported and a relevant skin phenotype.
Mosaic skin disorders - deep sequencing v1.12 BRAF Eleanor Williams Gene: braf has been classified as Amber List (Moderate Evidence).
Mosaic skin disorders - deep sequencing v1.11 BRAF Eleanor Williams Phenotypes for gene: BRAF were changed from Melanocytic naevus syndrome (MIM 137550); Vascular malformations; Noonan syndrome 7 (MIM 613706); LEOPARD syndrome 3 (MIM 613707); Cardio-facio-cutaneous syndrome 1 (MIM 115150) to Melanocytic naevus syndrome, OMIM:137550; Vascular malformations; Noonan syndrome 7 (MIM 613706); LEOPARD syndrome 3 , OMIM:613707; Cardio-facio-cutaneous syndrome 1, OMIM:115150
Mosaic skin disorders - deep sequencing v1.10 BRAF Eleanor Williams Publications for gene: BRAF were set to PMID: 31111470; 31891627; 29461977
Mosaic skin disorders - deep sequencing v1.9 BRAF Eleanor Williams Tag Q4_21_rating tag was added to gene: BRAF.
Mosaic skin disorders - deep sequencing v1.9 BRAF Eleanor Williams commented on gene: BRAF
Severe microcephaly v2.274 GPT2 Arina Puzriakova Classified gene: GPT2 as Amber List (moderate evidence)
Severe microcephaly v2.274 GPT2 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at then next GMS panel update.
Severe microcephaly v2.274 GPT2 Arina Puzriakova Gene: gpt2 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v2.273 GPT2 Arina Puzriakova gene: GPT2 was added
gene: GPT2 was added to Severe microcephaly. Sources: Literature
Q4_21_rating tags were added to gene: GPT2.
Mode of inheritance for gene: GPT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GPT2 were set to 25758935; 27601654; 29226631; 29882329; 31471722
Phenotypes for gene: GPT2 were set to Neurodevelopmental disorder with microcephaly and spastic paraplegia, OMIM:616281
Review for gene: GPT2 was set to GREEN
Added comment: Microcephaly is a prominent features of the neurodevelopmental disorder associated with biallelic variants in the GPT2 gene. Mostly all patients are to some degree microcephalic but at least 6 unrelated families (out of 11 total) have been reported with microcephaly of relevant severity to this panel (≥ -3SD). This gene is associated with a relevant phenotype in OMIM (OMIM:616281) but is not yet listed in G2P.
Sources: Literature
Childhood onset hereditary spastic paraplegia v2.111 GPT2 Arina Puzriakova Publications for gene: GPT2 were set to 29882329; 31471722; 27601654
Childhood onset hereditary spastic paraplegia v2.110 GPT2 Arina Puzriakova Tag Q4_21_rating tag was added to gene: GPT2.
Childhood onset hereditary spastic paraplegia v2.110 GPT2 Arina Puzriakova Classified gene: GPT2 as Amber List (moderate evidence)
Childhood onset hereditary spastic paraplegia v2.110 GPT2 Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark. There is sufficient evidence to promote this gene to Green at the next GMS panel update. Spastic paraplegia is a frequently reported sign which develops later in the course of disease but is often severe. As this is a prominent feature of the condition there is value in including GPT2 on this panel. This gene is associated with a relevant phenotype in OMIM (OMIM:616281) but is not yet listed in G2P.
Childhood onset hereditary spastic paraplegia v2.110 GPT2 Arina Puzriakova Gene: gpt2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v3.1468 GPT2 Arina Puzriakova Phenotypes for gene: GPT2 were changed from Microcephaly; Mental retardation, autosomal recessive 49, 138210; Intellectual disability; Progressive spasticity to Neurodevelopmental disorder with microcephaly and spastic paraplegia, OMIM:616281
Childhood onset hereditary spastic paraplegia v2.109 GPT2 Arina Puzriakova Phenotypes for gene: GPT2 were changed from Mental retardation, autosomal recessive 49 MIM#616281 to Neurodevelopmental disorder with microcephaly and spastic paraplegia, OMIM:616281
Skeletal dysplasia v2.156 PRKG2 Eleanor Williams Phenotypes for gene: PRKG2 were changed from Acromesomelic dysplasia to acromesomelic dysplasia, MONDO:0019696; spondylometaphyseal dysplasia, MONDO:0016763
Skeletal dysplasia v2.155 PRKG2 Eleanor Williams Publications for gene: PRKG2 were set to 33106379
Childhood onset hereditary spastic paraplegia v2.108 EXOSC3 Arina Puzriakova Classified gene: EXOSC3 as Amber List (moderate evidence)
Childhood onset hereditary spastic paraplegia v2.108 EXOSC3 Arina Puzriakova Added comment: Comment on list classification: Rating Amber as only two families have been reported to date with early-onset spastic paraplegia associated with biallelic variants in this gene. Other features included variable cognitive impairment and cerebellar atrophy but normal pons.
Childhood onset hereditary spastic paraplegia v2.108 EXOSC3 Arina Puzriakova Gene: exosc3 has been classified as Amber List (Moderate Evidence).
Intellectual disability v3.1467 ATP9A Sarah Leigh Publications for gene: ATP9A were set to 34379057; 34764295
Severe microcephaly v2.272 ATP9A Sarah Leigh Publications for gene: ATP9A were set to 34379057; 34764295
Severe microcephaly v2.271 ATP9A Sarah Leigh reviewed gene: ATP9A: Rating: AMBER; Mode of pathogenicity: None; Publications: 27626380; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.1466 EXOSC3 Arina Puzriakova Phenotypes for gene: EXOSC3 were changed from PONTOCEREBELLAR HYPOPLASIA TYPE 1 to Pontocerebellar hypoplasia, type 1B, OMIM:614678
Childhood onset dystonia, chorea or related movement disorder v1.202 EXOSC3 Arina Puzriakova Phenotypes for gene: EXOSC3 were changed from to Pontocerebellar hypoplasia, type 1B, OMIM:614678
Hereditary ataxia with onset in adulthood v2.127 EXOSC3 Arina Puzriakova Phenotypes for gene: EXOSC3 were changed from Pontocerebellar hypoplasia type 1B, 614678; Pontocerebellar hypoplasia, type 1B, 614678 to Pontocerebellar hypoplasia, type 1B, OMIM:614678
Early onset or syndromic epilepsy v2.473 EXOSC3 Arina Puzriakova Phenotypes for gene: EXOSC3 were changed from Pontocerebellar hypoplasia, type 1B, 614678 to Pontocerebellar hypoplasia, type 1B, OMIM:614678
Fetal anomalies v1.815 EXOSC3 Arina Puzriakova Phenotypes for gene: EXOSC3 were changed from PONTOCEREBELLAR HYPOPLASIA TYPE 1 to Pontocerebellar hypoplasia, type 1B, OMIM:614678
Adult onset neurodegenerative disorder v2.254 EXOSC3 Arina Puzriakova Phenotypes for gene: EXOSC3 were changed from Pontocerebellar hypoplasia, type 1B, 614678 to Pontocerebellar hypoplasia, type 1B, OMIM:614678
Cerebellar hypoplasia v1.61 EXOSC3 Arina Puzriakova Phenotypes for gene: EXOSC3 were changed from Pontocerebellar Hypoplasia type 1B; Pontocerebellar Hypoplasia; Pontocerebellar hypoplasia, type 1B, 614678 to Pontocerebellar hypoplasia, type 1B, OMIM:614678
Arthrogryposis v3.144 EXOSC3 Arina Puzriakova Phenotypes for gene: EXOSC3 were changed from Pontocerebellar hypoplasia, type 1B 614678 to Pontocerebellar hypoplasia, type 1B, OMIM:614678
Hereditary ataxia v1.280 EXOSC3 Arina Puzriakova Phenotypes for gene: EXOSC3 were changed from Pontocerebellar hypoplasia, type 1B, 614678 to Pontocerebellar hypoplasia, type 1B, OMIM:614678
Ataxia and cerebellar anomalies - narrow panel v2.276 EXOSC3 Arina Puzriakova Phenotypes for gene: EXOSC3 were changed from Pontocerebellar Hypoplasia; Pontocerebellar hypoplasia, type 1B, 614678; Pontocerebellar Hypoplasia type 1B to Pontocerebellar hypoplasia, type 1B, OMIM:614678
Intellectual disability v3.1465 ATP9A Sarah Leigh edited their review of gene: ATP9A: Added comment: Not associated with a phenotype in OMIM, Gen2Phen or MONDO. At least four variants reported in four unrelated families with a neurodevelopmental disorder (PMIDs: 34379057, 34764295). Model Atp9a−/− mice had neurobehavioural disabilities reminiscent to the behavioral patterns in the publications quoted here (PMID: 27626380).; Changed rating: GREEN; Changed publications to: 27626380
Intellectual disability v3.1465 ATP9A Sarah Leigh Classified gene: ATP9A as Amber List (moderate evidence)
Intellectual disability v3.1465 ATP9A Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Intellectual disability v3.1465 ATP9A Sarah Leigh Gene: atp9a has been classified as Amber List (Moderate Evidence).
Intellectual disability v3.1464 ATP9A Sarah Leigh Tag Q4_21_rating tag was added to gene: ATP9A.
Primary ovarian insufficiency v1.55 C14orf39 Andrey Gagunashvili reviewed gene: C14orf39: Rating: ; Mode of pathogenicity: None; Publications: 34718620; Phenotypes: Premature ovarian failure; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary ovarian insufficiency v1.55 SYCE1 Andrey Gagunashvili reviewed gene: SYCE1: Rating: ; Mode of pathogenicity: None; Publications: 34718620; Phenotypes: Premature ovarian failure; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.1464 ATP9A Sarah Leigh Publications for gene: ATP9A were set to 34379057
Severe microcephaly v2.271 ATP9A Sarah Leigh Publications for gene: ATP9A were set to 34379057
Cholestasis v1.98 MPI Ivone Leong Added comment: Comment on publications: Comment on publications: New publications added.
Cholestasis v1.98 MPI Ivone Leong Publications for gene: MPI were set to 12414827; 9585601; 10980531; 33098580; 33204592; 32905087; 32266963; 30242110
Cholestasis v1.97 MPI Ivone Leong Tag Q4_21_NHS_review tag was added to gene: MPI.
Cholestasis v1.97 LIPA Ivone Leong Added comment: Comment on publications: Comment on publications: New publications added.
Cholestasis v1.97 LIPA Ivone Leong Publications for gene: LIPA were set to 8254026; 29702543; 8617513; 7759067; 8598644; 26137452; 29731497; 23485521
Cholestasis v1.96 LIPA Ivone Leong Tag Q4_21_NHS_review tag was added to gene: LIPA.
Cholestasis v1.96 CFTR Ivone Leong changed review comment from: Comment on publications: New publicatins added.; to: Comment on publications: New publications added.
Cholestasis v1.96 CFTR Ivone Leong Added comment: Comment on publications: New publicatins added.
Cholestasis v1.96 CFTR Ivone Leong Publications for gene: CFTR were set to 21194565; 27806795; 22798282; 9934970; 26436368; 31041076
Cholestasis v1.95 CFTR Ivone Leong Publications for gene: CFTR were set to 21194565; 27806795; 22798282; 9934970
Cholestasis v1.94 CFTR Ivone Leong Tag Q4_21_NHS_review tag was added to gene: CFTR.
Cholestasis v1.94 ADK Ivone Leong Tag Q4_21_NHS_review tag was added to gene: ADK.
Cholestasis v1.94 ADK Ivone Leong Publications for gene: ADK were set to 21963049; 27500280; 26642971
White matter disorders and cerebral calcification - narrow panel v1.217 ELOVL1 Arina Puzriakova Entity copied from Hereditary spastic paraplegia - childhood onset v2.107
White matter disorders and cerebral calcification - narrow panel v1.217 ELOVL1 Arina Puzriakova gene: ELOVL1 was added
gene: ELOVL1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert list,Expert Review Amber
missense, Q4_21_rating tags were added to gene: ELOVL1.
Mode of inheritance for gene: ELOVL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ELOVL1 were set to 23689133; 29496980; 30487246; 32123819
Phenotypes for gene: ELOVL1 were set to Ichthyotic keratoderma, spasticity, hypomyelination, and dysmorphic facies, OMIM:618527
Ichthyosis and erythrokeratoderma v1.69 ELOVL1 Arina Puzriakova Entity copied from Hereditary spastic paraplegia - childhood onset v2.107
Ichthyosis and erythrokeratoderma v1.69 ELOVL1 Arina Puzriakova gene: ELOVL1 was added
gene: ELOVL1 was added to Ichthyosis and erythrokeratoderma. Sources: Expert list,Expert Review Amber
missense, Q4_21_rating tags were added to gene: ELOVL1.
Mode of inheritance for gene: ELOVL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ELOVL1 were set to 23689133; 29496980; 30487246; 32123819
Phenotypes for gene: ELOVL1 were set to Ichthyotic keratoderma, spasticity, hypomyelination, and dysmorphic facies, OMIM:618527
Childhood onset hereditary spastic paraplegia v2.107 ELOVL1 Arina Puzriakova Publications for gene: ELOVL1 were updated from 29496980; 32123819; 30487246 to 23689133; 29496980; 30487246; 32123819
Childhood onset hereditary spastic paraplegia v2.106 ELOVL1 Arina Puzriakova Classified gene: ELOVL1 as Amber List (moderate evidence)
Childhood onset hereditary spastic paraplegia v2.106 ELOVL1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark. Although only a single variant has been reported to date this was shown to arise de novo in unrelated individuals and the possibility of a founder effect was ruled out. Pathogenicity is supported by functional data including in vitro studies of the variant and complimentary animal models. Overall this is sufficient evidence to rate this gene as Green at the next GMS panel update.
Childhood onset hereditary spastic paraplegia v2.106 ELOVL1 Arina Puzriakova Gene: elovl1 has been classified as Amber List (Moderate Evidence).
Childhood onset hereditary spastic paraplegia v2.105 ELOVL1 Arina Puzriakova Tag missense tag was added to gene: ELOVL1.
Tag Q4_21_rating tag was added to gene: ELOVL1.
Childhood onset hereditary spastic paraplegia v2.105 ELOVL1 Arina Puzriakova reviewed gene: ELOVL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23689133, 29496980, 30487246, 32123819; Phenotypes: Ichthyotic keratoderma, spasticity, hypomyelination, and dysmorphic facies, OMIM:618527; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Retinal disorders v2.236 ELOVL1 Arina Puzriakova Mode of inheritance for gene: ELOVL1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Retinal disorders v2.235 ELOVL1 Arina Puzriakova Phenotypes for gene: ELOVL1 were changed from to Ichthyotic keratoderma, spasticity, hypomyelination, and dysmorphic facies, OMIM:618527
Childhood onset hereditary spastic paraplegia v2.105 ELOVL1 Arina Puzriakova Phenotypes for gene: ELOVL1 were changed from Ichthyotic keratoderma, spasticity, hypomyelination, and dysmorphic facies, MIM# 618527 to Ichthyotic keratoderma, spasticity, hypomyelination, and dysmorphic facies, OMIM:618527
Adult onset hereditary spastic paraplegia v1.86 CPT1C Arina Puzriakova Classified gene: CPT1C as Amber List (moderate evidence)
Adult onset hereditary spastic paraplegia v1.86 CPT1C Arina Puzriakova Added comment: Comment on list classification: Overall one family with confirmed adult-onset and one with childhood-onset have been reported, as well as two further unrelated cases but unfortunately without indication of age of onset. Although onset is variable, the gene-disease relationship is supported by a strong animal model, and therefore it is worth including CPT1C on both HSP panels as Green.
Adult onset hereditary spastic paraplegia v1.86 CPT1C Arina Puzriakova Gene: cpt1c has been classified as Amber List (Moderate Evidence).
Adult onset hereditary spastic paraplegia v1.85 CPT1C Arina Puzriakova Tag Q4_21_rating tag was added to gene: CPT1C.
Childhood onset hereditary spastic paraplegia v2.104 CPT1C Arina Puzriakova Classified gene: CPT1C as Green List (high evidence)
Childhood onset hereditary spastic paraplegia v2.104 CPT1C Arina Puzriakova Added comment: Comment on list classification: Overall one family with confirmed adult-onset and one with childhood-onset have been reported, as well as two further unrelated cases but unfortunately without indication of age of onset. Although onset is variable, the gene-disease relationship is supported by a strong animal model, and therefore it is worth including CPT1C on both HSP panels as Green.
Childhood onset hereditary spastic paraplegia v2.104 CPT1C Arina Puzriakova Gene: cpt1c has been classified as Green List (High Evidence).
Childhood onset hereditary spastic paraplegia v2.103 CPT1C Arina Puzriakova Publications for gene: CPT1C were set to 25751282; 30564185
Childhood onset hereditary spastic paraplegia v2.102 CPT1C Arina Puzriakova reviewed gene: CPT1C: Rating: ; Mode of pathogenicity: None; Publications: 30911584; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Pigmentary skin disorders v1.23 HCCS Ivone Leong Tag Q4_21_rating was removed from gene: HCCS.
Pigmentary skin disorders v1.23 HCCS Ivone Leong Tag Q4_21_rating tag was added to gene: HCCS.
Tag Q4_21_NHS_review tag was added to gene: HCCS.
Pigmentary skin disorders v1.23 HCCS Ivone Leong Phenotypes for gene: HCCS were changed from Linear Skin Defects with Multiple Congenital Anomalies to Linear skin defects with multiple congenital anomalies 1, OMIM:309801
Intellectual disability v3.1463 HCCS Ivone Leong Tag Q4_21_MOI tag was added to gene: HCCS.
Intellectual disability v3.1463 HCCS Ivone Leong reviewed gene: HCCS: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Adult onset hereditary spastic paraplegia v1.85 CPT1C Arina Puzriakova Phenotypes for gene: CPT1C were changed from ?Spastic paraplegia 73, autosomal dominant, 616282 to Spastic paraplegia 73, autosomal dominant, OMIM:616282
Childhood onset hereditary spastic paraplegia v2.102 CPT1C Arina Puzriakova Phenotypes for gene: CPT1C were changed from ?Spastic paraplegia 73, autosomal dominant, 616282, AD to Spastic paraplegia 73, autosomal dominant, OMIM:616282
Childhood onset hereditary spastic paraplegia v2.101 AP5Z1 Arina Puzriakova Publications for gene: AP5Z1 were set to Slabicki et al. (2010); 20613862; 24833714; 27606357
Childhood onset hereditary spastic paraplegia v2.100 AP5Z1 Arina Puzriakova reviewed gene: AP5Z1: Rating: ; Mode of pathogenicity: None; Publications: 24833714, 27606357, 33543803; Phenotypes: Spastic paraplegia 48, autosomal recessive, OMIM:613647; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Pigmentary skin disorders v1.22 DDX3X Ivone Leong Tag Q4_21_rating tag was added to gene: DDX3X.
Pigmentary skin disorders v1.22 DDX3X Ivone Leong Tag Q4_21_NHS_review tag was added to gene: DDX3X.
Pigmentary skin disorders v1.22 DDX3X Ivone Leong Classified gene: DDX3X as Amber List (moderate evidence)
Pigmentary skin disorders v1.22 DDX3X Ivone Leong Added comment: Comment on list classification: New gene added by Tom Cullup (Great Ormond Street Hospital). This gene is associated with a phenotype in OMIM and Gene2Phenotype (confirmed). There is enough evidence to support a gene-disease association. It should be noted that not all patient develops skin pigmentation anomalies; however, there are >3 unrelated cases. This gene should be rated Green at the next review.
Pigmentary skin disorders v1.22 DDX3X Ivone Leong Gene: ddx3x has been classified as Amber List (Moderate Evidence).
Intellectual disability v3.1463 AP5Z1 Arina Puzriakova Phenotypes for gene: AP5Z1 were changed from Spastic paraplegia 48, autosomal recessive 613647 to Spastic paraplegia 48, autosomal recessive, OMIM:613647
Childhood onset hereditary spastic paraplegia v2.100 AP5Z1 Arina Puzriakova Phenotypes for gene: AP5Z1 were changed from Spastic paraplegia 48, autosomal recessive, OMIM:613647 to Spastic paraplegia 48, autosomal recessive, OMIM:613647
Pigmentary skin disorders v1.21 DDX3X Ivone Leong Phenotypes for gene: DDX3X were changed from INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED, SYNDROMIC, SNIJDERS BLOK TYPE to Intellectual developmental disorder, X-linked, syndrome, Snijders Blok type, OMIM:300958
Childhood onset hereditary spastic paraplegia v2.99 AP5Z1 Arina Puzriakova Phenotypes for gene: AP5Z1 were changed from Spastic Paraplegia, Recessive; Spastic paraplegia 48, autosomal recessive to Spastic paraplegia 48, autosomal recessive, OMIM:613647
Hereditary spastic paraplegia v1.273 AP5Z1 Arina Puzriakova Phenotypes for gene: AP5Z1 were changed from Spastic Paraplegia, Recessive ; Spastic paraplegia 48, autosomal recessive to Spastic paraplegia 48, autosomal recessive, OMIM:613647
Childhood onset dystonia, chorea or related movement disorder v1.201 HPRT1 Arina Puzriakova Tag Q4_21_expert_review tag was added to gene: HPRT1.
Tag Q4_21_rating tag was added to gene: HPRT1.
Childhood onset dystonia, chorea or related movement disorder v1.201 HPRT1 Arina Puzriakova commented on gene: HPRT1
Childhood onset dystonia, chorea or related movement disorder v1.201 HPRT1 Arina Puzriakova Publications for gene: HPRT1 were set to
Early onset dystonia v1.98 HPRT1 Arina Puzriakova Mode of inheritance for gene: HPRT1 was changed from to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Adult onset neurodegenerative disorder v2.253 HPRT1 Arina Puzriakova Mode of inheritance for gene: HPRT1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Adult onset neurodegenerative disorder v2.252 HPRT1 Arina Puzriakova Phenotypes for gene: HPRT1 were changed from Dystonia to Lesch-Nyhan syndrome, OMIM:300322
Early onset dystonia v1.97 HPRT1 Arina Puzriakova Phenotypes for gene: HPRT1 were changed from Dystonia to Lesch-Nyhan syndrome, OMIM:300322; Dystonia
Childhood onset dystonia, chorea or related movement disorder v1.200 HPRT1 Arina Puzriakova Phenotypes for gene: HPRT1 were changed from Lesch-Nyhan syndrome, 300322 to Lesch-Nyhan syndrome, OMIM:300322; Dystonia
Adult onset dystonia, chorea or related movement disorder v1.158 HPRT1 Arina Puzriakova Phenotypes for gene: HPRT1 were changed from Lesch-Nyhan syndrome, 300322; Dystonia to Lesch-Nyhan syndrome, OMIM:300322; Dystonia
Intellectual disability v3.1462 HPRT1 Arina Puzriakova Phenotypes for gene: HPRT1 were changed from Lesch-Nyhan syndrome, 300322HPRT-related gout, 300323; GOUT HPRT-RELATED (GOUT-HPRT) to Lesch-Nyhan syndrome, OMIM:300322
Early onset or syndromic epilepsy v2.472 HPRT1 Arina Puzriakova Mode of inheritance for gene: HPRT1 was changed from to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Early onset or syndromic epilepsy v2.471 HPRT1 Arina Puzriakova Phenotypes for gene: HPRT1 were changed from to Lesch-Nyhan syndrome, OMIM:300322
Fetal anomalies v1.814 HPRT1 Arina Puzriakova Phenotypes for gene: HPRT1 were changed from LESCH-NYHAN SYNDROME; GOUT HPRT-RELATED to Hyperuricemia, HRPT-related, OMIM:300323; Lesch-Nyhan syndrome, OMIM:300322
Likely inborn error of metabolism v2.200 HPRT1 Arina Puzriakova Phenotypes for gene: HPRT1 were changed from HPRT-related gout to Hyperuricemia, HRPT-related, OMIM:300323; Lesch-Nyhan syndrome, OMIM:300322
Nephrocalcinosis or nephrolithiasis v2.25 HPRT1 Arina Puzriakova Phenotypes for gene: HPRT1 were changed from Lesch-Nyhan syndrome, 300322 to Hyperuricemia, HRPT-related, OMIM:300323; Lesch-Nyhan syndrome, OMIM:300322
Undiagnosed metabolic disorders v1.498 HPRT1 Arina Puzriakova Phenotypes for gene: HPRT1 were changed from HPRT-related gout 300323; Lesch-Nyhan syndrome 300322 to Hyperuricemia, HRPT-related, OMIM:300323; Lesch-Nyhan syndrome, OMIM:300322
Pigmentary skin disorders v1.20 COX7B Ivone Leong Classified gene: COX7B as Amber List (moderate evidence)
Pigmentary skin disorders v1.20 COX7B Ivone Leong Added comment: Comment on list classification: New gene added by Tom Cullup (Great Ormond Street Hospital). This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype (confirmed). There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Pigmentary skin disorders v1.20 COX7B Ivone Leong Gene: cox7b has been classified as Amber List (Moderate Evidence).
Pigmentary skin disorders v1.19 COX7B Ivone Leong Tag Q4_21_rating tag was added to gene: COX7B.
Tag Q4_21_NHS_review tag was added to gene: COX7B.
Structural eye disease v1.92 COX7B Ivone Leong Added comment: Comment on mode of inheritance: MOI 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)" as the latter is the correct MOI.
Structural eye disease v1.92 COX7B Ivone Leong Mode of inheritance for gene: COX7B 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)
Severe early-onset obesity v2.45 KIDINS220 Arina Puzriakova Classified gene: KIDINS220 as Amber List (moderate evidence)
Severe early-onset obesity v2.45 KIDINS220 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update.
Severe early-onset obesity v2.45 KIDINS220 Arina Puzriakova Gene: kidins220 has been classified as Amber List (Moderate Evidence).
Severe early-onset obesity v2.44 KIDINS220 Arina Puzriakova gene: KIDINS220 was added
gene: KIDINS220 was added to Severe early-onset obesity. Sources: Literature
Q4_21_rating tags were added to gene: KIDINS220.
Mode of inheritance for gene: KIDINS220 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KIDINS220 were set to 27005418; 29667355; 33763417
Phenotypes for gene: KIDINS220 were set to Spastic paraplegia, intellectual disability, nystagmus, and obesity, OMIM:617296
Review for gene: KIDINS220 was set to GREEN
Added comment: Seven individuals from five unrelated families have been reported with spastic paraplegia, intellectual disability, nystagmus, and obesity (SINO) syndrome (OMIM:617296) associated with monoallelic variants in the KIDINS220 gene. Phenotypes include early-onset obesity and, where indicated, this translates to a weight above the 99th percentile in infancy.
Sources: Literature
Intellectual disability v3.1461 KIDINS220 Arina Puzriakova Phenotypes for gene: KIDINS220 were changed from Spastic paraplegia, intellectual disability, nystagmus, and obesity, 617296 to Spastic paraplegia, intellectual disability, nystagmus, and obesity OMIM:617296
Intellectual disability v3.1460 KIDINS220 Arina Puzriakova Publications for gene: KIDINS220 were set to 27005418; 29667355
Adult onset hereditary spastic paraplegia v1.84 KIDINS220 Arina Puzriakova Phenotypes for gene: KIDINS220 were changed from Spastic paraplegia, intellectual disability, nystagmus, and obesity, autosomal dominant, 617296 to Spastic paraplegia, intellectual disability, nystagmus, and obesity, OMIM:617296
Childhood onset hereditary spastic paraplegia v2.98 KIDINS220 Arina Puzriakova Phenotypes for gene: KIDINS220 were changed from Spastic paraplegia, intellectual disability, nystagmus, and obesity, 617296 to Spastic paraplegia, intellectual disability, nystagmus, and obesity, OMIM:617296
Adult onset neurodegenerative disorder v2.251 KIDINS220 Arina Puzriakova Phenotypes for gene: KIDINS220 were changed from Spastic paraplegia, intellectual disability, nystagmus, and obesity 617296 to Spastic paraplegia, intellectual disability, nystagmus, and obesity, OMIM:617296
Fetal anomalies v1.813 KIDINS220 Arina Puzriakova Added comment: Comment on phenotypes: Added relevant phenotype now listed in OMIM (MIM# 619501)
Fetal anomalies v1.813 KIDINS220 Arina Puzriakova Phenotypes for gene: KIDINS220 were changed from Spastic paraplegia, intellectual disability, nystagmus, and obesity OMIM:617296; spastic paraplegia, intellectual disability, nystagmus, and obesity MONDO:0015007; cerebral ventriculomegaly; limb contractures to Ventriculomegaly and arthrogryposis, OMIM:619501
Hydrocephalus v2.125 KIDINS220 Arina Puzriakova Added comment: Comment on phenotypes: Added relevant phenotype now listed in OMIM (MIM# 619501)
Hydrocephalus v2.125 KIDINS220 Arina Puzriakova Phenotypes for gene: KIDINS220 were changed from brain ventriculomegaly and limb contractures to Ventriculomegaly and arthrogryposis, OMIM:619501
Arthrogryposis v3.143 KIDINS220 Arina Puzriakova Added comment: Comment on phenotypes: Added relevant phenotype now listed in OMIM (MIM# 619501)
Arthrogryposis v3.143 KIDINS220 Arina Puzriakova Phenotypes for gene: KIDINS220 were changed from brain ventriculomegaly and limb contractures to Ventriculomegaly and arthrogryposis, OMIM:619501
Hereditary spastic paraplegia v1.272 KIDINS220 Sarah Leigh Added comment: Comment on mode of pathogenicity: Personal communication from Dmitrijs Rots (RadboudUMC). Prompted by the occurrence of a KIDINS220 nonsense variant in the middle of the gene, in a family without spastic paraplegia (HSP) or other features; an in-depth analysis of KIDINS220 variants was performed. It would appear that KIDINS220 gene is tolerant of LOF variants (nonsense, frameshift) in gnomAD population (hence pLI~ 0, in the PanelApp review by Dmitrijs Rots (RadboudUMC), 4 Nov 2021). This was unexpected, as KIDINS220-associated-HSP presents in childhood, so it would appear that haploinsufficiency is unlikely as the mechanism. In addition, there were nonsense/frameshift HSP-associated variants in KIDINS220, but they were located in the last two exons of the gene and so likely to escape nonsense mediated decay. Therefore, it is proposed that rather a LOF mechanism a dominant negative effect may be responsible, however, further cases need to be identified to confirm this.
Hereditary spastic paraplegia v1.272 KIDINS220 Sarah Leigh Mode of pathogenicity for gene: KIDINS220 was changed from None to None
Xeroderma pigmentosum, Trichothiodystrophy or Cockayne syndrome v2.25 MARS Arina Puzriakova commented on gene: MARS
Xeroderma pigmentosum, Trichothiodystrophy or Cockayne syndrome v2.25 MARS Arina Puzriakova Tag watchlist tag was added to gene: MARS.
Xeroderma pigmentosum, Trichothiodystrophy or Cockayne syndrome v2.25 AARS Arina Puzriakova changed review comment from: Gene was reassessed in view of the recent Green review by Alan Lehmann. An additional case is necessary to allow corroboration of this gene-disease association (added 'watchlist' tag). At present, CARS1 is the only aminoacyl tRNA synthetase gene for which sufficient evidence has been reported to warrant a Green rating on this panel.; to: Gene was reassessed in view of the recent Green review by Alan Lehmann (5 Nov 2021). An additional case is necessary to allow corroboration of this gene-disease association (added 'watchlist' tag). At present, CARS1 is the only aminoacyl tRNA synthetase gene for which sufficient evidence has been reported to warrant a Green rating on this panel.
Xeroderma pigmentosum, Trichothiodystrophy or Cockayne syndrome v2.25 AARS Arina Puzriakova commented on gene: AARS
Xeroderma pigmentosum, Trichothiodystrophy or Cockayne syndrome v2.25 AARS Arina Puzriakova Tag watchlist tag was added to gene: AARS.
Xeroderma pigmentosum, Trichothiodystrophy or Cockayne syndrome v2.25 TARS Arina Puzriakova Tag watchlist tag was added to gene: TARS.
Xeroderma pigmentosum, Trichothiodystrophy or Cockayne syndrome v2.25 TARS Arina Puzriakova Classified gene: TARS as Amber List (moderate evidence)
Xeroderma pigmentosum, Trichothiodystrophy or Cockayne syndrome v2.25 TARS Arina Puzriakova Added comment: Comment on list classification: Adding this gene as Amber as currently only two unrelated individuals have been reported with variants and trichothiodystrophy (PMID: 31374204). Familial segregation was not reported in either case. Functional studies demonstrate the variants exert a loss-of-function effect but an additional case would help corroborate this gene-disease association (added 'watchlist' tag). At present, CARS1 is the only aminoacyl tRNA synthetase gene for which sufficient evidence has been reported to warrant a Green rating on this panel.
Xeroderma pigmentosum, Trichothiodystrophy or Cockayne syndrome v2.25 TARS Arina Puzriakova Gene: tars has been classified as Amber List (Moderate Evidence).
Xeroderma pigmentosum, Trichothiodystrophy or Cockayne syndrome v2.24 TARS Arina Puzriakova Mode of pathogenicity for gene: TARS was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to None
Xeroderma pigmentosum, Trichothiodystrophy or Cockayne syndrome v2.23 TARS Arina Puzriakova Publications for gene: TARS were set to PMID 31374204
Xeroderma pigmentosum, Trichothiodystrophy or Cockayne syndrome v2.22 TARS Arina Puzriakova Phenotypes for gene: TARS were changed from Trichothiodystrophy 7, nonphotosensitive to Trichothiodystrophy 7, nonphotosensitive, OMIM:618546
DDG2P v2.53 TARS Arina Puzriakova Tag new-gene-name tag was added to gene: TARS.
Xeroderma pigmentosum, Trichothiodystrophy or Cockayne syndrome v2.21 TARS Arina Puzriakova Tag new-gene-name tag was added to gene: TARS.
Xeroderma pigmentosum, Trichothiodystrophy or Cockayne syndrome v2.21 CARS Arina Puzriakova Publications for gene: CARS were set to PMID 30824121
Xeroderma pigmentosum, Trichothiodystrophy or Cockayne syndrome v2.20 CARS Arina Puzriakova Classified gene: CARS as Amber List (moderate evidence)
Xeroderma pigmentosum, Trichothiodystrophy or Cockayne syndrome v2.20 CARS Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update. At least four individuals from three unrelated families harbouring different biallelic variants in the CARS gene. Clinical presentation includes ID and brittle hair and nails, features which overlap with the trichothiodystrophy component of this panel. Some supportive functional studies included.
Xeroderma pigmentosum, Trichothiodystrophy or Cockayne syndrome v2.20 CARS Arina Puzriakova Gene: cars has been classified as Amber List (Moderate Evidence).
Xeroderma pigmentosum, Trichothiodystrophy or Cockayne syndrome v2.19 CARS Arina Puzriakova Tag Q4_21_rating tag was added to gene: CARS.
Xeroderma pigmentosum, Trichothiodystrophy or Cockayne syndrome v2.19 CARS Arina Puzriakova Tag new-gene-name tag was added to gene: CARS.
Pigmentary skin disorders v1.19 COX7B Ivone Leong Phenotypes for gene: COX7B were changed from Linear Skin Defects with Multiple Congenital Anomalies to Linear skin defects with multiple congenital anomalies 2, OMIM:300887
Intellectual disability v3.1459 CARS Arina Puzriakova Phenotypes for gene: CARS were changed from Brittle hair; Fragile nails; Microcephaly; Neurodevelopmental delay; Microcephaly, developmental delay, and brittle hair syndrome MIM#618891 to Microcephaly, developmental delay, and brittle hair syndrome, OMIM:618891
Xeroderma pigmentosum, Trichothiodystrophy or Cockayne syndrome v2.19 CARS Arina Puzriakova Phenotypes for gene: CARS were changed from Microcephaly; Developmental Delay; Brittle Hair to Microcephaly, developmental delay, and brittle hair syndrome, OMIM:618891
Rare multisystem ciliopathy disorders v1.153 TMEM218 Ivone Leong Classified gene: TMEM218 as Green List (high evidence)
Rare multisystem ciliopathy disorders v1.153 TMEM218 Ivone Leong Gene: tmem218 has been classified as Green List (High Evidence).
Rare multisystem ciliopathy disorders v1.152 TMEM218 Ivone Leong changed review comment from: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in OMIM but not in Gene2Phenotype. There is sufficient evidence to support a gene-disease association. This gene should be rated Green at the next review.; to: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in OMIM but not in Gene2Phenotype. There is sufficient evidence to support a gene-disease association. This gene has been rated Green.
Rare multisystem ciliopathy disorders v1.152 TMEM218 Ivone Leong Tag Q4_21_rating was removed from gene: TMEM218.
Tag Q4_21_NHS_review was removed from gene: TMEM218.
Ophthalmological ciliopathies v1.26 TMEM218 Ivone Leong Entity copied from Neurological ciliopathies v1.24
Ophthalmological ciliopathies v1.26 TMEM218 Ivone Leong gene: TMEM218 was added
gene: TMEM218 was added to Ophthalmological ciliopathies. Sources: Literature,Expert Review Amber
Q4_21_rating, Q4_21_NHS_review tags were added to gene: TMEM218.
Mode of inheritance for gene: TMEM218 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM218 were set to 25161209; 33791682
Phenotypes for gene: TMEM218 were set to Joubert syndrome 39, OMIM:619562
Rare multisystem ciliopathy disorders v1.152 TMEM218 Ivone Leong Entity copied from Neurological ciliopathies v1.24
Rare multisystem ciliopathy disorders v1.152 TMEM218 Ivone Leong gene: TMEM218 was added
gene: TMEM218 was added to Rare multisystem ciliopathy disorders. Sources: Literature,Expert Review Amber
Q4_21_rating, Q4_21_NHS_review tags were added to gene: TMEM218.
Mode of inheritance for gene: TMEM218 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM218 were set to 25161209; 33791682
Phenotypes for gene: TMEM218 were set to Joubert syndrome 39, OMIM:619562
Retinal disorders v2.234 TMEM218 Ivone Leong Entity copied from Neurological ciliopathies v1.24
Retinal disorders v2.234 TMEM218 Ivone Leong gene: TMEM218 was added
gene: TMEM218 was added to Retinal disorders. Sources: Literature,Expert Review Amber
Q4_21_rating, Q4_21_NHS_review tags were added to gene: TMEM218.
Mode of inheritance for gene: TMEM218 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM218 were set to 25161209; 33791682
Phenotypes for gene: TMEM218 were set to Joubert syndrome 39, OMIM:619562
Neurological ciliopathies v1.24 TMEM218 Ivone Leong Classified gene: TMEM218 as Amber List (moderate evidence)
Neurological ciliopathies v1.24 TMEM218 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in OMIM but not in Gene2Phenotype. There is sufficient evidence to support a gene-disease association. This gene should be rated Green at the next review.
Neurological ciliopathies v1.24 TMEM218 Ivone Leong Gene: tmem218 has been classified as Amber List (Moderate Evidence).
Neurological ciliopathies v1.23 TMEM218 Ivone Leong Tag Q4_21_NHS_review tag was added to gene: TMEM218.
Neurological ciliopathies v1.23 TMEM218 Ivone Leong Tag Q4_21_rating tag was added to gene: TMEM218.
Intellectual disability v3.1458 GABRD Arina Puzriakova Classified gene: GABRD as Amber List (moderate evidence)
Intellectual disability v3.1458 GABRD Arina Puzriakova Added comment: Comment on list classification: There are sufficient unrelated cases to rate this gene as Green at the next GMS panel update. Although all patients presented epilepsy, it is not clear from the case reports whether cognitive impairment was secondary or independent of seizures. For this reason I think its worth including GABRD on this panel as it is plausible that DD may be evident prior to seizure onset (ranging from 4 months to 4 years in report)
Intellectual disability v3.1458 GABRD Arina Puzriakova Gene: gabrd has been classified as Amber List (Moderate Evidence).
Intellectual disability v3.1457 GABRD Arina Puzriakova gene: GABRD was added
gene: GABRD was added to Intellectual disability. Sources: Literature
Q4_21_rating tags were added to gene: GABRD.
Mode of inheritance for gene: GABRD was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GABRD were set to 34633442
Phenotypes for gene: GABRD were set to {Epilepsy, idiopathic generalized, 10}, OMIM:613060; {Epilepsy, juvenile myoclonic, susceptibility to}, OMIM:613060
Mode of pathogenicity for gene: GABRD was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: GABRD was set to GREEN
Added comment: Ahring et al., 2021 (PMID: 34633442) reports on at least 3 unrelated individuals with de novo variants and one family with 3 affected individuals harbouring an inherited variant in the GABRD gene. All variants exerted a gain-of-function effect and all carriers displayed a homogenous phenotype of generalised epilepsy (median age of onset 10.5 months, medically refractory in 5/6) and various degrees of learning difficulties or ID (learning difficulties in 1, mild ID in 2, mild to moderate ID in 1, and severe to profound ID in 2).

NB. A further three individuals were excluded from phenotypic analysis as their variants (p.M87L and p.V442I) did not show any detectable functional changes. There was also another patient with a loss-of-function variant but they displayed ASD, normal intelligence and no seizure history.
Sources: Literature
Neurological ciliopathies v1.23 TMEM218 Ivone Leong Phenotypes for gene: TMEM218 were changed from Joubert syndrome; retinal dystrophy; polycystic kidneys; occipital encephalocele to Joubert syndrome 39, OMIM:619562
Neurological ciliopathies v1.22 TMEM218 Ivone Leong Publications for gene: TMEM218 were set to 25161209; https://doi.org/10.1016/j.xhgg.2020.100016
Early onset or syndromic epilepsy v2.470 GABRD Arina Puzriakova Tag Q4_21_rating tag was added to gene: GABRD.
Early onset or syndromic epilepsy v2.470 GABRD Arina Puzriakova Classified gene: GABRD as Amber List (moderate evidence)
Early onset or syndromic epilepsy v2.470 GABRD Arina Puzriakova Added comment: Comment on list classification: Upgraded from Red to Amber but this gene should now be promoted to Green at the next GMS panel update.

New evidence identified by Helen Lord (OUH NHS) highlights at least 3 unrelated individuals with de novo variants and one family with 3 affected individuals harbouring an inherited variant in the GABRD gene (PMID: 34633442). All variants exerted a gain-of-function effect and all carriers displayed a homogenous phenotype of generalised epilepsy (median age of onset 10.5 months, medically refractory in 5/6) and various degrees of learning difficulties or ID.
Early onset or syndromic epilepsy v2.470 GABRD Arina Puzriakova Gene: gabrd has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v2.469 GABRD Arina Puzriakova Mode of pathogenicity for gene: GABRD was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Early onset or syndromic epilepsy v2.468 GABRD Arina Puzriakova Publications for gene: GABRD were set to 29785705
Early onset or syndromic epilepsy v2.467 GABRD Arina Puzriakova Phenotypes for gene: GABRD were changed from {Epilepsy, idiopathic generalized, 10} 613060; {Epilepsy, juvenile myoclonic, susceptibility to} 613060; {Epilepsy, generalized, with febrile seizures plus, type 5, susceptibility to} 613060 to {Epilepsy, idiopathic generalized, 10}, OMIM:613060; {Epilepsy, juvenile myoclonic, susceptibility to}, OMIM:613060; {Generalized epilepsy with febrile seizures plus, type 5, susceptibility to}, OMIM:613060
Early onset or syndromic epilepsy v2.466 GABRD Arina Puzriakova Tag Q4_21_NHS_review tag was added to gene: GABRD.
Ichthyosis and erythrokeratoderma v1.68 ASPRV1 Arina Puzriakova Tag Q4_21_NHS_review tag was added to gene: ASPRV1.
Skeletal dysplasia v2.154 PRKG2 Alistair Pagnamenta reviewed gene: PRKG2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34782440, 33106379, 34680883; Phenotypes: spondylometaphyseal, acromesomelic dysplasia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Inherited polyposis and early onset colorectal cancer - germline testing v1.26 AXIN2 Arina Puzriakova Classified gene: AXIN2 as Amber List (moderate evidence)
Inherited polyposis and early onset colorectal cancer - germline testing v1.26 AXIN2 Arina Puzriakova Gene: axin2 has been classified as Amber List (Moderate Evidence).
Inherited polyposis and early onset colorectal cancer - germline testing v1.25 AXIN2 Arina Puzriakova gene: AXIN2 was added
gene: AXIN2 was added to Inherited polyposis. Sources: Literature
Q4_21_rating tags were added to gene: AXIN2.
Mode of inheritance for gene: AXIN2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AXIN2 were set to 15042511; 21416598; 30671715; 32807118; 34637023
Phenotypes for gene: AXIN2 were set to Oligodontia-colorectal cancer syndrome, OMIM:608615
Review for gene: AXIN2 was set to GREEN
Added comment: AXIN2 is associated with a relevant phenotype in OMIM (MIM# 608615) but is not yet listed in Gen2Phen. At least 6 unrelated families reported with colorectal cancer and/or colon polyps due to monoallelic variants in the AXIN2. This is often concurrent with oligodontia. Sufficient cases to rate as Green on this panel.
Sources: Literature
Ectodermal dysplasia v1.30 AXIN2 Arina Puzriakova Publications for gene: AXIN2 were set to 15042511
Ectodermal dysplasia v1.29 AXIN2 Arina Puzriakova Tag Q4_21_expert_review tag was added to gene: AXIN2.
Ectodermal dysplasia v1.29 AXIN2 Arina Puzriakova Classified gene: AXIN2 as Amber List (moderate evidence)
Ectodermal dysplasia v1.29 AXIN2 Arina Puzriakova Added comment: Comment on list classification: New gene added by Tom Cullup (GOSH). Variants are associated with tooth agenesis (PMID: 15042511; 21626677; 30671715; 32807118), often additionally with colon polyps and colorectal cancer. Two families have been identified with concurrent ectodermal dysplasia including sparse or brittle hair and/or eyebrows and dry skin (PMID: 21416598; 34637023).

Given that in most families ectodermal features are isolated to oligodontia only, this gene will be flagged for GMS review to determine whether there is enough evidence to rate AXIN2 as Green on this panel.
Ectodermal dysplasia v1.29 AXIN2 Arina Puzriakova Gene: axin2 has been classified as Amber List (Moderate Evidence).
Ectodermal dysplasia v1.28 AXIN2 Arina Puzriakova Tag Q4_21_NHS_review tag was added to gene: AXIN2.
Cutaneous photosensitivity with a likely genetic cause v1.8 ANAPC1 Arina Puzriakova Tag Q4_21_NHS_review tag was added to gene: ANAPC1.
Ectodermal dysplasia v1.28 ANAPC1 Arina Puzriakova Tag Q4_21_NHS_review tag was added to gene: ANAPC1.
Ectodermal dysplasia v1.28 AXIN2 Arina Puzriakova Phenotypes for gene: AXIN2 were changed from OLIGODONTIA-COLORECTAL CANCER SYNDROME to Oligodontia-colorectal cancer syndrome, OMIM:608615
Rare syndromic craniosynostosis or isolated multisuture synostosis v2.60 AXIN2 Arina Puzriakova Mode of inheritance for gene: AXIN2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Rare syndromic craniosynostosis or isolated multisuture synostosis v2.59 AXIN2 Arina Puzriakova Phenotypes for gene: AXIN2 were changed from Oligodontia-colorectal cancer syndrome 604025 to Oligodontia-colorectal cancer syndrome, OMIM:608615
Cholestasis v1.93 MPI Miranda Durkie reviewed gene: MPI: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33413482, PMID: 28108845; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cholestasis v1.93 LIPA Miranda Durkie reviewed gene: LIPA: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 26137452, PMID: 33964214; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cholestasis v1.93 CFTR Miranda Durkie reviewed gene: CFTR: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 22798282, PMID: 27806795, PMID: 26436368, PMID: 31041076; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cholestasis v1.93 ADK Miranda Durkie reviewed gene: ADK: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33309011, PMID: 27500280, PMID: 21963049; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v2.466 CLPB Arina Puzriakova Publications for gene: CLPB were set to 26916670; 25597510; 25597511
Early onset or syndromic epilepsy v2.465 CLPB Arina Puzriakova Tag Q4_21_expert_review tag was added to gene: CLPB.
Early onset or syndromic epilepsy v2.465 CLPB Arina Puzriakova reviewed gene: CLPB: Rating: ; Mode of pathogenicity: None; Publications: 25597510, 25597511, 26916670, 28687938, 34140661; Phenotypes: 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropenia, OMIM:616271; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Childhood onset dystonia, chorea or related movement disorder v1.199 CLPB Arina Puzriakova Tag Q4_21_MOI tag was added to gene: CLPB.
Childhood onset dystonia, chorea or related movement disorder v1.199 CLPB Arina Puzriakova Publications for gene: CLPB were set to
Childhood onset dystonia, chorea or related movement disorder v1.198 CLPB Arina Puzriakova Added comment: Comment on mode of inheritance: MOI should be updated from 'Biallelic' to 'Both mono- and biallelic' at the next GMS update.

Association between biallelic variants and disease is well established, with at least 7 affected individuals reported with a movement disorder. Recently, Wortmann et al. 2021 (PMID: 34140661) published six unrelated individuals with one of four different de novo monoallelic missense variants in CLPB. The phenotype strongly overlapped with that observed in the recessive disease. Three individuals were nonambulatory and one was ambulatory but with a wide based gait and not able to run or jump. Some functional studies of heterozygous variants were performed.
Childhood onset dystonia, chorea or related movement disorder v1.198 CLPB Arina Puzriakova Mode of inheritance for gene: CLPB was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.812 CLPB Arina Puzriakova Tag Q4_21_expert_review tag was added to gene: CLPB.
Tag Q4_21_MOI tag was added to gene: CLPB.
Fetal anomalies v1.812 CLPB Arina Puzriakova Publications for gene: CLPB were set to
Fetal anomalies v1.811 CLPB Arina Puzriakova Added comment: Comment on mode of inheritance: Association between biallelic variants and disease is well established, with more than 35 affected individuals reported. Recently, Wortmann et al. 2021 (PMID: 34140661) published six unrelated individuals with one of four different de novo monoallelic missense variants in CLPB. The phenotype strongly overlapped with that observed in the recessive disease. No prenatal findings were specifically mentioned but given the otherwise comparable clinical presentations, monoallelic inheritance may also be of relevance to this panel. Therefore, will flag this for further GMS review.
Fetal anomalies v1.811 CLPB Arina Puzriakova Mode of inheritance for gene: CLPB was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v2.62 CLPB Arina Puzriakova Tag Q4_21_MOI tag was added to gene: CLPB.
Possible mitochondrial disorder - nuclear genes v1.59 CLPB Arina Puzriakova Tag Q4_21_MOI tag was added to gene: CLPB.
Mitochondrial disorders v2.62 CLPB Arina Puzriakova Publications for gene: CLPB were set to PMID: 25595726; PMID: 25597510; PMID: 25597511; PMID: 25650066
Possible mitochondrial disorder - nuclear genes v1.59 CLPB Arina Puzriakova Publications for gene: CLPB were set to
Mitochondrial disorders v2.61 CLPB Arina Puzriakova Added comment: Comment on mode of inheritance: MOI should be updated from 'Biallelic' to 'Both mono- and biallelic' at the next GMS update.

Association between biallelic variants and disease is well established, with more than 35 affected individuals reported. Recently, Wortmann et al. 2021 (PMID: 34140661) published six unrelated individuals with one of four different de novo monoallelic missense variants in CLPB. The phenotype strongly overlapped with that observed in the recessive disease including 3-MGA-uria in all cases. Some functional studies were performed which demonstrated changes in the mitochondrial proteome in patient fibroblasts.
Mitochondrial disorders v2.61 CLPB Arina Puzriakova Mode of inheritance for gene: CLPB was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Possible mitochondrial disorder - nuclear genes v1.58 CLPB Arina Puzriakova Added comment: Comment on mode of inheritance: MOI should be updated from 'Biallelic' to 'Both mono- and biallelic' at the next GMS update.

Association between biallelic variants and disease is well established, with more than 35 affected individuals reported. Recently, Wortmann et al. 2021 (PMID: 34140661) published six unrelated individuals with one of four different de novo monoallelic missense variants in CLPB. The phenotype strongly overlapped with that observed in the recessive disease including 3-MGA-uria in all cases. Some functional studies were performed which demonstrated changes in the mitochondrial proteome in patient fibroblasts.
Possible mitochondrial disorder - nuclear genes v1.58 CLPB Arina Puzriakova Mode of inheritance for gene: CLPB was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v2.496 CLPB Arina Puzriakova changed review comment from: Comment on mode of inheritance: MOI should be updated from 'Biallelic' to 'Both mono- and biallelic' at the next GMS update.

Association between biallelic variants and disease is well established, with more than >10 affected individuals reported. Recently, Wortmann et al. 2021 (PMID: 34140661) published six unrelated individuals with one of four different de novo monoallelic missense variants in CLPB. The phenotype strongly overlapped with that observed in the recessive disease, including moderate to severe congenital/early-onset neutropenia in 5/6 cases. Some functional studies of heterozygous variants were performed.; to: Comment on mode of inheritance: MOI should be updated from 'Biallelic' to 'Both mono- and biallelic' at the next GMS update.

Association between biallelic variants and disease is well established, with more than 10 affected individuals reported. Recently, Wortmann et al. 2021 (PMID: 34140661) published six unrelated individuals with one of four different de novo monoallelic missense variants in CLPB. The phenotype strongly overlapped with that observed in the recessive disease, including moderate to severe congenital/early-onset neutropenia in 5/6 cases. Some functional studies of heterozygous variants were performed.
Primary immunodeficiency or monogenic inflammatory bowel disease v2.496 CLPB Arina Puzriakova Tag Q4_21_MOI tag was added to gene: CLPB.
Primary immunodeficiency or monogenic inflammatory bowel disease v2.496 CLPB Arina Puzriakova Publications for gene: CLPB were set to 27891836; 25597510; 28687938; 25597511; 25650066; 26916670
Primary immunodeficiency or monogenic inflammatory bowel disease v2.495 CLPB Arina Puzriakova Added comment: Comment on mode of inheritance: MOI should be updated from 'Biallelic' to 'Both mono- and biallelic' at the next GMS update.

Association between biallelic variants and disease is well established, with more than >10 affected individuals reported. Recently, Wortmann et al. 2021 (PMID: 34140661) published six unrelated individuals with one of four different de novo monoallelic missense variants in CLPB. The phenotype strongly overlapped with that observed in the recessive disease, including moderate to severe congenital/early-onset neutropenia in 5/6 cases. Some functional studies of heterozygous variants were performed.
Primary immunodeficiency or monogenic inflammatory bowel disease v2.495 CLPB Arina Puzriakova Mode of inheritance for gene: CLPB was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.1456 CLPB Arina Puzriakova Publications for gene: CLPB were set to 25597510
Intellectual disability v3.1455 CLPB Arina Puzriakova Added comment: Comment on mode of inheritance: MOI should be updated from 'Biallelic' to 'Both mono- and biallelic' at the next GMS update.

Association between biallelic variants and disease is well established, with more than 35 affected individuals reported. Recently, Wortmann et al. 2021 (PMID: 34140661) published six unrelated individuals with one of four different de novo monoallelic missense variants in CLPB. The phenotype strongly overlapped with that observed in the recessive disease, including mild to severe DD/ID in all cases. Some functional studies of heterozygous variants were performed.
Intellectual disability v3.1455 CLPB Arina Puzriakova Mode of inheritance for gene: CLPB was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.1454 CLPB Arina Puzriakova Tag Q4_21_MOI tag was added to gene: CLPB.
Cytopenia - NOT Fanconi anaemia v1.47 CLPB Arina Puzriakova Tag Q4_21_rating tag was added to gene: CLPB.
Cytopenia - NOT Fanconi anaemia v1.47 CLPB Arina Puzriakova Classified gene: CLPB as Amber List (moderate evidence)
Cytopenia - NOT Fanconi anaemia v1.47 CLPB Arina Puzriakova Added comment: Comment on list classification: Upgraded from Red to Amber but should be made Green at the next GMS panel update.

Neutropenia is often reported and can be a severe and early feature, sometimes present from birth. Neutropenia was observed in at least 11 biallelic cases and 5 monoallelic cases which is sufficient for a Green rating under the MOI 'Both mono- and biallelic'
Cytopenia - NOT Fanconi anaemia v1.47 CLPB Arina Puzriakova Gene: clpb has been classified as Amber List (Moderate Evidence).
Cytopenia - NOT Fanconi anaemia v1.46 CLPB Arina Puzriakova Publications for gene: CLPB were set to
Cytopenia - NOT Fanconi anaemia v1.45 CLPB Arina Puzriakova Mode of inheritance for gene: CLPB was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Undiagnosed metabolic disorders v1.497 CLPB Arina Puzriakova Added comment: Comment on mode of inheritance: Updated MOI from 'Biallelic' to 'Both mono- and biallelic'.

Association between biallelic variants and disease is well established, with more than 35 affected individuals reported. Recently, six unrelated individuals with de novo monoallelic missense variants in CLPB were identified (PMID: 34140661). The phenotype strongly overlapped with that observed in the recessive disease, including 3-MGA-uria in all cases.
Undiagnosed metabolic disorders v1.497 CLPB Arina Puzriakova Mode of inheritance for gene: CLPB was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Undiagnosed metabolic disorders v1.496 CLPB Arina Puzriakova Publications for gene: CLPB were set to 25595726; 25597510; 25597511; 25650066
Likely inborn error of metabolism v2.199 CLPB Arina Puzriakova Publications for gene: CLPB were set to 25597510; 25597511; 25650066; 25595726
Likely inborn error of metabolism v2.198 CLPB Arina Puzriakova Tag Q4_21_MOI tag was added to gene: CLPB.
Likely inborn error of metabolism v2.198 CLPB Arina Puzriakova Added comment: Comment on mode of inheritance: MOI should be updated from 'Biallelic' to 'Both mono- and biallelic' at the next GMS update.

Wortmann et al. 2021 (PMID: 34140661) published six unrelated individuals with one of four different de novo monoallelic missense variants in CLPB. The phenotype overlapped with that observed in the recessive disease including neurodevelopmental delay, seizures, 3-MGA-uria, and neutropenia. Some functional studies of heterozygous variants were performed.
Likely inborn error of metabolism v2.198 CLPB Arina Puzriakova Mode of inheritance for gene: CLPB was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v2.60 CLPB Arina Puzriakova Phenotypes for gene: CLPB were changed from 3-methylglutaconic aciduria with the following: cataract, renal cysts and nephrocalcinosis; progressive brain atrophy, intellectual disability, congenital neutropenia, cataracts, movement disorder; cataract, neutropenia, epilepsy; congenital microcephaly and severe encephalopathy to 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropenia, OMIM:616271
Childhood onset dystonia, chorea or related movement disorder v1.197 CLPB Arina Puzriakova Phenotypes for gene: CLPB were changed from 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropenia, 616271 to 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropenia, OMIM:616271
Early onset or syndromic epilepsy v2.465 CLPB Arina Puzriakova Phenotypes for gene: CLPB were changed from Seizures; Generalised epilepsy; 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropenia, 616271 to 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropenia, OMIM:616271
Fetal anomalies v1.810 CLPB Arina Puzriakova Phenotypes for gene: CLPB were changed from 3-METHYLGLUTACONIC ACIDURIA, TYPE VII, WITH CATARACTS, NEUROLOGIC INVOLVEMENT AND NEUTROPENIA to 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropenia, OMIM:616271
Possible mitochondrial disorder - nuclear genes v1.57 CLPB Arina Puzriakova Phenotypes for gene: CLPB were changed from 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropenia, 616271 to 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropenia, OMIM:616271
Primary immunodeficiency or monogenic inflammatory bowel disease v2.494 CLPB Arina Puzriakova Phenotypes for gene: CLPB were changed from 3-methylglutaconic aciduria, type VII; 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropenia, 616271; 3-methylglutaconic aciduria, type 7; Recurrent or severe infection; Neurocognitive developmental aberrations, microcephaly, hypoglycemia, hypotonia, ataxia, seizures, cataracts, IUGR; Congenital defects of phagocyte number or function to 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropenia, OMIM:616271
Undiagnosed metabolic disorders v1.495 CLPB Arina Puzriakova Phenotypes for gene: CLPB were changed from 3-methylglutaconic aciduria with the following: cataract, renal cysts and nephrocalcinosis; progressive brain atrophy, intellectual disability, congenital neutropenia, cataracts, movement disorder; cataract, neutropenia, epilepsy; congenital microcephaly and severe encephalopathy to 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropenia, OMIM:616271
Likely inborn error of metabolism v2.197 CLPB Arina Puzriakova Phenotypes for gene: CLPB were changed from 3-methylglutaconic aciduria with the following: cataract, renal cysts and nephrocalcinosis; cataract, neutropenia, epilepsy; congenital microcephaly and severe encephalopathy; progressive brain atrophy, intellectual disability, congenital neutropenia, cataracts, movement disorder to 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropenia, OMIM:616271
Cytopenia - NOT Fanconi anaemia v1.44 CLPB Arina Puzriakova Phenotypes for gene: CLPB were changed from 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropenia, 616271 to 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropenia, OMIM:616271
Primary immunodeficiency or monogenic inflammatory bowel disease v2.493 IKZF3 Arina Puzriakova changed review comment from: Comment on mode of inheritance: Upgraded from Red to Amber but there is now enough evidence to promote this gene to Green at the next GMS panel update. Two unrelated families displaying comparable immunologic disorders including T and B cell abnormalities with recurrent infections (PMID: 34155405; 34694366). Strong functional support including animal model and in vitro studies.; to: Comment on list classification: Upgraded from Red to Amber but there is now enough evidence to promote this gene to Green at the next GMS panel update. Two unrelated families displaying comparable immunologic disorders including T and B cell abnormalities with recurrent infections (PMID: 34155405; 34694366). Strong functional support including animal model and in vitro studies.
Primary immunodeficiency or monogenic inflammatory bowel disease v2.493 IKZF3 Arina Puzriakova Classified gene: IKZF3 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v2.493 IKZF3 Arina Puzriakova Gene: ikzf3 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v2.492 IKZF3 Arina Puzriakova edited their review of gene: IKZF3: Changed rating: GREEN
Primary immunodeficiency or monogenic inflammatory bowel disease v2.492 IKZF3 Arina Puzriakova Added comment: Comment on mode of inheritance: Upgraded from Red to Amber but there is now enough evidence to promote this gene to Green at the next GMS panel update. Two unrelated families displaying comparable immunologic disorders including T and B cell abnormalities with recurrent infections (PMID: 34155405; 34694366). Strong functional support including animal model and in vitro studies.
Primary immunodeficiency or monogenic inflammatory bowel disease v2.492 IKZF3 Arina Puzriakova Mode of inheritance for gene: IKZF3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v2.491 IKZF3 Arina Puzriakova Added comment: Comment on mode of pathogenicity: Variants discovered to date located in DNA binding domain of IKZF3/AIOLOS, with dominant-negative effect on WT.
Primary immunodeficiency or monogenic inflammatory bowel disease v2.491 IKZF3 Arina Puzriakova Mode of pathogenicity for gene: IKZF3 was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Primary immunodeficiency or monogenic inflammatory bowel disease v2.490 IKZF3 Arina Puzriakova Publications for gene: IKZF3 were set to 34155405
Primary immunodeficiency or monogenic inflammatory bowel disease v2.489 IKZF3 Arina Puzriakova Tag Q4_21_rating tag was added to gene: IKZF3.
Primary immunodeficiency or monogenic inflammatory bowel disease v2.489 IKZF3 Arina Puzriakova Phenotypes for gene: IKZF3 were changed from B cell deficiency; EBV inefctions suspectibility; hypogammaglobulinemia to Immunodeficiency 84, OMIM:619437
Primary immunodeficiency or monogenic inflammatory bowel disease v2.488 DEF6 Arina Puzriakova Tag Q4_21_rating tag was added to gene: DEF6.
Primary immunodeficiency or monogenic inflammatory bowel disease v2.488 DEF6 Arina Puzriakova Classified gene: DEF6 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v2.488 DEF6 Arina Puzriakova Added comment: Comment on list classification: There are now at least 3 unrelated cases of immunodeficiency associated with different biallelic variants in this gene (PMID:31308374; 32562707). DEF6 is also associated with a relevant phenotype in OMIM (MIM# 619573) and should be promoted to Green at the next GMS panel update (tagged).
Primary immunodeficiency or monogenic inflammatory bowel disease v2.488 DEF6 Arina Puzriakova Gene: def6 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v2.487 DEF6 Arina Puzriakova Publications for gene: DEF6 were set to 32086639; 31308374; 32048120
Primary immunodeficiency or monogenic inflammatory bowel disease v2.486 DEF6 Arina Puzriakova Phenotypes for gene: DEF6 were changed from DEF6 deficiency; Enteropathy, hepatosplenomegaly, cardiomyopathy, recurrent infections; Diseases of Immune Dysregulation to Immunodeficiency 87 and autoimmunity, OMIM:619573; Enteropathy, hepatosplenomegaly, cardiomyopathy, recurrent infections
Cytopenia - NOT Fanconi anaemia v1.43 RPA1 Dmitrijs Rots gene: RPA1 was added
gene: RPA1 was added to Cytopenia - NOT Fanconi anaemia. Sources: Literature
Mode of inheritance for gene: RPA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RPA1 were set to bone marrow failure; T- and B-cell lymphopenia; pulmonary fibrosis; skin manifestations.
Penetrance for gene: RPA1 were set to unknown
Mode of pathogenicity for gene: RPA1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: RPA1 was set to GREEN
Added comment: 4 cases with gain of function mutations with "including bone marrow failure, myelodysplastic syndrome, T- and B-cell lymphopenia, pulmonary fibrosis, or skin manifestations." described in
https://doi.org/10.1182/blood.2021011980
Sources: Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v2.485 UBA1 Dmitrijs Rots reviewed gene: UBA1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34048852; Phenotypes: VEXAS autoinflammatory condition; Mode of inheritance: Other
Fetal anomalies v1.809 AR Arina Puzriakova Phenotypes for gene: AR were changed from ANDROGEN INSENSITIVITY SYNDROME; SPINAL AND BULBAR MUSCULAR ATROPHY to ANDROGEN INSENSITIVITY SYNDROME
Differences in sex development v2.52 AR Arina Puzriakova Phenotypes for gene: AR were changed from Gender Assignment Gene Panel UKGTN; Androgen insensitivity, OMIM:300068; Androgen insensitivity,partial,with/without breast cancer, OMIM:312300; Hypospadias 1,X-linked, OMIM:300633 to Androgen insensitivity, OMIM:300068; Androgen insensitivity, partial, with or without breast cancer, OMIM:312300; Hypospadias 1, X-linked, OMIM:300633
Ectodermal dysplasia v1.27 AR Arina Puzriakova Phenotypes for gene: AR were changed from Androgen insensitivity, 300068; Androgen insensitivity, partial, with or without breast cancer, 312300; Hypospadias 1, X-linked, 300633; Spinal and bulbar muscular atrophy of Kennedy, 313200 to Androgen insensitivity, OMIM:300068; Androgen insensitivity, partial, with or without breast cancer, OMIM:312300; Hypospadias 1, X-linked, OMIM:300633; Spinal and bulbar muscular atrophy of Kennedy, OMIM:313200
Hereditary ataxia with onset in adulthood v2.126 RFC1 Michael Bonello reviewed gene: RFC1: Rating: GREEN; Mode of pathogenicity: Other; Publications: 32582864, 31824583, 33969391; Phenotypes: CANVAS Syndrome, Cerebellar ataxia, Idiopathic Sensory Neuropathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Inherited ovarian cancer (without breast cancer) v2.22 AR Arina Puzriakova Phenotypes for gene: AR were changed from Androgen insensitivity, 300068; Spinal and bulbar muscular atrophy of Kennedy, 313200; Androgen insensitivity, partial, with or without breast cancer, 312300; {Prostate cancer, susceptibility to}, 176807; Hypospadias 1, X-linked, 300633 to Androgen insensitivity, OMIM:300068; Androgen insensitivity, partial, with or without breast cancer, OMIM:312300
Adult onset neurodegenerative disorder v2.250 AR Arina Puzriakova Phenotypes for gene: AR were changed from Spinal and bulbar muscular atrophy of Kennedy, 313200 to Spinal and bulbar muscular atrophy of Kennedy, OMIM:313200
Familial breast cancer v1.15 AR Arina Puzriakova Phenotypes for gene: AR were changed from Androgen insensitivity, 300068; Spinal and bulbar muscular atrophy of Kennedy, 313200; Androgen insensitivity, partial, with or without breast cancer, 312300; {Prostate cancer, susceptibility to}, 176807; Hypospadias 1, X-linked, 300633 to Androgen insensitivity, partial, with or without breast cancer, OMIM:312300
Intellectual disability v3.1454 AR Arina Puzriakova Phenotypes for gene: AR were changed from Spinal and bulbar muscular atrophy of Kennedy, OMIM:313200 to Androgen insensitivity, OMIM:300068; Androgen insensitivity, partial, with or without breast cancer, OMIM:312300; Hypospadias 1, X-linked, OMIM:300633; Spinal and bulbar muscular atrophy of Kennedy, OMIM:313200
Paediatric motor neuronopathies v1.72 AR Arina Puzriakova Tag Q2_21_MOI tag was added to gene: AR.
Paediatric motor neuronopathies v1.72 AR Arina Puzriakova Added comment: Comment on mode of inheritance: MOI should be changed to 'Other' to maintain consistency with other panels for this phenotype due to lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Paediatric motor neuronopathies v1.72 AR Arina Puzriakova Mode of inheritance for gene: AR was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Adult onset neurodegenerative disorder v2.249 AR Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Adult onset neurodegenerative disorder v2.249 AR Arina Puzriakova Mode of inheritance for gene: AR was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to Other
Amyotrophic lateral sclerosis/motor neuron disease v1.49 AR Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Amyotrophic lateral sclerosis/motor neuron disease v1.49 AR Arina Puzriakova Mode of inheritance for gene: AR was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to Other
Hereditary neuropathy or pain disorder v1.67 AR_CAG Arina Puzriakova Phenotypes for STR: AR_CAG were changed from Spinal and bulbar muscular atrophy or Kennedy diseases 313200 to Spinal and bulbar muscular atrophy of Kennedy, OMIM:313200
Hereditary neuropathy v1.430 AR_CAG Arina Puzriakova Phenotypes for STR: AR_CAG were changed from Spinal and bulbar muscular atrophy or Kennedy diseases 313200 to Spinal and bulbar muscular atrophy of Kennedy, OMIM:313200
Amyotrophic lateral sclerosis/motor neuron disease v1.48 AR_CAG Arina Puzriakova Phenotypes for STR: AR_CAG were changed from Spinal and bulbar muscular atrophy or Kennedy diseases, OMIM:313200 to Spinal and bulbar muscular atrophy of Kennedy, OMIM:313200
Adult onset neurodegenerative disorder v2.248 AR_CAG Arina Puzriakova Phenotypes for STR: AR_CAG were changed from Spinal and bulbar muscular atrophy or Kennedy diseases 313200 to Spinal and bulbar muscular atrophy of Kennedy, OMIM:313200
Congenital myopathy v2.68 AR_CAG Arina Puzriakova Phenotypes for STR: AR_CAG were changed from Spinal and bulbar muscular atrophy or Kennedy diseases 313200 to Spinal and bulbar muscular atrophy of Kennedy, OMIM:313200
Distal myopathies v1.38 AR_CAG Arina Puzriakova Phenotypes for STR: AR_CAG were changed from Spinal and bulbar muscular atrophy or Kennedy diseases 313200 to Spinal and bulbar muscular atrophy of Kennedy, OMIM:313200
Paediatric motor neuronopathies v1.71 AR_CAG Arina Puzriakova changed review comment from: Comment on list classification: There is sufficient evidence to promote this STR to Green at the next GMS panel update.

The AR gene was already Green on this panel for Kennedy disease, MIM# 313200 (https://panelapp.genomicsengland.co.uk/panels/79/gene/AR/); however, this was downgraded as the disease mechanism is an expansion of 36 or more CAG trinucleotide repeats in the AR gene and there is a lack of phenotypic relevance for SNVs. STR testing is appropriate route for detecting cases.; to: Comment on list classification: There is sufficient evidence to promote this STR to Green at the next GMS panel update.

The AR gene was Green on this panel for Kennedy disease, MIM# 313200 (https://panelapp.genomicsengland.co.uk/panels/79/gene/AR/); however, this has been flagged to be downgraded as the disease mechanism is an expansion of 36 or more CAG trinucleotide repeats in the AR gene and there is a lack of phenotypic relevance for SNVs. STR testing is appropriate route for detecting cases.
Adult onset neurodegenerative disorder v2.247 FXN_GAA Arina Puzriakova Phenotypes for STR: FXN_GAA were changed from Friedreich ataxia 229300 to Friedreich ataxia, OMIM:229300; Friedreich ataxia with retained reflexes, OMIM:229300
Adult onset neurodegenerative disorder v2.246 FXN_GAA Arina Puzriakova Tag watchlist tag was added to STR: FXN_GAA.
Hereditary neuropathy v1.429 FXN_GAA Arina Puzriakova Phenotypes for STR: FXN_GAA were changed from Friedreich ataxia 229300 to Friedreich ataxia, OMIM:229300; Friedreich ataxia with retained reflexes, OMIM:229300
Mitochondrial disorders v2.59 FXN_GAA Arina Puzriakova Phenotypes for STR: FXN_GAA were changed from Friedreich ataxia 229300 to Friedreich ataxia, OMIM:229300; Friedreich ataxia with retained reflexes, OMIM:229300
Hereditary ataxia with onset in adulthood v2.126 FXN_GAA Arina Puzriakova Phenotypes for STR: FXN_GAA were changed from Friedreich ataxia 229300 to Friedreich ataxia, OMIM:229300; Friedreich ataxia with retained reflexes, OMIM:229300
Adult onset hereditary spastic paraplegia v1.83 FXN_GAA Arina Puzriakova Phenotypes for STR: FXN_GAA were changed from Friedreich ataxia 229300 to Friedreich ataxia, OMIM:229300; Friedreich ataxia with retained reflexes, OMIM:229300
Childhood onset hereditary spastic paraplegia v2.97 FXN_GAA Arina Puzriakova Phenotypes for STR: FXN_GAA were changed from Friedreich ataxia 229300 to Friedreich ataxia, OMIM:229300; Friedreich ataxia with retained reflexes, OMIM:229300
Hereditary spastic paraplegia v1.271 FXN_GAA Arina Puzriakova Phenotypes for STR: FXN_GAA were changed from Friedreich ataxia 229300 to Friedreich ataxia, OMIM:229300; Friedreich ataxia with retained reflexes, OMIM:229300
Childhood onset dystonia, chorea or related movement disorder v1.196 FXN Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: FXN.
Mitochondrial disorders v2.58 FXN Arina Puzriakova Phenotypes for gene: FXN were changed from Friedreich ataxia, 229300; Friedreich ataxia with retained reflexes, 229300 to Friedreich ataxia, OMIM:229300; Friedreich ataxia with retained reflexes, OMIM:229300
Mitochondrial disorders v2.57 FXN Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: FXN.
Intellectual disability v3.1453 FXN Arina Puzriakova Phenotypes for gene: FXN were changed from Friedreich ataxia 229300; Friedreich ataxia with retained reflexes 229300 to Friedreich ataxia, OMIM:229300; Friedreich ataxia with retained reflexes, OMIM:229300
Possible mitochondrial disorder - nuclear genes v1.56 FXN Arina Puzriakova Phenotypes for gene: FXN were changed from Friedreich ataxia, 229300 to Friedreich ataxia, OMIM:229300; Friedreich ataxia with retained reflexes, OMIM:229300
Possible mitochondrial disorder - nuclear genes v1.55 FXN Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: FXN.
Likely inborn error of metabolism v2.196 FXN Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: FXN.
Undiagnosed metabolic disorders v1.494 FXN Arina Puzriakova Phenotypes for gene: FXN were changed from Friedreich ataxia, 229300; Friedreich ataxia with retained reflexes, 229300; Defective Fe-S/lipoic acid biosynthesis (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) to Friedreich ataxia, OMIM:229300; Friedreich ataxia with retained reflexes, OMIM:229300
Undiagnosed metabolic disorders v1.493 FXN Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: FXN.
Adult onset neurodegenerative disorder v2.246 FXN Arina Puzriakova Phenotypes for gene: FXN were changed from Friedreichataxia,229300Friedreichataxiawithretainedreflexes,229300 to Friedreich ataxia, OMIM:229300; Friedreich ataxia with retained reflexes, OMIM:229300
Adult onset hereditary spastic paraplegia v1.82 FXN Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: FXN.
Childhood onset hereditary spastic paraplegia v2.96 FXN Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: FXN.
Optic neuropathy v2.51 FXN Arina Puzriakova Phenotypes for gene: FXN were changed from Friedreich ataxia (FRDA), 229300 to Friedreich ataxia, OMIM:229300; Friedreich ataxia with retained reflexes, OMIM:229300
Optic neuropathy v2.50 FXN Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: FXN.
Hypertrophic cardiomyopathy v2.32 FXN Arina Puzriakova Phenotypes for gene: FXN were changed from syndromic HCM to Friedreich ataxia, OMIM:229300; Friedreich ataxia with retained reflexes, OMIM:229300
Ataxia and cerebellar anomalies - narrow panel v2.275 FXN Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: FXN.
Hereditary neuropathy or pain disorder v1.66 FXN Arina Puzriakova Phenotypes for gene: FXN were changed from Hereditary Neuropathies; Friedreich ataxia, 229300 to Friedreich ataxia, OMIM:229300; Friedreich ataxia with retained reflexes, OMIM:229300
Hereditary neuropathy or pain disorder v1.65 FXN Arina Puzriakova Added comment: Comment on mode of inheritance: Updated MOI to 'Biallelic' as monoallelic variants have not been associated with disease. Patients either harbour a homozygous expansion or are compound heterozygous for an expansion and a point mutation.
Hereditary neuropathy or pain disorder v1.65 FXN Arina Puzriakova Mode of inheritance for gene: FXN was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v1.64 FXN Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: FXN.
Hereditary neuropathy v1.428 FXN Arina Puzriakova Added comment: Comment on mode of inheritance: Updated MOI to 'Biallelic' as monoallelic variants have not been associated with disease. Patients either harbour a homozygous expansion or are compound heterozygous for an expansion and a point mutation.
Hereditary neuropathy v1.428 FXN Arina Puzriakova Mode of inheritance for gene: FXN was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.427 FXN Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: FXN.
Intellectual disability v3.1452 GLS_GCA Arina Puzriakova Phenotypes for STR: GLS_GCA were changed from Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412; Global developmental delay, progressive ataxia, and elevated glutamine, MONDO:0032733 to Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412
Likely inborn error of metabolism v2.196 GLS_GCA Arina Puzriakova Phenotypes for STR: GLS_GCA were changed from Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412; Global developmental delay, progressive ataxia, and elevated glutamine, MONDO:0032733 to Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412
Ataxia and cerebellar anomalies - narrow panel v2.275 GLS_GCA Arina Puzriakova Phenotypes for STR: GLS_GCA were changed from Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412; Global developmental delay, progressive ataxia, and elevated glutamine, MONDO:0032733 to Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412
Intellectual disability v3.1451 GLS Arina Puzriakova commented on gene: GLS: Added 'watchlist_MOI' tag to highlight monoallelic phenotype (MIM# 618339) which is also relevant to this panel, but as there is only a single case reported to date this is not yet sufficient to update the MOI.
Intellectual disability v3.1451 GLS Arina Puzriakova Phenotypes for gene: GLS were changed from Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412; Global developmental delay, progressive ataxia, and elevated glutamine, MONDO:0032733; ?Infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development, OMIM:618339; Infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development, MONDO:0032685 to Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412; Developmental and epileptic encephalopathy 71, OMIM:618328; ?Infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development, OMIM:618339
Intellectual disability v3.1450 GLS Arina Puzriakova Tag watchlist_moi tag was added to gene: GLS.
Ataxia and cerebellar anomalies - narrow panel v2.274 GLS Arina Puzriakova Phenotypes for gene: GLS were changed from Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412; Global developmental delay, progressive ataxia, and elevated glutamine, MONDO:0032733 to Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412
Likely inborn error of metabolism v2.195 GLS Arina Puzriakova edited their review of gene: GLS: Changed rating: GREEN
Early onset or syndromic epilepsy v2.464 GLS Arina Puzriakova Phenotypes for gene: GLS were changed from Developmental and epileptic encephalopathy 71, OMIM:618328; Developmental and epileptic encephalopathy, 71, MONDO:0032678 to Developmental and epileptic encephalopathy 71, OMIM:618328
Likely inborn error of metabolism v2.195 GLS Arina Puzriakova commented on gene: GLS: Added 'watchlist_MOI' tag to highlight monoallelic phenotype (MIM# 618339) which is also relevant to this panel, but as there is only a single case reported to date this is not yet sufficient to update the MOI.
Undiagnosed metabolic disorders v1.493 GLS Arina Puzriakova commented on gene: GLS: Added 'watchlist_MOI' tag to highlight monoallelic phenotype (MIM# 618339) which is also relevant to this panel, but as there is only a single case reported to date this is not yet sufficient to update the MOI.
Likely inborn error of metabolism v2.195 GLS Arina Puzriakova Phenotypes for gene: GLS were changed from Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412; Global developmental delay, progressive ataxia, and elevated glutamine, MONDO:0032733; Developmental and epileptic encephalopathy 71, OMIM:618328; Developmental and epileptic encephalopathy, 71, MONDO:0032678; ?Infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development, OMIM:618339; Infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development, MONDO:0032685 to Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412; Developmental and epileptic encephalopathy 71, OMIM:618328; ?Infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development, OMIM:618339
Likely inborn error of metabolism v2.194 GLS Arina Puzriakova Tag watchlist_moi tag was added to gene: GLS.
Undiagnosed metabolic disorders v1.493 GLS Arina Puzriakova Phenotypes for gene: GLS were changed from Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412; Global developmental delay, progressive ataxia, and elevated glutamine, MONDO:0032733; Developmental and epileptic encephalopathy 71, OMIM:618328; Developmental and epileptic encephalopathy, 71, MONDO:0032678; ?Infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development, OMIM:618339; Infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development, MONDO:0032685 to Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412; Developmental and epileptic encephalopathy 71, OMIM:618328; ?Infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development, OMIM:618339
Undiagnosed metabolic disorders v1.492 GLS Arina Puzriakova Tag watchlist_moi tag was added to gene: GLS.
Bilateral congenital or childhood onset cataracts v2.89 GLS Arina Puzriakova Phenotypes for gene: GLS were changed from ?Infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development, OMIM:618339; Infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development, MONDO:0032685 to ?Infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development, OMIM:618339
Hereditary ataxia with onset in adulthood v2.125 NOP56_GGCCTG Arina Puzriakova Phenotypes for STR: NOP56_GGCCTG were changed from Spinocerebellar ataxia 36 614153 to Spinocerebellar ataxia 36, OMIM:614153
Hereditary neuropathy v1.427 NOP56_GGCCTGTT Arina Puzriakova Phenotypes for STR: NOP56_GGCCTGTT were changed from to Spinocerebellar ataxia 36, OMIM:614153
Hereditary neuropathy v1.426 NOP56_GGCCTG Arina Puzriakova Phenotypes for STR: NOP56_GGCCTG were changed from Spinocerebellar ataxia 36, 614153Late adult onset gait ataxia, tongue atrophy and fasciculation, distal motor neuropathy to Spinocerebellar ataxia 36, OMIM:614153
Amyotrophic lateral sclerosis/motor neuron disease v1.47 NOP56_GGCCTG Arina Puzriakova Phenotypes for STR: NOP56_GGCCTG were changed from Spinocerebellar ataxia 36 614153 to Spinocerebellar ataxia 36, OMIM:614153
Adult onset neurodegenerative disorder v2.245 NOP56_GGCCTG Arina Puzriakova Phenotypes for STR: NOP56_GGCCTG were changed from Spinocerebellar ataxia 36 614153 to Spinocerebellar ataxia 36, OMIM:614153
Adult onset neurodegenerative disorder v2.244 NOP56_GGCCTG Arina Puzriakova Tag watchlist tag was added to STR: NOP56_GGCCTG.
Hereditary ataxia v1.279 NOP56_GGCCTG Arina Puzriakova Phenotypes for STR: NOP56_GGCCTG were changed from Spinocerebellar ataxia 36 614153 to Spinocerebellar ataxia 36, OMIM:614153
Ataxia and cerebellar anomalies - narrow panel v2.273 NOP56_GGCCTG Arina Puzriakova Phenotypes for STR: NOP56_GGCCTG were changed from Spinocerebellar ataxia 36 614153 to Spinocerebellar ataxia 36, OMIM:614153
Ataxia and cerebellar anomalies - narrow panel v2.272 NOP56_GGCCTG Arina Puzriakova Tag watchlist tag was added to STR: NOP56_GGCCTG.
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.64 NOP56_GGCCTG Arina Puzriakova Phenotypes for STR: NOP56_GGCCTG were changed from Spinocerebellar ataxia 36 614153 to Spinocerebellar ataxia 36, OMIM:614153
Childhood onset dystonia, chorea or related movement disorder v1.196 NOP56 Arina Puzriakova Classified gene: NOP56 as Red List (low evidence)
Childhood onset dystonia, chorea or related movement disorder v1.196 NOP56 Arina Puzriakova Added comment: Comment on list classification: Demoted from Amber to Red, this review is for the STR entity and not the gene entity
Childhood onset dystonia, chorea or related movement disorder v1.196 NOP56 Arina Puzriakova Gene: nop56 has been classified as Red List (Low Evidence).
Intellectual disability v3.1450 NOP56 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Intellectual disability v3.1450 NOP56 Arina Puzriakova Mode of inheritance for gene: NOP56 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Other
Childhood onset dystonia, chorea or related movement disorder v1.195 NOP56 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Childhood onset dystonia, chorea or related movement disorder v1.195 NOP56 Arina Puzriakova Mode of inheritance for gene: NOP56 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Other
Childhood onset dystonia, chorea or related movement disorder v1.194 NOP56 Arina Puzriakova Phenotypes for gene: NOP56 were changed from Spinocerebellar ataxia 36, 614153 to Spinocerebellar ataxia 36, OMIM:614153
Intellectual disability v3.1449 NOP56 Arina Puzriakova Phenotypes for gene: NOP56 were changed from Spinocerebellar ataxia 36, 614153 to Spinocerebellar ataxia 36, OMIM:614153
Childhood onset dystonia, chorea or related movement disorder v1.193 NOP56 Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: NOP56.
Tag currently-ngs-unreportable tag was added to gene: NOP56.
Hereditary ataxia with onset in adulthood v2.124 NOP56 Arina Puzriakova Phenotypes for gene: NOP56 were changed from Spinocerebellarataxia36,614153 to Spinocerebellar ataxia 36, OMIM:614153
Intellectual disability v3.1448 NOP56 Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: NOP56.
Tag currently-ngs-unreportable tag was added to gene: NOP56.
Adult onset neurodegenerative disorder v2.244 NOP56 Arina Puzriakova Phenotypes for gene: NOP56 were changed from Spinocerebellarataxia36,614153 to Spinocerebellar ataxia 36, OMIM:614153
Ataxia and cerebellar anomalies - narrow panel v2.272 NOP56 Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: NOP56.
Tag currently-ngs-unreportable tag was added to gene: NOP56.
Hereditary ataxia v1.278 NOP56 Arina Puzriakova Phenotypes for gene: NOP56 were changed from Spinocerebellarataxia36,614153 to Spinocerebellar ataxia 36, OMIM:614153
Ataxia and cerebellar anomalies - narrow panel v2.272 NOP56 Arina Puzriakova Phenotypes for gene: NOP56 were changed from Spinocerebellarataxia36,614153 to Spinocerebellar ataxia 36, OMIM:614153
Childhood onset dystonia, chorea or related movement disorder v1.193 PPP2R2B Arina Puzriakova Phenotypes for gene: PPP2R2B were changed from Spinocerebellar ataxia 12, 604326 to Spinocerebellar ataxia 12, OMIM:604326
Childhood onset dystonia, chorea or related movement disorder v1.192 PPP2R2B Arina Puzriakova Classified gene: PPP2R2B as Red List (low evidence)
Childhood onset dystonia, chorea or related movement disorder v1.192 PPP2R2B Arina Puzriakova Added comment: Comment on list classification: Demoted from Amber to Red, this review is for the STR entity and not the gene entity
Childhood onset dystonia, chorea or related movement disorder v1.192 PPP2R2B Arina Puzriakova Gene: ppp2r2b has been classified as Red List (Low Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.191 PPP2R2B Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Childhood onset dystonia, chorea or related movement disorder v1.191 PPP2R2B Arina Puzriakova Mode of inheritance for gene: PPP2R2B was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Other
Childhood onset dystonia, chorea or related movement disorder v1.190 PPP2R2B Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: PPP2R2B.
Tag currently-ngs-unreportable tag was added to gene: PPP2R2B.
Intellectual disability v3.1448 PPP2R2B Arina Puzriakova Mode of pathogenicity for gene: PPP2R2B 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
Adult onset dystonia, chorea or related movement disorder v1.157 PPP2R2B Arina Puzriakova Mode of pathogenicity for gene: PPP2R2B 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
Adult onset dystonia, chorea or related movement disorder v1.156 PPP2R2B Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Adult onset dystonia, chorea or related movement disorder v1.156 PPP2R2B Arina Puzriakova Mode of inheritance for gene: PPP2R2B was changed from to Other
Hereditary ataxia with onset in adulthood v2.123 PPP2R2B Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Hereditary ataxia with onset in adulthood v2.123 PPP2R2B Arina Puzriakova Mode of inheritance for gene: PPP2R2B was changed from Unknown to Other
Hereditary ataxia v1.277 PPP2R2B Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Hereditary ataxia v1.277 PPP2R2B Arina Puzriakova Mode of inheritance for gene: PPP2R2B was changed from to Other
Intellectual disability v3.1447 PPP2R2B Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Intellectual disability v3.1447 PPP2R2B Arina Puzriakova Mode of inheritance for gene: PPP2R2B was changed from Other - please specify in evaluation comments to Other
Ataxia and cerebellar anomalies - narrow panel v2.271 PPP2R2B Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Ataxia and cerebellar anomalies - narrow panel v2.271 PPP2R2B Arina Puzriakova Mode of inheritance for gene: PPP2R2B was changed from Unknown to Other
Adult onset neurodegenerative disorder v2.243 PPP2R2B Arina Puzriakova Mode of pathogenicity for gene: PPP2R2B 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
Adult onset neurodegenerative disorder v2.242 PPP2R2B Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Adult onset neurodegenerative disorder v2.242 PPP2R2B Arina Puzriakova Mode of inheritance for gene: PPP2R2B was changed from Unknown to Other
Adult onset dystonia, chorea or related movement disorder v1.155 PPP2R2B Arina Puzriakova Phenotypes for gene: PPP2R2B were changed from to Spinocerebellar ataxia 12, OMIM:604326
Adult onset dystonia, chorea or related movement disorder v1.154 PPP2R2B Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: PPP2R2B.
Tag currently-ngs-unreportable tag was added to gene: PPP2R2B.
Hereditary ataxia with onset in adulthood v2.122 PPP2R2B Arina Puzriakova Phenotypes for gene: PPP2R2B were changed from Spinocerebellarataxia12,604326 to Spinocerebellar ataxia 12, OMIM:604326
Hereditary ataxia with onset in adulthood v2.121 PPP2R2B Arina Puzriakova Tag watchlist was removed from gene: PPP2R2B.
Hereditary ataxia v1.276 PPP2R2B Arina Puzriakova Phenotypes for gene: PPP2R2B were changed from Spinocerebellarataxia12,604326 to Spinocerebellar ataxia 12, OMIM:604326
Intellectual disability v3.1446 PPP2R2B Arina Puzriakova Phenotypes for gene: PPP2R2B were changed from Spinocerebellar ataxia 12, 604326 to Spinocerebellar ataxia 12, OMIM:604326
Hereditary ataxia v1.275 PPP2R2B Arina Puzriakova Tag watchlist was removed from gene: PPP2R2B.
Ataxia and cerebellar anomalies - narrow panel v2.270 PPP2R2B Arina Puzriakova Phenotypes for gene: PPP2R2B were changed from Spinocerebellarataxia12,604326 to Spinocerebellar ataxia 12, OMIM:604326
Ataxia and cerebellar anomalies - narrow panel v2.269 PPP2R2B Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: PPP2R2B.
Tag currently-ngs-unreportable tag was added to gene: PPP2R2B.
Adult onset neurodegenerative disorder v2.241 PPP2R2B Arina Puzriakova Phenotypes for gene: PPP2R2B were changed from Spinocerebellarataxia12,604326 to Spinocerebellar ataxia 12, OMIM:604326
Intellectual disability v3.1445 PPP2R2B Arina Puzriakova Tag watchlist was removed from gene: PPP2R2B.
Adult onset neurodegenerative disorder v2.240 PPP2R2B Arina Puzriakova Tag watchlist was removed from gene: PPP2R2B.
Structural eye disease v1.91 FOXE3 Eleanor Williams Tag watchlist_moi tag was added to gene: FOXE3.
Structural eye disease v1.91 FOXE3 Eleanor Williams Added comment: Comment on mode of inheritance: Leaving mode of inheritance as biallelic for now. 2 monoallelic cases with coloboma, or both coloboma and microphthalmia so flagged with MOI_watchlist tag.
Structural eye disease v1.91 FOXE3 Eleanor Williams Mode of inheritance for gene: FOXE3 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v1.90 FOXE3 Eleanor Williams Phenotypes for gene: FOXE3 were changed from Anterior segment mesenchymal dysgenesis 107250; Anterior segment dysgenesis 2, multiple subtypes 610256 to Anterior segment mesenchymal dysgenesis, OMIM:107250; Anterior segment dysgenesis 2, multiple subtypes, OMIM:610256
Structural eye disease v1.89 FOXE3 Eleanor Williams Publications for gene: FOXE3 were set to 16826526; 24859618, 19708017; 20361012; 11159941; 27218149; 21150893
Structural eye disease v1.88 FOXE3 Eleanor Williams changed review comment from: Review of mode of inheritance:

There are many reported cases of biallelic variants in FOXE3 associated with an eye phenotype, particularly cataracts, aphakia, microphthalmia and sclerocornea (PMID: 27218149 Khan et al 2016, PMID: 16826526 Valleix et al 2006, PMID: 19708017 Iseri et al 2009, PMID: 20140963 Reis et al 2010, PMID: 20664696 Ali et al 2010, PMID: 20361012 Anjum et al 2010, PMID: 24019743 Pantoja-Melendez et al 2013, PMID: 27669367 Saboo et al 2017, PMID: 29878917 Quiroz-Casian et al 2018, PMID: 32436650 Taha Najim et al 2020, PMID: 34046667 Reis et al 2021). Glaucoma is also noted in some individuals. Heterozygous carriers are largely unaffected in these cases.

Patients with monoallelic variants in FOXE3 and an eye phenotype are also reported:

PMID: 11159941 - Semina et al 2001 - screened FOXE3 in a cohort of 161 unrelated individuals affected with anterior segment ocular disorders and identified a 1 bp insertion in FOXE3 in a proband and affected mother that was not found in controls. Both affected individuals had prominent anterior Schwalbe’s line (posterior embryotoxon) and cataracts.

PMID: 19708017 - Iseri et al 2009 - identified 2 pedigrees with dominant mutations in the FOXE3 gene by screening a large cohort of 236 anophthalmia-microphthalmia subjects; one with anterior segment anomalies, including Peters’ anomaly, early onset cataract, and coloboma, and another with microphthalmia,coloboma, and cerulean type (blue dot) cataracts.

PMID: 20806047 - Bremond-Ginac et al 2010 - a dominant mutation at the stop codon of FOXE3, c.959G>C (p.X320SerextX72), was identified in a patient with congenital cataract.

PMID: 21150893 - Doucette et al 2011 - sequenced 9 candidate genes in a large Newfoundland family with 11 relatives have a variable ocular phenotype ranging from microcornea to Peters anomaly and found a c.959G>T) substitution that replaces the stop codon for a leucine residue, predicting the addition of 72 amino acids to the C-terminus of FOXE3. Analysis of lympohocytes suggests the c.959T allele is absent rather than an extended protein being expressed.

PMID: 11980846 - Ormestad et al 2002 - one individual with Peters anomaly (with eccentric corneal opacities and glaucoma but not cataract) was found to be heterozygous for a nonconservative missense mutation in FOXE3. 40% of mice heterozygous for Foxe3(dyl) have corneal and lenticular defects.

PMID: 34046667 - Reis et al 2021 - 2 families reported with dominant pathogenic extension alleles which modify the stop codon but keep the amino acids in frame, adding a 72–amino acid nonsense peptide. Cataracts were found in all cases where the lens could be evaluated. Eye size was normal in all individuals, but mild anterior segment anomalies affecting the cornea and/or iris were noted in some individuals. Sclerocornea was observed in two family members (15C and 16B).; to: Review of mode of inheritance:

There are many reported cases of biallelic variants in FOXE3 associated with an eye phenotype, particularly cataracts, aphakia, microphthalmia and sclerocornea (PMID: 27218149 Khan et al 2016, PMID: 16826526 Valleix et al 2006, PMID: 19708017 Iseri et al 2009, PMID: 20140963 Reis et al 2010, PMID: 20664696 Ali et al 2010, PMID: 20361012 Anjum et al 2010, PMID: 24019743 Pantoja-Melendez et al 2013, PMID: 27669367 Saboo et al 2017, PMID: 29878917 Quiroz-Casian et al 2018, PMID: 32436650 Taha Najim et al 2020, PMID: 34046667 Reis et al 2021). Glaucoma is also noted in some individuals. Heterozygous carriers are largely unaffected in these cases.

Patients with monoallelic variants in FOXE3 and an eye phenotype are also reported, but only 2 patients show coloboma, or both coloboma and microphthalmia (both reported in Iseri et al 2009).

PMID: 11159941 - Semina et al 2001 - screened FOXE3 in a cohort of 161 unrelated individuals affected with anterior segment ocular disorders and identified a 1 bp insertion in FOXE3 in a proband and affected mother that was not found in controls. Both affected individuals had prominent anterior Schwalbe’s line (posterior embryotoxon) and cataracts.

PMID: 19708017 - Iseri et al 2009 - identified 2 pedigrees with dominant mutations in the FOXE3 gene by screening a large cohort of 236 anophthalmia-microphthalmia subjects; one with anterior segment anomalies, including Peters’ anomaly, early onset cataract, and coloboma, and another with microphthalmia, coloboma, and cerulean type (blue dot) cataracts.

PMID: 20806047 - Bremond-Ginac et al 2010 - a dominant mutation at the stop codon of FOXE3, c.959G>C (p.X320SerextX72), was identified in a patient with congenital cataract.

PMID: 21150893 - Doucette et al 2011 - sequenced 9 candidate genes in a large Newfoundland family with 11 relatives have a variable ocular phenotype ranging from microcornea to Peters anomaly and found a c.959G>T) substitution that replaces the stop codon for a leucine residue, predicting the addition of 72 amino acids to the C-terminus of FOXE3. Analysis of lympohocytes suggests the c.959T allele is absent rather than an extended protein being expressed.

PMID: 11980846 - Ormestad et al 2002 - one individual with Peters anomaly (with eccentric corneal opacities and glaucoma but not cataract) was found to be heterozygous for a nonconservative missense mutation in FOXE3. 40% of mice heterozygous for Foxe3(dyl) have corneal and lenticular defects.

PMID: 34046667 - Reis et al 2021 - 2 families reported with dominant pathogenic extension alleles which modify the stop codon but keep the amino acids in frame, adding a 72–amino acid nonsense peptide. Cataracts were found in all cases where the lens could be evaluated. Eye size was normal in all individuals, but mild anterior segment anomalies affecting the cornea and/or iris were noted in some individuals. Sclerocornea was observed in two family members (15C and 16B).
Adult onset dystonia, chorea or related movement disorder v1.154 PPP2R2B_CAG Arina Puzriakova Phenotypes for STR: PPP2R2B_CAG were changed from Spinocerebellar ataxia 12 604326 to Spinocerebellar ataxia 12, OMIM:604326
Adult onset dystonia, chorea or related movement disorder v1.153 PPP2R2B_CAG Arina Puzriakova Tag watchlist tag was added to STR: PPP2R2B_CAG.
Intellectual disability v3.1445 PPP2R2B_CAG Arina Puzriakova Phenotypes for STR: PPP2R2B_CAG were changed from Spinocerebellar ataxia 12 604326 to Spinocerebellar ataxia 12, OMIM:604326
Hereditary ataxia with onset in adulthood v2.121 PPP2R2B_CAG Arina Puzriakova Phenotypes for STR: PPP2R2B_CAG were changed from Spinocerebellar ataxia 12 604326 to Spinocerebellar ataxia 12, OMIM:604326
Hereditary neuropathy v1.425 PPP2R2B_CAG Arina Puzriakova Phenotypes for STR: PPP2R2B_CAG were changed from Spinocerebellar ataxia 12 604326; Adult onset cerebellar ataxia, tremor of head and arms, subclinical sensory-motor axonal neuropathy; neuropathy minor feature to Spinocerebellar ataxia 12, OMIM:604326
Adult onset neurodegenerative disorder v2.240 PPP2R2B_CAG Arina Puzriakova Phenotypes for STR: PPP2R2B_CAG were changed from Spinocerebellar ataxia 12 604326 to Spinocerebellar ataxia 12, OMIM:604326
Adult onset neurodegenerative disorder v2.239 PPP2R2B_CAG Arina Puzriakova Tag watchlist tag was added to STR: PPP2R2B_CAG.
Adult onset hereditary spastic paraplegia v1.82 PPP2R2B_CAG Arina Puzriakova Phenotypes for STR: PPP2R2B_CAG were changed from Spinocerebellar ataxia 12 604326 to Spinocerebellar ataxia 12, OMIM:604326
Childhood onset hereditary spastic paraplegia v2.96 PPP2R2B_CAG Arina Puzriakova Phenotypes for STR: PPP2R2B_CAG were changed from Spinocerebellar ataxia 12 604326 to Spinocerebellar ataxia 12, OMIM:604326
Hereditary spastic paraplegia v1.270 PPP2R2B_CAG Arina Puzriakova Phenotypes for STR: PPP2R2B_CAG were changed from Spinocerebellar ataxia 12 604326 to Spinocerebellar ataxia 12, OMIM:604326
Hereditary ataxia v1.275 PPP2R2B_CAG Arina Puzriakova Phenotypes for STR: PPP2R2B_CAG were changed from Spinocerebellar ataxia 12 604326 to Spinocerebellar ataxia 12, OMIM:604326
Ataxia and cerebellar anomalies - narrow panel v2.269 PPP2R2B_CAG Arina Puzriakova Phenotypes for STR: PPP2R2B_CAG were changed from Spinocerebellar ataxia 12 604326 to Spinocerebellar ataxia 12, OMIM:604326
Ataxia and cerebellar anomalies - narrow panel v2.268 PPP2R2B_CAG Arina Puzriakova Tag watchlist tag was added to STR: PPP2R2B_CAG.
Parkinson Disease and Complex Parkinsonism v1.92 PPP2R2B_CAG Arina Puzriakova Phenotypes for STR: PPP2R2B_CAG were changed from Spinocerebellar ataxia 12 604326 to Spinocerebellar ataxia 12, OMIM:604326
Childhood onset dystonia, chorea or related movement disorder v1.190 TBP_CAG Arina Puzriakova Phenotypes for STR: TBP_CAG were changed from Spinocerebellar ataxia 17, 607136 to Spinocerebellar ataxia 17, OMIM:607136
Hereditary ataxia with onset in adulthood v2.120 TBP_CAG Arina Puzriakova Phenotypes for STR: TBP_CAG were changed from Spinocerebellar ataxia 17 607136 to Spinocerebellar ataxia 17, OMIM:607136
Adult onset hereditary spastic paraplegia v1.81 TBP_CAG Arina Puzriakova Phenotypes for STR: TBP_CAG were changed from Spinocerebellar ataxia 17 607136 to Spinocerebellar ataxia 17, OMIM:607136
Childhood onset hereditary spastic paraplegia v2.95 TBP_CAG Arina Puzriakova Phenotypes for STR: TBP_CAG were changed from Spinocerebellar ataxia 17 607136 to Spinocerebellar ataxia 17, OMIM:607136
Hereditary spastic paraplegia v1.269 TBP_CAG Arina Puzriakova Phenotypes for STR: TBP_CAG were changed from Spinocerebellar ataxia 17 607136 to Spinocerebellar ataxia 17, OMIM:607136
Hereditary ataxia v1.274 TBP_CAG Arina Puzriakova Phenotypes for STR: TBP_CAG were changed from Spinocerebellar ataxia 17 607136 to Spinocerebellar ataxia 17, OMIM:607136
Ataxia and cerebellar anomalies - narrow panel v2.268 TBP_CAG Arina Puzriakova Phenotypes for STR: TBP_CAG were changed from Spinocerebellar ataxia 17 607136 to Spinocerebellar ataxia 17, OMIM:607136
Ataxia and cerebellar anomalies - narrow panel v2.267 TBP_CAG Arina Puzriakova Tag watchlist tag was added to STR: TBP_CAG.
Brain channelopathy v1.70 TBP_CAG Arina Puzriakova Phenotypes for STR: TBP_CAG were changed from Spinocerebellar ataxia 17 607136 to Spinocerebellar ataxia 17, OMIM:607136
Adult onset dystonia, chorea or related movement disorder v1.153 TBP_CAG Arina Puzriakova Phenotypes for STR: TBP_CAG were changed from Spinocerebellar ataxia 17 607136 to Spinocerebellar ataxia 17, OMIM:607136; {Parkinson disease, susceptibility to}, OMIM:168600
Adult onset neurodegenerative disorder v2.239 TBP_CAG Arina Puzriakova Phenotypes for STR: TBP_CAG were changed from Spinocerebellar ataxia 17 607136 to Spinocerebellar ataxia 17, OMIM:607136; {Parkinson disease, susceptibility to}, OMIM:168600
Adult onset neurodegenerative disorder v2.238 TBP_CAG Arina Puzriakova Tag watchlist tag was added to STR: TBP_CAG.
Paroxysmal central nervous system disorders v1.34 TBP_CAG Arina Puzriakova Phenotypes for STR: TBP_CAG were changed from Spinocerebellar ataxia 17 607136 to Spinocerebellar ataxia 17, OMIM:607136; {Parkinson disease, susceptibility to}, OMIM:168600
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.63 TBP_CAG Arina Puzriakova Phenotypes for STR: TBP_CAG were changed from Spinocerebellar ataxia 17 607136 to Spinocerebellar ataxia 17, OMIM:607136; {Parkinson disease, susceptibility to}, OMIM:168600
Parkinson Disease and Complex Parkinsonism v1.91 TBP_CAG Arina Puzriakova Phenotypes for STR: TBP_CAG were changed from Spinocerebellar ataxia 17 607136 to Spinocerebellar ataxia 17, OMIM:607136; {Parkinson disease, susceptibility to}, OMIM:168600
Intellectual disability v3.1444 TBP Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Intellectual disability v3.1444 TBP Arina Puzriakova Mode of inheritance for gene: TBP was changed from Other - please specify in evaluation comments to Other
Intellectual disability v3.1443 TBP Arina Puzriakova Mode of pathogenicity for gene: TBP 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
Adult onset neurodegenerative disorder v2.238 TBP Arina Puzriakova Mode of pathogenicity for gene: TBP 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
Paroxysmal central nervous system disorders v1.33 TBP Arina Puzriakova Mode of pathogenicity for gene: TBP 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
Adult onset dystonia, chorea or related movement disorder v1.152 TBP Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Adult onset dystonia, chorea or related movement disorder v1.152 TBP Arina Puzriakova Mode of inheritance for gene: TBP was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Other
Hereditary ataxia with onset in adulthood v2.119 TBP Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Hereditary ataxia with onset in adulthood v2.119 TBP Arina Puzriakova Mode of inheritance for gene: TBP was changed from Unknown to Other
Adult onset neurodegenerative disorder v2.237 TBP Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Adult onset neurodegenerative disorder v2.237 TBP Arina Puzriakova Mode of inheritance for gene: TBP was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Other
Paroxysmal central nervous system disorders v1.32 TBP Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Paroxysmal central nervous system disorders v1.32 TBP Arina Puzriakova Mode of inheritance for gene: TBP was changed from to Other
Hereditary ataxia v1.273 TBP Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Hereditary ataxia v1.273 TBP Arina Puzriakova Mode of inheritance for gene: TBP was changed from to Other
Ataxia and cerebellar anomalies - narrow panel v2.267 TBP Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Ataxia and cerebellar anomalies - narrow panel v2.267 TBP Arina Puzriakova Mode of inheritance for gene: TBP was changed from Unknown to Other
Parkinson Disease and Complex Parkinsonism v1.90 TBP Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Parkinson Disease and Complex Parkinsonism v1.90 TBP Arina Puzriakova Mode of inheritance for gene: TBP was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Other
Adult onset dystonia, chorea or related movement disorder v1.151 TBP Arina Puzriakova Phenotypes for gene: TBP were changed from {Parkinson disease, susceptibility to}, 168600; Mohr-Tranebjaerg syndrome, 304700; Spinocerebellar ataxia 17, 607136 to Spinocerebellar ataxia 17, OMIM:607136; {Parkinson disease, susceptibility to}, OMIM:168600
Adult onset dystonia, chorea or related movement disorder v1.150 TBP Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: TBP.
Tag currently-ngs-unreportable tag was added to gene: TBP.
Intellectual disability v3.1442 TBP Arina Puzriakova Phenotypes for gene: TBP were changed from Spinocerebellar ataxia 17, 607136; {Parkinson disease, susceptibility to}, 168600 to Spinocerebellar ataxia 17, OMIM:607136
Hereditary ataxia with onset in adulthood v2.118 TBP Arina Puzriakova Phenotypes for gene: TBP were changed from Spinocerebellarataxia17,607136{Parkinsondisease,susceptibilityto},168600 to Spinocerebellar ataxia 17, OMIM:607136
Intellectual disability v3.1441 TBP Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: TBP.
Tag currently-ngs-unreportable tag was added to gene: TBP.
Adult onset neurodegenerative disorder v2.236 TBP Arina Puzriakova Phenotypes for gene: TBP were changed from Spinocerebellar ataxia 17, 607136; Spinocerebellarataxia17,607136{Parkinsondisease,susceptibilityto},168600; {Parkinson disease, susceptibility to}, 168600 to Spinocerebellar ataxia 17, OMIM:607136; {Parkinson disease, susceptibility to}, OMIM:168600
Paroxysmal central nervous system disorders v1.31 TBP Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: TBP.
Tag currently-ngs-unreportable tag was added to gene: TBP.
Paroxysmal central nervous system disorders v1.31 TBP Arina Puzriakova Phenotypes for gene: TBP were changed from to Spinocerebellar ataxia 17, OMIM:607136; {Parkinson disease, susceptibility to}, OMIM:168600
Hereditary ataxia v1.272 TBP Arina Puzriakova Phenotypes for gene: TBP were changed from Spinocerebellarataxia17,607136{Parkinsondisease,susceptibilityto},168600 to Spinocerebellar ataxia 17, OMIM:607136
Ataxia and cerebellar anomalies - narrow panel v2.266 TBP Arina Puzriakova Phenotypes for gene: TBP were changed from Spinocerebellarataxia17,607136{Parkinsondisease,susceptibilityto},168600 to Spinocerebellar ataxia 17, OMIM:607136
Ataxia and cerebellar anomalies - narrow panel v2.265 TBP Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: TBP.
Tag currently-ngs-unreportable tag was added to gene: TBP.
Parkinson Disease and Complex Parkinsonism v1.89 TBP Arina Puzriakova Phenotypes for gene: TBP were changed from Spinocerebellar ataxia 17, 607136; {Parkinson disease, susceptibility to}, 168600 to Spinocerebellar ataxia 17, OMIM:607136; {Parkinson disease, susceptibility to}, OMIM:168600
Parkinson Disease and Complex Parkinsonism v1.88 TBP Arina Puzriakova Tag currently-ngs-unreportable tag was added to gene: TBP.
Adult onset leukodystrophy v1.35 RNASET2 Ivone Leong Tag Q4_21_expert_review tag was added to gene: RNASET2.
Adult onset leukodystrophy v1.35 POLR1C Ivone Leong Tag Q4_21_expert_review tag was added to gene: POLR1C.
Adult onset leukodystrophy v1.35 MARS Ivone Leong Tag Q4_21_expert_review tag was added to gene: MARS.
Tag Q4_21_phenotype tag was added to gene: MARS.
Rare genetic inflammatory skin disorders v1.42 RNU12 Eleanor Williams Tag Q4_21_phenotype tag was added to gene: RNU12.
Rare genetic inflammatory skin disorders v1.42 RNU12 Eleanor Williams Classified gene: RNU12 as Amber List (moderate evidence)
Rare genetic inflammatory skin disorders v1.42 RNU12 Eleanor Williams Added comment: Comment on list classification: Promoted from red to amber. It could be promoted to green after GMS review if the working group decide that the phenotype is appropriate for this panel. However, variants in this gene would not currently be reported as it is not a protein coding gene. An Ensembl ID also needs to be added before it is promoted to green.
Rare genetic inflammatory skin disorders v1.42 RNU12 Eleanor Williams Gene: rnu12 has been classified as Amber List (Moderate Evidence).
Rare genetic inflammatory skin disorders v1.41 RNU12 Eleanor Williams Tag currently-ngs-unreportable tag was added to gene: RNU12.
Tag Q4_21_expert_review tag was added to gene: RNU12.
Tag Q4_21_rating tag was added to gene: RNU12.
Rare genetic inflammatory skin disorders v1.41 RNU12 Eleanor Williams changed review comment from: Note RNU12 has Ensembl gene ID ENSG00000276027 in GRCh38. It is not listed in OMIM. I

PMID: 34085356 (Xing et al 2021) report the analysis of 5 patients from 4 unrelated families with clinical features of CDAGS (Craniosynostosis and clavicular hypoplasia; Delayed closure of the fontanelles and cranial defects (and deafness in some patients); Anal anomalies; Genitourinary malformations; and Skin eruption, including porokeratosis). WES and Sanger sequencing was used to identify rare biallelic variants in RNU12. All affected individuals were compound heterozygous, with all 5 patients sharing NC_000022.10:g.43011402C>T, which alters a highly conserved nucleotide. Each individual also carried another variant (4 different variants) in RNU12 thought to disrupt the secondary structure or the Sm binding site of the RNU12 snRNA. All 5 individuals were reported to have skin anomalies; erythematous cutaneous eruption consistent with porokeratosis (1), erythematous skin eruption involving the cheeks, arms, and legs (1), porokeratosis (2 siblings), disseminated dermatosis (1 individual)
Sources: Literature; to: Note RNU12 has Ensembl gene ID ENSG00000276027 in GRCh38. It is not listed in OMIM. It encodes a small nuclear RNA.

PMID: 34085356 (Xing et al 2021) report the analysis of 5 patients from 4 unrelated families with clinical features of CDAGS (Craniosynostosis and clavicular hypoplasia; Delayed closure of the fontanelles and cranial defects (and deafness in some patients); Anal anomalies; Genitourinary malformations; and Skin eruption, including porokeratosis). WES and Sanger sequencing was used to identify rare biallelic variants in RNU12. All affected individuals were compound heterozygous, with all 5 patients sharing NC_000022.10:g.43011402C>T, which alters a highly conserved nucleotide. Each individual also carried another variant (4 different variants) in RNU12 thought to disrupt the secondary structure or the Sm binding site of the RNU12 snRNA. All 5 individuals were reported to have skin anomalies; erythematous cutaneous eruption consistent with porokeratosis (1), erythematous skin eruption involving the cheeks, arms, and legs (1), porokeratosis (2 siblings), disseminated dermatosis (1 individual)
Sources: Literature
Rare genetic inflammatory skin disorders v1.41 RNU12 Eleanor Williams gene: RNU12 was added
gene: RNU12 was added to Rare genetic inflammatory skin disorders. Sources: Literature
Mode of inheritance for gene: RNU12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNU12 were set to 34085356
Phenotypes for gene: RNU12 were set to porokeratosis; erythematous cutaneous eruption
Review for gene: RNU12 was set to GREEN
Added comment: Note RNU12 has Ensembl gene ID ENSG00000276027 in GRCh38. It is not listed in OMIM. I

PMID: 34085356 (Xing et al 2021) report the analysis of 5 patients from 4 unrelated families with clinical features of CDAGS (Craniosynostosis and clavicular hypoplasia; Delayed closure of the fontanelles and cranial defects (and deafness in some patients); Anal anomalies; Genitourinary malformations; and Skin eruption, including porokeratosis). WES and Sanger sequencing was used to identify rare biallelic variants in RNU12. All affected individuals were compound heterozygous, with all 5 patients sharing NC_000022.10:g.43011402C>T, which alters a highly conserved nucleotide. Each individual also carried another variant (4 different variants) in RNU12 thought to disrupt the secondary structure or the Sm binding site of the RNU12 snRNA. All 5 individuals were reported to have skin anomalies; erythematous cutaneous eruption consistent with porokeratosis (1), erythematous skin eruption involving the cheeks, arms, and legs (1), porokeratosis (2 siblings), disseminated dermatosis (1 individual)
Sources: Literature
Childhood onset dystonia, chorea or related movement disorder v1.189 HTT Arina Puzriakova Publications for gene: HTT were set to
Intellectual disability v3.1441 HTT Arina Puzriakova Publications for gene: HTT were set to 26740508; 27329733
Childhood onset dystonia, chorea or related movement disorder v1.188 HTT Arina Puzriakova Added comment: Comment on mode of inheritance: Biallelic SNVs have been reported for Lopes-Maciel-Rodan syndrome
Childhood onset dystonia, chorea or related movement disorder v1.188 HTT Arina Puzriakova Mode of inheritance for gene: HTT was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal
Childhood onset dystonia, chorea or related movement disorder v1.187 HTT Arina Puzriakova Classified gene: HTT as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v1.187 HTT Arina Puzriakova Gene: htt has been classified as Amber List (Moderate Evidence).
Adult onset leukodystrophy v1.35 EARS2 Ivone Leong Tag Q4_21_expert_review tag was added to gene: EARS2.
Childhood onset dystonia, chorea or related movement disorder v1.186 HTT Arina Puzriakova reviewed gene: HTT: Rating: ; Mode of pathogenicity: None; Publications: 26740508, 27329733, 33432339; Phenotypes: Lopes-Maciel-Rodan syndrome, OMIM:617435; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Childhood onset dystonia, chorea or related movement disorder v1.186 HTT Arina Puzriakova Tag watchlist tag was added to gene: HTT.
Adult onset leukodystrophy v1.35 CTC1 Ivone Leong Phenotypes for gene: CTC1 were changed from Cerebroretinal microangiopathy with calcifications and cysts, 612199 to Cerebroretinal microangiopathy with calcifications and cysts, OMIM:612199
Adult onset leukodystrophy v1.34 CTC1 Ivone Leong Publications for gene: CTC1 were set to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset dystonia, chorea or related movement disorder v1.150 HTT Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Adult onset dystonia, chorea or related movement disorder v1.150 HTT Arina Puzriakova Mode of inheritance for gene: HTT was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Other
Hereditary ataxia with onset in adulthood v2.117 HTT Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism. Biallelic variants not relevant to this panel.
Hereditary ataxia with onset in adulthood v2.117 HTT Arina Puzriakova Mode of inheritance for gene: HTT was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to Other
Mitochondrial disorders v2.57 HTT Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Mitochondrial disorders v2.57 HTT Arina Puzriakova Mode of inheritance for gene: HTT was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Other
Possible mitochondrial disorder - nuclear genes v1.55 HTT Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Possible mitochondrial disorder - nuclear genes v1.55 HTT Arina Puzriakova Mode of inheritance for gene: HTT was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Other
Adult onset neurodegenerative disorder v2.235 HTT Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Adult onset neurodegenerative disorder v2.235 HTT Arina Puzriakova Mode of inheritance for gene: HTT was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Other
Paroxysmal central nervous system disorders v1.30 HTT Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Paroxysmal central nervous system disorders v1.30 HTT Arina Puzriakova Mode of inheritance for gene: HTT was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Other
Structural basal ganglia disorders v1.25 HTT Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Structural basal ganglia disorders v1.25 HTT Arina Puzriakova Mode of inheritance for gene: HTT was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Other
Brain channelopathy v1.69 HTT Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Brain channelopathy v1.69 HTT Arina Puzriakova Mode of inheritance for gene: HTT was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to Other
Parkinson Disease and Complex Parkinsonism v1.88 HTT Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Parkinson Disease and Complex Parkinsonism v1.88 HTT Arina Puzriakova Mode of inheritance for gene: HTT was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Other
Adult onset leukodystrophy v1.33 COL4A2 Ivone Leong Tag Q4_21_expert_review tag was added to gene: COL4A2.
Tag Q4_21_phenotype tag was added to gene: COL4A2.
Early onset or syndromic epilepsy v2.463 COLGALT1 Ivone Leong changed review comment from: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in OMIM but not Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.; to: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in OMIM but not Gene2Phenotype. There is not enough evidence to support a gene-disease association as only 2 of 3 cases had seizures.
Early onset or syndromic epilepsy v2.463 COLGALT1 Ivone Leong Tag Q4_21_rating was removed from gene: COLGALT1.
Tag watchlist tag was added to gene: COLGALT1.
Inherited white matter disorders v1.147 COLGALT1 Ivone Leong Tag Q4_21_rating was removed from gene: COLGALT1.
Inherited white matter disorders v1.147 COLGALT1 Ivone Leong Classified gene: COLGALT1 as Green List (high evidence)
Inherited white matter disorders v1.147 COLGALT1 Ivone Leong Added comment: Comment on list classification: Promoted from Amber to Green as per my review.
Inherited white matter disorders v1.147 COLGALT1 Ivone Leong Gene: colgalt1 has been classified as Green List (High Evidence).
Inherited white matter disorders v1.146 COLGALT1 Ivone Leong changed review comment from: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in OMIM but not Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.; to: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in OMIM but not Gene2Phenotype. There is enough evidence to support a gene-disease association.
Familial cerebral small vessel disease v1.13 COLGALT1 Ivone Leong Classified gene: COLGALT1 as Green List (high evidence)
Familial cerebral small vessel disease v1.13 COLGALT1 Ivone Leong Added comment: Comment on list classification: Promoted from Amber to Green as per my review.
Familial cerebral small vessel disease v1.13 COLGALT1 Ivone Leong Gene: colgalt1 has been classified as Green List (High Evidence).
Familial cerebral small vessel disease v1.12 COLGALT1 Ivone Leong Tag Q4_21_rating was removed from gene: COLGALT1.
Familial cerebral small vessel disease v1.12 COLGALT1 Ivone Leong changed review comment from: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in OMIM but not Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.; to: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in OMIM but not Gene2Phenotype. There is enough evidence to support a gene-disease association.
Familial cerebral small vessel disease v1.12 COLGALT1 Ivone Leong Entity copied from White matter disorders and cerebral calcification - narrow panel v1.216
Familial cerebral small vessel disease v1.12 COLGALT1 Ivone Leong gene: COLGALT1 was added
gene: COLGALT1 was added to Familial cerebral small vessel disease. Sources: Expert Review Amber,Literature
Q4_21_rating tags were added to gene: COLGALT1.
Mode of inheritance for gene: COLGALT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COLGALT1 were set to 30412317; 33709034; 31759980
Phenotypes for gene: COLGALT1 were set to Brain small vessel disease 3, OMIM:618360
Early onset or syndromic epilepsy v2.463 COLGALT1 Ivone Leong Entity copied from White matter disorders and cerebral calcification - narrow panel v1.216
Early onset or syndromic epilepsy v2.463 COLGALT1 Ivone Leong gene: COLGALT1 was added
gene: COLGALT1 was added to Genetic epilepsy syndromes. Sources: Expert Review Amber,Literature
Q4_21_rating tags were added to gene: COLGALT1.
Mode of inheritance for gene: COLGALT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COLGALT1 were set to 30412317; 33709034; 31759980
Phenotypes for gene: COLGALT1 were set to Brain small vessel disease 3, OMIM:618360
Inherited white matter disorders v1.146 COLGALT1 Ivone Leong Entity copied from White matter disorders and cerebral calcification - narrow panel v1.216
Inherited white matter disorders v1.146 COLGALT1 Ivone Leong gene: COLGALT1 was added
gene: COLGALT1 was added to Inherited white matter disorders. Sources: Literature,Expert Review Amber
Q4_21_rating tags were added to gene: COLGALT1.
Mode of inheritance for gene: COLGALT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COLGALT1 were set to 30412317; 33709034; 31759980
Phenotypes for gene: COLGALT1 were set to Brain small vessel disease 3, OMIM:618360
White matter disorders and cerebral calcification - narrow panel v1.216 COLGALT1 Ivone Leong Phenotypes for gene: COLGALT1 were changed from Brain small vessel disease 3 MIM#618360 to Brain small vessel disease 3, OMIM:618360
White matter disorders and cerebral calcification - narrow panel v1.215 COLGALT1 Ivone Leong Classified gene: COLGALT1 as Amber List (moderate evidence)
White matter disorders and cerebral calcification - narrow panel v1.215 COLGALT1 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in OMIM but not Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
White matter disorders and cerebral calcification - narrow panel v1.215 COLGALT1 Ivone Leong Gene: colgalt1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v3.1440 HTT Arina Puzriakova Phenotypes for gene: HTT were changed from Lopes-Maciel-Rodan syndrome, 617435; LOMARS; Intellectual disability to Lopes-Maciel-Rodan syndrome, OMIM:617435; LOMARS
Childhood onset dystonia, chorea or related movement disorder v1.186 HTT Arina Puzriakova Phenotypes for gene: HTT were changed from Huntington disease, 143100 to Lopes-Maciel-Rodan syndrome, OMIM:617435; LOMARS
Adult onset dystonia, chorea or related movement disorder v1.149 HTT Arina Puzriakova Phenotypes for gene: HTT were changed from Huntington disease to Huntington disease, OMIM:143100
Adult onset dystonia, chorea or related movement disorder v1.148 HTT Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: HTT.
Tag currently-ngs-unreportable tag was added to gene: HTT.
Hereditary ataxia with onset in adulthood v2.116 HTT Arina Puzriakova Phenotypes for gene: HTT were changed from Huntington disease 143100; Lopes-Maciel-Rodan syndrome, 617432 to Huntington disease, OMIM:143100
Mitochondrial disorders v2.56 HTT Arina Puzriakova Phenotypes for gene: HTT were changed from Huntington disease, 143100 to Huntington disease, OMIM:143100
Mitochondrial disorders v2.55 HTT Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: HTT.
Tag currently-ngs-unreportable tag was added to gene: HTT.
Possible mitochondrial disorder - nuclear genes v1.54 HTT Arina Puzriakova Phenotypes for gene: HTT were changed from Huntington disease, 143100 to Huntington disease, OMIM:143100
Possible mitochondrial disorder - nuclear genes v1.53 HTT Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: HTT.
Tag currently-ngs-unreportable tag was added to gene: HTT.
Adult onset neurodegenerative disorder v2.234 HTT Arina Puzriakova Phenotypes for gene: HTT were changed from Huntington disease 143100; Huntingtons disease (HD) to Huntington disease, OMIM:143100
Paroxysmal central nervous system disorders v1.29 HTT Arina Puzriakova Phenotypes for gene: HTT were changed from Huntington disease, 143100 to Huntington disease, OMIM:143100
Paroxysmal central nervous system disorders v1.28 HTT Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: HTT.
Tag currently-ngs-unreportable tag was added to gene: HTT.
Structural basal ganglia disorders v1.24 HTT Arina Puzriakova Phenotypes for gene: HTT were changed from Huntington disease 143100 to Huntington disease, OMIM:143100
Brain channelopathy v1.68 HTT Arina Puzriakova Phenotypes for gene: HTT were changed from Huntington disease 143100 to Huntington disease, OMIM:143100
Parkinson Disease and Complex Parkinsonism v1.87 HTT Arina Puzriakova Phenotypes for gene: HTT were changed from Huntingtons disease (HD) to Huntington disease, OMIM:143100
Adult onset dystonia, chorea or related movement disorder v1.148 HTT_CAG Arina Puzriakova Phenotypes for STR: HTT_CAG were changed from Huntington disease 143100 to Huntington disease, OMIM:143100
Hereditary ataxia with onset in adulthood v2.115 HTT_CAG Arina Puzriakova Phenotypes for STR: HTT_CAG were changed from Huntington disease 143100 to Huntington disease, OMIM:143100
Adult onset neurodegenerative disorder v2.233 HTT_CAG Arina Puzriakova Phenotypes for STR: HTT_CAG were changed from Huntington disease 143100 to Huntington disease, OMIM:143100
Adult onset hereditary spastic paraplegia v1.80 HTT_CAG Arina Puzriakova Phenotypes for STR: HTT_CAG were changed from Huntington disease 143100 to Huntington disease, OMIM:143100
Childhood onset hereditary spastic paraplegia v2.94 HTT_CAG Arina Puzriakova Phenotypes for STR: HTT_CAG were changed from Huntington disease 143100 to Huntington disease, OMIM:143100
Hereditary spastic paraplegia v1.268 HTT_CAG Arina Puzriakova Phenotypes for STR: HTT_CAG were changed from Huntington disease 143100 to Huntington disease, OMIM:143100
Structural basal ganglia disorders v1.23 HTT_CAG Arina Puzriakova Phenotypes for STR: HTT_CAG were changed from Huntington disease 143100 to Huntington disease, OMIM:143100
Hereditary ataxia v1.271 HTT_CAG Arina Puzriakova Phenotypes for STR: HTT_CAG were changed from Huntington disease 143100 to Huntington disease, OMIM:143100
Ataxia and cerebellar anomalies - narrow panel v2.265 HTT_CAG Arina Puzriakova Phenotypes for STR: HTT_CAG were changed from Huntington disease 143100 to Huntington disease, OMIM:143100
Brain channelopathy v1.67 HTT_CAG Arina Puzriakova Phenotypes for STR: HTT_CAG were changed from Huntington disease 143100 to Huntington disease, OMIM:143100
White matter disorders and cerebral calcification - narrow panel v1.214 COLGALT1 Ivone Leong Tag Q4_21_rating tag was added to gene: COLGALT1.
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.62 HTT_CAG Arina Puzriakova Phenotypes for STR: HTT_CAG were changed from Huntington disease 143100 to Huntington disease, OMIM:143100
Parkinson Disease and Complex Parkinsonism v1.86 HTT_CAG Arina Puzriakova Phenotypes for STR: HTT_CAG were changed from Huntington disease 143100 to Huntington disease, OMIM:143100
Hereditary neuropathy v1.424 FMR1_CGG Arina Puzriakova Phenotypes for STR: FMR1_CGG were changed from Fragile X syndrome 300624; Late onset tremor, ataxia, parkinsonism, sensory axonal neuropathy, middle cerebellar peduncle changes on MRI to Fragile X syndrome, OMIM:300624; Fragile X tremor/ataxia syndrome, OMIM:300623
Hereditary neuropathy v1.423 FMR1_CGG Arina Puzriakova Tag currently-ngs-unreportable was removed from STR: FMR1_CGG.
Intellectual disability v3.1439 FMR1_CGG Arina Puzriakova Phenotypes for STR: FMR1_CGG were changed from Fragile X syndrome 300624 to Fragile X syndrome, OMIM:300624; Fragile X tremor/ataxia syndrome, OMIM:300623
Intellectual disability v3.1438 FMR1_CGG Arina Puzriakova Tag currently-ngs-unreportable was removed from STR: FMR1_CGG.
Hereditary ataxia with onset in adulthood v2.114 FMR1_CGG Arina Puzriakova Phenotypes for STR: FMR1_CGG were changed from Fragile X syndrome, 300624 to Fragile X tremor/ataxia syndrome, OMIM:300623
Hereditary ataxia v1.270 FMR1_CGG Arina Puzriakova Phenotypes for STR: FMR1_CGG were changed from Fragile X syndrome 300624 to Fragile X tremor/ataxia syndrome, OMIM:300623
Rare syndromic craniosynostosis or isolated multisuture synostosis v2.58 SMAD3 Eleanor Williams Classified gene: SMAD3 as Amber List (moderate evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v2.58 SMAD3 Eleanor Williams Added comment: Comment on list classification: On advice from Genomics England clinical team, promoting this gene from grey to amber. The number of cases with a craniosynostosis phenotype is borderline so rating as amber for now. Only 1 biallelic case reported so far so keeping the mode of inheritance as monoallelic.
Rare syndromic craniosynostosis or isolated multisuture synostosis v2.58 SMAD3 Eleanor Williams Gene: smad3 has been classified as Amber List (Moderate Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v2.57 SMAD3 Eleanor Williams Phenotypes for gene: SMAD3 were changed from Loeys-Dietz syndrome 3, MIM# 613795 to Loeys-Dietz syndrome 3, OMIM:613795
Rare syndromic craniosynostosis or isolated multisuture synostosis v2.56 SMAD3 Eleanor Williams Publications for gene: SMAD3 were set to 20301312; 29392890
Primary ovarian insufficiency v1.55 FMR1 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Primary ovarian insufficiency v1.55 FMR1 Arina Puzriakova 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 Other
Ataxia and cerebellar anomalies - narrow panel v2.264 FMR1 Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: FMR1.
Intellectual disability v3.1438 FMR1 Arina Puzriakova Phenotypes for gene: FMR1 were changed from Fragile X syndrome, 300624Fragile X tremor/ataxia syndrome, 300623Premature ovarian failure 1, 311360; PREMATURE OVARIAN FAILURE SYNDROME TYPE 1 (POF1) to Fragile X syndrome, OMIM:300624; Fragile X tremor/ataxia syndrome, OMIM:300623
Intellectual disability v3.1437 FMR1 Arina Puzriakova Tag currently-ngs-unreportable was removed from gene: FMR1.
Hereditary ataxia v1.269 FMR1 Arina Puzriakova Phenotypes for gene: FMR1 were changed from FMR1-related disorders include fragile X syndrome, fragile X-associated tremor/ataxia syndrome (FXTAS), and FMR1-related premature ovarian insufficiency (POI); FragileXtremor/ataxiasyndrome,300623; males with a tremor phenotype to Fragile X tremor/ataxia syndrome, OMIM:300623
Ataxia and cerebellar anomalies - narrow panel v2.264 FMR1 Arina Puzriakova Phenotypes for gene: FMR1 were changed from FMR1-related disorders include fragile X syndrome, fragile X-associated tremor/ataxia syndrome (FXTAS), and FMR1-related premature ovarian insufficiency (POI); males with a tremor phenotype; FragileXtremor/ataxiasyndrome,300623 to Fragile X tremor/ataxia syndrome, OMIM:300623
Hereditary ataxia with onset in adulthood v2.113 FMR1 Arina Puzriakova Phenotypes for gene: FMR1 were changed from FragileXtremor/ataxiasyndrome,300623; Fragile X tremor/ataxia syndrome; FMR1-related disorders include fragile X syndrome, fragile X-associated tremor/ataxia syndrome (FXTAS), and FMR1-related premature ovarian insufficiency (POI); males with a tremor phenotype to Fragile X tremor/ataxia syndrome, OMIM:300623
Fetal anomalies v1.808 FMR1 Arina Puzriakova Phenotypes for gene: FMR1 were changed from FRAGILE X SYNDROME; FRAGILE X TREMOR/ATAXIA SYNDROME; PREMATURE OVARIAN FAILURE SYNDROME TYPE 1 to Fragile X syndrome, OMIM:300624; Fragile X tremor/ataxia syndrome, OMIM:300623
Adult onset neurodegenerative disorder v2.232 FMR1 Arina Puzriakova Phenotypes for gene: FMR1 were changed from FMR1-related disorders include fragile X syndrome, fragile X-associated tremor/ataxia syndrome (FXTAS), and FMR1-related premature ovarian insufficiency (POI); males with a tremor phenotype; FragileXtremor/ataxiasyndrome,300623 to Fragile X syndrome, OMIM:300624; Fragile X tremor/ataxia syndrome, OMIM:300623
Hydrocephalus v2.124 FMR1 Arina Puzriakova Tag currently-ngs-unreportable was removed from gene: FMR1.
Hydrocephalus v2.124 FMR1 Arina Puzriakova Phenotypes for gene: FMR1 were changed from Fragile X syndrome 300624 to Fragile X syndrome, OMIM:300624
Hydrocephalus v2.123 FMR1 Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: FMR1.
Tag currently-ngs-unreportable tag was added to gene: FMR1.
Primary ovarian insufficiency v1.54 FMR1_CGG Arina Puzriakova Phenotypes for STR: FMR1_CGG were changed from Fragile X syndrome 300624 to Premature ovarian failure 1, OMIM:311360
Primary ovarian insufficiency v1.53 FMR1 Arina Puzriakova Phenotypes for gene: FMR1 were changed from Fragile X syndrome, 300624; Fragile X tremor ataxia syndrome, 300623; Premature ovarian failure 1, 311360; Premature Ovarian Insufficiency to Premature ovarian failure 1, OMIM:311360
Non-syndromic familial congenital anorectal malformations v1.8 MED12 Eleanor Williams Added comment: Comment on mode of inheritance: Updating the mode of inheritance to X-linked: hemizygous mutation in males, monallelic mutations in females after advice from the Genomics England clinical team. There are 5 reported relevant cases in females.
Non-syndromic familial congenital anorectal malformations v1.8 MED12 Eleanor Williams Mode of inheritance for gene: MED12 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Skeletal dysplasia v2.154 ZNF687 Eleanor Williams Phenotypes for gene: ZNF687 were changed from Paget Disease of Bone with associated Giant Cell Tumour. to Paget disease of bone 6, OMIM:616833
Skeletal dysplasia v2.153 ZNF687 Eleanor Williams Publications for gene: ZNF687 were set to PMID: 29493781, PMID: 28968976, PMID: 26849110
Skeletal dysplasia v2.152 ZNF687 Eleanor Williams Classified gene: ZNF687 as Amber List (moderate evidence)
Skeletal dysplasia v2.152 ZNF687 Eleanor Williams Added comment: Comment on list classification: Promoting from grey to amber but with a recommendation for a green rating following GMS review.
Skeletal dysplasia v2.152 ZNF687 Eleanor Williams Gene: znf687 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.151 ZNF687 Eleanor Williams Tag Q4_21_rating tag was added to gene: ZNF687.
Skeletal dysplasia v2.151 ZNF687 Eleanor Williams reviewed gene: ZNF687: Rating: GREEN; Mode of pathogenicity: None; Publications: 29493781, 26849110; Phenotypes: Paget disease of bone 6, OMIM:616833; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary spastic paraplegia v1.267 KIDINS220 Sarah Leigh Phenotypes for gene: KIDINS220 were changed from Spastic paraplegia, intellectual disability, nystagmus, and obesity 617296 to Spastic paraplegia, intellectual disability, nystagmus, and obesity OMIM:617296
Hereditary spastic paraplegia v1.266 KIDINS220 Sarah Leigh Publications for gene: KIDINS220 were set to 27005418; 29667355; 31630374
COVID-19 research v1.85 LZTFL1 Sarah Leigh Classified gene: LZTFL1 as Red List (low evidence)
COVID-19 research v1.85 LZTFL1 Sarah Leigh Gene: lztfl1 has been classified as Red List (Low Evidence).
COVID-19 research v1.84 LZTFL1 Sarah Leigh reviewed gene: LZTFL1: 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: ; Mode of inheritance: None
COVID-19 research v1.84 LZTFL1 Sarah Leigh Phenotypes for gene: LZTFL1 were changed from Visceral Heterotaxy; Bardet-Biedl Syndrome 17 to Bardet-Biedl syndrome 17 OMIM:615994
COVID-19 research v1.83 LZTFL1 Sarah Leigh Publications for gene: LZTFL1 were set to 22510444; 23692385
COVID-19 research v1.82 LZTFL1 Sarah Leigh Entity copied from Primary ciliary disorders v1.36
COVID-19 research v1.82 LZTFL1 Sarah Leigh gene: LZTFL1 was added
gene: LZTFL1 was added to COVID-19 research. Sources: UKGTN,Expert Review Amber
watchlist tags were added to gene: LZTFL1.
Mode of inheritance for gene: LZTFL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LZTFL1 were set to 22510444; 23692385
Phenotypes for gene: LZTFL1 were set to Visceral Heterotaxy; Bardet-Biedl Syndrome 17
Penetrance for gene: LZTFL1 were set to Complete
Primary ciliary disorders v1.36 LZTFL1 Sarah Leigh Phenotypes for gene: LZTFL1 were changed from Visceral Heterotaxy; Bardet-Biedl Syndrome 17 to Visceral Heterotaxy; Bardet-Biedl Syndrome 17
Publications for gene: LZTFL1 were updated from 22510444; 23692385 to 22510444; 23692385
Intellectual disability v3.1437 ATXN1 Arina Puzriakova Phenotypes for gene: ATXN1 were changed from Spinocerebellar ataxia 1 164400 to Spinocerebellar ataxia 1, OMIM:164400
Intellectual disability v3.1436 ATXN1 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Intellectual disability v3.1436 ATXN1 Arina Puzriakova Mode of inheritance for gene: ATXN1 was changed from BIALLELIC, autosomal or pseudoautosomal to Other
Adult onset neurodegenerative disorder v2.231 ATXN1 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Adult onset neurodegenerative disorder v2.231 ATXN1 Arina Puzriakova Mode of inheritance for gene: ATXN1 was changed from Unknown to Other
Hereditary ataxia v1.268 ATXN1 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Hereditary ataxia v1.268 ATXN1 Arina Puzriakova Mode of inheritance for gene: ATXN1 was changed from to Other
Ataxia and cerebellar anomalies - narrow panel v2.263 ATXN1 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Ataxia and cerebellar anomalies - narrow panel v2.263 ATXN1 Arina Puzriakova Mode of inheritance for gene: ATXN1 was changed from Unknown to Other
Hereditary ataxia with onset in adulthood v2.112 ATXN1 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Hereditary ataxia with onset in adulthood v2.112 ATXN1 Arina Puzriakova Mode of inheritance for gene: ATXN1 was changed from Unknown to Other
Adult onset dystonia, chorea or related movement disorder v1.147 ATXN1 Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: ATXN1.
Tag currently-ngs-unreportable tag was added to gene: ATXN1.
Adult onset dystonia, chorea or related movement disorder v1.147 ATXN1 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Adult onset dystonia, chorea or related movement disorder v1.147 ATXN1 Arina Puzriakova Mode of inheritance for gene: ATXN1 was changed from to Other
Childhood onset dystonia, chorea or related movement disorder v1.185 ATXN1 Arina Puzriakova Mode of pathogenicity for gene: ATXN1 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
Childhood onset dystonia, chorea or related movement disorder v1.184 ATXN1 Arina Puzriakova Phenotypes for gene: ATXN1 were changed from Spinocerebellar ataxia 1, 164400 to Spinocerebellar ataxia 1, OMIM:164400
Adult onset dystonia, chorea or related movement disorder v1.146 ATXN1 Arina Puzriakova Phenotypes for gene: ATXN1 were changed from to Spinocerebellar ataxia 1, OMIM:164400
Hereditary ataxia with onset in adulthood v2.111 ATXN1 Arina Puzriakova Phenotypes for gene: ATXN1 were changed from Spinocerebellar ataxia 1, 164400; Spinocerebellarataxia1,164400 to Spinocerebellar ataxia 1, OMIM:164400
Adult onset neurodegenerative disorder v2.230 ATXN1 Arina Puzriakova Phenotypes for gene: ATXN1 were changed from Spinocerebellarataxia1,164400 to Spinocerebellar ataxia 1, OMIM:164400
Hereditary ataxia v1.267 ATXN1 Arina Puzriakova Phenotypes for gene: ATXN1 were changed from Spinocerebellarataxia1,164400 to Spinocerebellar ataxia 1, OMIM:164400
Ataxia and cerebellar anomalies - narrow panel v2.262 ATXN1 Arina Puzriakova Phenotypes for gene: ATXN1 were changed from Spinocerebellarataxia1,164400 to Spinocerebellar ataxia 1, OMIM:164400
Ataxia and cerebellar anomalies - narrow panel v2.261 ATXN1 Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: ATXN1.
Tag currently-ngs-unreportable tag was added to gene: ATXN1.
Adult onset dystonia, chorea or related movement disorder v1.145 ATXN1_CAG Arina Puzriakova Phenotypes for STR: ATXN1_CAG were changed from Spinocerebellar ataxia 1 164400 to Spinocerebellar ataxia 1, OMIM:164400
Adult onset dystonia, chorea or related movement disorder v1.144 ATXN1_CAG Arina Puzriakova Tag watchlist tag was added to STR: ATXN1_CAG.
Intellectual disability v3.1435 ATXN1_CAG Arina Puzriakova Phenotypes for STR: ATXN1_CAG were changed from Spinocerebellar ataxia 1 164400 to Spinocerebellar ataxia 1, OMIM:164400
Hereditary ataxia with onset in adulthood v2.110 ATXN1_CAG Arina Puzriakova Phenotypes for STR: ATXN1_CAG were changed from Spinocerebellar ataxia 1 164400 to Spinocerebellar ataxia 1, OMIM:164400
Hereditary neuropathy v1.423 ATXN1_CAG Arina Puzriakova Phenotypes for STR: ATXN1_CAG were changed from Spinocerebellar ataxia 1 164400 to Spinocerebellar ataxia 1, OMIM:164400
Adult onset neurodegenerative disorder v2.229 ATXN1_CAG Arina Puzriakova Phenotypes for STR: ATXN1_CAG were changed from Spinocerebellar ataxia 1 164400 to Spinocerebellar ataxia 1, OMIM:164400
Adult onset neurodegenerative disorder v2.228 ATXN1_CAG Arina Puzriakova Tag watchlist tag was added to STR: ATXN1_CAG.
Adult onset hereditary spastic paraplegia v1.79 ATXN1_CAG Arina Puzriakova Phenotypes for STR: ATXN1_CAG were changed from Spinocerebellar ataxia 1 164400 to Spinocerebellar ataxia 1, OMIM:164400
Childhood onset hereditary spastic paraplegia v2.93 ATXN1_CAG Arina Puzriakova Phenotypes for STR: ATXN1_CAG were changed from Spinocerebellar ataxia 1 164400 to Spinocerebellar ataxia 1, OMIM:164400
Hereditary spastic paraplegia v1.265 ATXN1_CAG Arina Puzriakova Phenotypes for STR: ATXN1_CAG were changed from Spinocerebellar ataxia 1 164400 to Spinocerebellar ataxia 1, OMIM:164400
Hereditary ataxia v1.266 ATXN1_CAG Arina Puzriakova Phenotypes for STR: ATXN1_CAG were changed from Spinocerebellar ataxia 1 164400 to Spinocerebellar ataxia 1, OMIM:164400
Ataxia and cerebellar anomalies - narrow panel v2.261 ATXN1_CAG Arina Puzriakova Phenotypes for STR: ATXN1_CAG were changed from Spinocerebellar ataxia 1 164400 to Spinocerebellar ataxia 1, OMIM:164400
Ataxia and cerebellar anomalies - narrow panel v2.260 ATXN1_CAG Arina Puzriakova Tag watchlist tag was added to STR: ATXN1_CAG.
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.61 ATXN1_CAG Arina Puzriakova Phenotypes for STR: ATXN1_CAG were changed from Spinocerebellar ataxia 1 164400 to Spinocerebellar ataxia 1, OMIM:164400
Parkinson Disease and Complex Parkinsonism v1.85 ATXN1_CAG Arina Puzriakova Phenotypes for STR: ATXN1_CAG were changed from Spinocerebellar ataxia 1 164400 to Spinocerebellar ataxia 1, OMIM:164400
Intellectual disability v3.1434 JPH3 Arina Puzriakova Phenotypes for gene: JPH3 were changed from Intellectual disability; dystonia to Neurodevelopmental disorder, MONDO:0700092; Paroxysmal dystonia, MONDO:0016058
Adult onset dystonia, chorea or related movement disorder v1.144 JPH3 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Adult onset dystonia, chorea or related movement disorder v1.144 JPH3 Arina Puzriakova Mode of inheritance for gene: JPH3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to Other
Adult onset neurodegenerative disorder v2.228 JPH3 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Adult onset neurodegenerative disorder v2.228 JPH3 Arina Puzriakova Mode of inheritance for gene: JPH3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to Other
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.60 JPH3 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.60 JPH3 Arina Puzriakova Mode of inheritance for gene: JPH3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to Other
Parkinson Disease and Complex Parkinsonism v1.84 JPH3 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Parkinson Disease and Complex Parkinsonism v1.84 JPH3 Arina Puzriakova Mode of inheritance for gene: JPH3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to Other
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.59 JPH3 Arina Puzriakova Phenotypes for gene: JPH3 were changed from Huntington disease-like 2 606438 to Huntington disease-like 2, OMIM:606438
Adult onset neurodegenerative disorder v2.227 JPH3 Arina Puzriakova Phenotypes for gene: JPH3 were changed from Huntington disease-like 2 606438 to Huntington disease-like 2, OMIM:606438
Adult onset dystonia, chorea or related movement disorder v1.143 JPH3 Arina Puzriakova Phenotypes for gene: JPH3 were changed from Huntington disease-like 2 to Huntington disease-like 2, OMIM:606438
Parkinson Disease and Complex Parkinsonism v1.83 JPH3 Arina Puzriakova Phenotypes for gene: JPH3 were changed from Huntington disease-like 2 606438 to Huntington disease-like 2, OMIM:606438
Adult onset dystonia, chorea or related movement disorder v1.142 JPH3_CTG Arina Puzriakova Phenotypes for STR: JPH3_CTG were changed from Huntington disease-like 2 606438 to Huntington disease-like 2, OMIM:606438
Adult onset neurodegenerative disorder v2.226 JPH3_CTG Arina Puzriakova Phenotypes for STR: JPH3_CTG were changed from Huntington disease-like 2 606438 to Huntington disease-like 2, OMIM:606438
Adult onset neurodegenerative disorder v2.225 JPH3_CTG Arina Puzriakova Tag watchlist tag was added to STR: JPH3_CTG.
Early onset dystonia v1.96 JPH3_CTG Arina Puzriakova Phenotypes for STR: JPH3_CTG were changed from Huntington disease-like 2 606438 to Huntington disease-like 2, OMIM:606438
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.58 JPH3_CTG Arina Puzriakova Phenotypes for STR: JPH3_CTG were changed from Huntington disease-like 2 606438 to Huntington disease-like 2, OMIM:606438
Parkinson Disease and Complex Parkinsonism v1.82 JPH3_CTG Arina Puzriakova Phenotypes for STR: JPH3_CTG were changed from Huntington disease-like 2 606438 to Huntington disease-like 2, OMIM:606438
Skeletal muscle channelopathy v1.36 DMPK_CTG Arina Puzriakova Tag STR tag was added to STR: DMPK_CTG.
Intellectual disability v3.1433 DMPK_CTG Arina Puzriakova Phenotypes for STR: DMPK_CTG were changed from Myotonic dystrophy 1 160900 to Myotonic dystrophy 1, OMIM:160900
Mitochondrial disorders v2.55 DMPK_CTG Arina Puzriakova Phenotypes for STR: DMPK_CTG were changed from Myotonic dystrophy 1 160900 to Myotonic dystrophy 1, OMIM:160900
Paediatric motor neuronopathies v1.71 DMPK_CTG Arina Puzriakova Phenotypes for STR: DMPK_CTG were changed from Myotonic dystrophy 1 160900 to Myotonic dystrophy 1, OMIM:160900
Likely inborn error of metabolism v2.194 DMPK_CTG Arina Puzriakova Phenotypes for STR: DMPK_CTG were changed from Myotonic dystrophy 1 160900 to Myotonic dystrophy 1, OMIM:160900
Congenital myopathy v2.67 DMPK_CTG Arina Puzriakova Phenotypes for STR: DMPK_CTG were changed from Myotonic dystrophy 1 160900 to Myotonic dystrophy 1, OMIM:160900
Congenital muscular dystrophy v2.21 DMPK_CTG Arina Puzriakova Phenotypes for STR: DMPK_CTG were changed from Myotonic dystrophy 1 160900 to Myotonic dystrophy 1, OMIM:160900
Paroxysmal central nervous system disorders v1.28 DMPK_CTG Arina Puzriakova Phenotypes for STR: DMPK_CTG were changed from Myotonic dystrophy 1 160900 to Myotonic dystrophy 1, OMIM:160900
Gastrointestinal neuromuscular disorders v1.18 DMPK_CTG Arina Puzriakova Phenotypes for STR: DMPK_CTG were changed from Myotonic dystrophy 1 160900 to Myotonic dystrophy 1, OMIM:160900
Fetal hydrops v1.42 DMPK_CTG Arina Puzriakova Phenotypes for STR: DMPK_CTG were changed from Myotonic dystrophy 1 160900 to Myotonic dystrophy 1, OMIM:160900
Skeletal Muscle Channelopathies v1.41 DMPK_CTG Arina Puzriakova Phenotypes for STR: DMPK_CTG were changed from Myotonic dystrophy 1 160900 to Myotonic dystrophy 1, OMIM:160900
Fetal anomalies v1.807 DMPK Arina Puzriakova Phenotypes for gene: DMPK were changed from DYSTROPHIA MYOTONICA TYPE 1 to Myotonic dystrophy 1, OMIM:160900
Fetal anomalies v1.806 DMPK Arina Puzriakova Mode of pathogenicity for gene: DMPK 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
Arthrogryposis v3.142 DMPK Arina Puzriakova Phenotypes for gene: DMPK were changed from Myotonic dystrophy 1 160900 to Myotonic dystrophy 1, OMIM:160900
Dilated Cardiomyopathy and conduction defects v1.74 DMPK Arina Puzriakova Phenotypes for gene: DMPK were changed from syndromic DCM to Myotonic dystrophy 1, OMIM:160900
Gastrointestinal neuromuscular disorders v1.17 DMPK Arina Puzriakova Phenotypes for gene: DMPK were changed from Myotonic dystrophy 1 160900 to Myotonic dystrophy 1, OMIM:160900
Fetal hydrops v1.41 DMPK Arina Puzriakova Phenotypes for gene: DMPK were changed from Myotonic dystrophy 1, 160900; DM1; Myotonic dystrophy, congenital onset associated with a high triplet repeat number to Myotonic dystrophy 1, OMIM:160900
Congenital myopathy v2.66 DMPK Arina Puzriakova Phenotypes for gene: DMPK were changed from Myotonic dystrophy 1 160900 to Myotonic dystrophy 1, OMIM:160900
Skeletal muscle channelopathy v1.36 DMPK Arina Puzriakova Phenotypes for gene: DMPK were changed from Myotonic dystrophy 1, 160900 to Myotonic dystrophy 1, OMIM:160900
Intellectual disability v3.1432 DMPK Arina Puzriakova Phenotypes for gene: DMPK were changed from Myotonic dystrophy 1, 160900; DYSTROPHIA MYOTONICA TYPE 1 (DM1) to Myotonic dystrophy 1, OMIM:160900
Childhood onset dystonia, chorea or related movement disorder v1.183 DMPK Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Childhood onset dystonia, chorea or related movement disorder v1.183 DMPK Arina Puzriakova Mode of inheritance for gene: DMPK was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Other
Intellectual disability v3.1431 DMPK Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Intellectual disability v3.1431 DMPK Arina Puzriakova Mode of inheritance for gene: DMPK was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Other
DDG2P v2.53 DMPK Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism. MOI should be changed to 'Other' to maintain consistency with other panels
DDG2P v2.53 DMPK Arina Puzriakova Mode of inheritance for gene: DMPK was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
DDG2P v2.52 DMPK Arina Puzriakova Tag Q3_21_MOI tag was added to gene: DMPK.
Paediatric motor neuronopathies v1.70 DMPK Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Paediatric motor neuronopathies v1.70 DMPK Arina Puzriakova Mode of inheritance for gene: DMPK was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to Other
Fetal anomalies v1.805 DMPK Arina Puzriakova Tag Q3_21_MOI tag was added to gene: DMPK.
Fetal anomalies v1.805 DMPK Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism. MOI should be changed to 'Other' to maintain consistency with other panels
Fetal anomalies v1.805 DMPK Arina Puzriakova Mode of inheritance for gene: DMPK was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Skeletal muscle channelopathy v1.35 DMPK Arina Puzriakova Mode of pathogenicity for gene: DMPK 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
Skeletal muscle channelopathy v1.34 DMPK Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Skeletal muscle channelopathy v1.34 DMPK Arina Puzriakova Mode of inheritance for gene: DMPK was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Other
Skeletal muscle channelopathy v1.33 DMPK Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: DMPK.
Tag currently-ngs-unreportable tag was added to gene: DMPK.
Congenital myopathy v2.65 DMPK Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Congenital myopathy v2.65 DMPK Arina Puzriakova Mode of inheritance for gene: DMPK was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Other
Arthrogryposis v3.141 DMPK Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Arthrogryposis v3.141 DMPK Arina Puzriakova Mode of inheritance for gene: DMPK was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to Other
Arthrogryposis v3.140 DMPK Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: DMPK.
Tag currently-ngs-unreportable tag was added to gene: DMPK.
Paroxysmal central nervous system disorders v1.27 DMPK Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Paroxysmal central nervous system disorders v1.27 DMPK Arina Puzriakova Mode of inheritance for gene: DMPK was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Other
Paroxysmal central nervous system disorders v1.26 DMPK Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: DMPK.
Tag currently-ngs-unreportable tag was added to gene: DMPK.
Dilated Cardiomyopathy and conduction defects v1.73 DMPK Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Dilated Cardiomyopathy and conduction defects v1.73 DMPK Arina Puzriakova Mode of inheritance for gene: DMPK was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to Other
Dilated Cardiomyopathy and conduction defects v1.72 DMPK Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: DMPK.
Tag currently-ngs-unreportable tag was added to gene: DMPK.
Gastrointestinal neuromuscular disorders v1.16 DMPK Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Gastrointestinal neuromuscular disorders v1.16 DMPK Arina Puzriakova Mode of inheritance for gene: DMPK was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to Other
Gastrointestinal neuromuscular disorders v1.15 DMPK Arina Puzriakova Tag currently-ngs-unreportable tag was added to gene: DMPK.
Distal myopathies v1.37 DMPK Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Distal myopathies v1.37 DMPK Arina Puzriakova Mode of inheritance for gene: DMPK was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to Other
Distal myopathies v1.36 DMPK Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: DMPK.
Tag currently-ngs-unreportable tag was added to gene: DMPK.
Fetal hydrops v1.40 DMPK Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Fetal hydrops v1.40 DMPK Arina Puzriakova Mode of inheritance for gene: DMPK was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to Other
Skeletal Muscle Channelopathies v1.40 DMPK Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Skeletal Muscle Channelopathies v1.40 DMPK Arina Puzriakova Mode of inheritance for gene: DMPK was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Other
Adult onset dystonia, chorea or related movement disorder v1.141 CSTB Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: CSTB.
Hereditary ataxia with onset in adulthood v2.109 CSTB Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: CSTB.
DDG2P v2.52 CSTB Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: CSTB.
Fetal anomalies v1.804 CSTB Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: CSTB.
Likely inborn error of metabolism v2.193 CSTB Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: CSTB.
Undiagnosed metabolic disorders v1.492 CSTB Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: CSTB.
Adult onset neurodegenerative disorder v2.225 CSTB Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: CSTB.
Paroxysmal central nervous system disorders v1.26 CSTB Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: CSTB.
Hereditary ataxia v1.265 CSTB Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: CSTB.
Fetal anomalies v1.804 CSTB Arina Puzriakova Phenotypes for gene: CSTB were changed from UNVERRICHT-LUNDBORG DISEASE to Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), OMIM:254800
Early onset or syndromic epilepsy v2.462 CSTB Arina Puzriakova Phenotypes for gene: CSTB were changed from Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), 254800 to Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), OMIM:254800
Intellectual disability v3.1430 CSTB Arina Puzriakova Phenotypes for gene: CSTB were changed from UNVERRICHT-LUNDBORG DISEASE to Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), OMIM:254800
Childhood onset dystonia, chorea or related movement disorder v1.182 CSTB Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: CSTB.
Early onset dystonia v1.95 CSTB Arina Puzriakova Phenotypes for gene: CSTB were changed from Epilepsy, progressive myoclonic 1A, 254800; microcephaly and severe dyskinesia (26843564) to Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), OMIM:254800
Early onset dystonia v1.94 CSTB Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: CSTB.
Childhood onset dystonia, chorea or related movement disorder v1.182 CSTB Arina Puzriakova reviewed gene: CSTB: Rating: ; Mode of pathogenicity: None; Publications: 26843564; Phenotypes: Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg) OMIM:254800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v2.193 CSTB Arina Puzriakova Phenotypes for gene: CSTB were changed from Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg) 254800 to Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), OMIM:254800
Undiagnosed metabolic disorders v1.492 CSTB Arina Puzriakova Phenotypes for gene: CSTB were changed from Myoclonic epilepsy of Unverricht and Lundborg (Other metabolic disorders); Intellectual disability to Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), OMIM:254800
Adult onset neurodegenerative disorder v2.225 CSTB Arina Puzriakova Phenotypes for gene: CSTB were changed from Epilepsy, progressive myoclonic 1A, 254800; Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), 254800; microcephaly and severe dyskinesia (26843564) to Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), OMIM:254800
Paroxysmal central nervous system disorders v1.26 CSTB Arina Puzriakova Mode of inheritance for gene: CSTB was changed from to BIALLELIC, autosomal or pseudoautosomal
Paroxysmal central nervous system disorders v1.25 CSTB Arina Puzriakova Phenotypes for gene: CSTB were changed from to Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), OMIM:254800
Hereditary ataxia v1.265 CSTB Arina Puzriakova Classified gene: CSTB as Green List (high evidence)
Hereditary ataxia v1.265 CSTB Arina Puzriakova Added comment: Comment on list classification: Upgraded from Red to Green as ataxia is a common part of the phenotype. This also reflects the current rating on GMS ataxia panels.
Hereditary ataxia v1.265 CSTB Arina Puzriakova Gene: cstb has been classified as Green List (High Evidence).
Hereditary ataxia v1.264 CSTB Arina Puzriakova Phenotypes for gene: CSTB were changed from Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), 254800 to Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), OMIM:254800
Ataxia and cerebellar anomalies - narrow panel v2.260 CSTB Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: CSTB.
Hereditary ataxia with onset in adulthood v2.109 CSTB Arina Puzriakova Phenotypes for gene: CSTB were changed from Progressive myoclonic epilepsy 1A, 254800; Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), 254800 to Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), OMIM:254800
Adult onset dystonia, chorea or related movement disorder v1.141 CSTB Arina Puzriakova Phenotypes for gene: CSTB were changed from microcephaly and severe dyskinesia (26843564); Epilepsy, progressive myoclonic 1A, 254800 to Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), OMIM:254800
Childhood onset dystonia, chorea or related movement disorder v1.182 CSTB_CCCCGCCCCGCG Arina Puzriakova Phenotypes for STR: CSTB_CCCCGCCCCGCG were changed from Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), 254800 to Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), OMIM:254800
Adult onset dystonia, chorea or related movement disorder v1.140 CSTB_CCCCGCCCCGCG Arina Puzriakova Phenotypes for STR: CSTB_CCCCGCCCCGCG were changed from Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg) 254800 to Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), OMIM:254800
Intellectual disability v3.1429 CSTB_CCCCGCCCCGCG Arina Puzriakova Phenotypes for STR: CSTB_CCCCGCCCCGCG were changed from Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg) 254800 to Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), OMIM:254800
Adult onset dystonia, chorea or related movement disorder v1.139 CSTB_CCCCGCCCCGCG Arina Puzriakova Tag watchlist tag was added to STR: CSTB_CCCCGCCCCGCG.
Hereditary ataxia with onset in adulthood v2.108 CSTB_CCCCGCCCCGCG Arina Puzriakova Phenotypes for STR: CSTB_CCCCGCCCCGCG were changed from Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg) 254800 to Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), OMIM:254800
Early onset or syndromic epilepsy v2.461 CSTB_CCCCGCCCCGCG Arina Puzriakova Phenotypes for STR: CSTB_CCCCGCCCCGCG were changed from Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg) 254800 to Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), OMIM:254800
Adult onset neurodegenerative disorder v2.224 CSTB_CCCCGCCCCGCG Arina Puzriakova Phenotypes for STR: CSTB_CCCCGCCCCGCG were changed from Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg) 254800 to Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), OMIM:254800
Adult onset neurodegenerative disorder v2.223 CSTB_CCCCGCCCCGCG Arina Puzriakova Tag watchlist tag was added to STR: CSTB_CCCCGCCCCGCG.
Paroxysmal central nervous system disorders v1.24 CSTB_CCCCGCCCCGCG Arina Puzriakova Phenotypes for STR: CSTB_CCCCGCCCCGCG were changed from Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg) 254800 to Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), OMIM:254800
Hereditary ataxia v1.263 CSTB_CCCCGCCCCGCG Arina Puzriakova Phenotypes for STR: CSTB_CCCCGCCCCGCG were changed from Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg) 254800 to Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), OMIM:254800
Brain channelopathy v1.66 CSTB_CCCCGCCCCGCG Arina Puzriakova Phenotypes for STR: CSTB_CCCCGCCCCGCG were changed from Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg) 254800 to Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), OMIM:254800
Skeletal muscle channelopathy v1.33 CNBP_CCTG Arina Puzriakova commented on STR: CNBP_CCTG
Skeletal muscle channelopathy v1.33 CNBP_CCTG Arina Puzriakova Tag Q4_21_expert_review tag was added to STR: CNBP_CCTG.
Fetal anomalies v1.803 CNBP_CCTG Arina Puzriakova Classified STR: CNBP_CCTG as Red List (low evidence)
Fetal anomalies v1.803 CNBP_CCTG Arina Puzriakova Added comment: Comment on list classification: There is enough evidence to support the gene-disease association but setting rating to Red as currently the performance of the pipeline for this STR is very poor as it is located in a complex locus.
Fetal anomalies v1.803 CNBP_CCTG Arina Puzriakova Str: cnbp_cctg has been classified as Red List (Low Evidence).
Fetal anomalies v1.802 CNBP_CCTG Arina Puzriakova STR: CNBP_CCTG was added
STR: CNBP_CCTG was added to Fetal anomalies. Sources: Expert Review
STR, NGS Not Validated tags were added to STR: CNBP_CCTG.
Mode of inheritance for STR: CNBP_CCTG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for STR: CNBP_CCTG were set to Myotonic dystrophy 2, OMIM:602668
Added comment: The mutation is a CCTG repeat expansion in intron 1 of the CNBP (ZNF9) gene. The range of expanded allele sizes is 75 to 11,000 CCTG repeats, whereas normal is up to 30.

The CCTG repeat tract in normal alleles typically contains one or more tetranucleotide interruptions. The sequence interruptions that are routinely found within the CCTG tracts of normal alleles are not found in sequenced pathogenic CCTG expansions of CNBP alleles. On transmission to the next generation, CNBP repeat length sometimes diminishes dramatically, without significant differences determined by the gender of the transmitting parent.
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Copied from Rhiannon Mellis (GOSH) review of gene CNBP on Fetal anomalies panel:

This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.
Sources: Expert Review
Fetal anomalies v1.801 CNBP Arina Puzriakova changed review comment from: Comment on list classification: Demoted to Red, this review is for the STR entity and not the gene entity.; to: Comment on list classification: Demoted to Red, this review is for the STR entity and not the gene entity. STR added separately.
Distal myopathies v1.36 CNBP Arina Puzriakova changed review comment from: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism; to: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism. MOI should be changed to 'Other' to maintain consistency with other panels
Distal myopathies v1.36 CNBP Arina Puzriakova Tag Q4_21_MOI tag was added to gene: CNBP.
Tag Q4_21_rating tag was added to gene: CNBP.
Distal myopathies v1.36 CNBP Arina Puzriakova Classified gene: CNBP as Green List (high evidence)
Distal myopathies v1.36 CNBP Arina Puzriakova Added comment: Comment on list classification: Should be demoted to Red at the next GMS update, this review is for the STR entity and not the gene entity.
Distal myopathies v1.36 CNBP Arina Puzriakova Gene: cnbp has been classified as Green List (High Evidence).
Distal myopathies v1.35 CNBP Arina Puzriakova Mode of inheritance for gene: CNBP was changed from Other to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.801 CNBP Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: CNBP.
Tag currently-ngs-unreportable tag was added to gene: CNBP.
Fetal anomalies v1.801 CNBP Arina Puzriakova Tag for-review was removed from gene: CNBP.
Fetal anomalies v1.801 CNBP Arina Puzriakova Classified gene: CNBP as Red List (low evidence)
Fetal anomalies v1.801 CNBP Arina Puzriakova Added comment: Comment on list classification: Demoted to Red, this review is for the STR entity and not the gene entity.
Fetal anomalies v1.801 CNBP Arina Puzriakova Gene: cnbp has been classified as Red List (Low Evidence).
Fetal anomalies v1.800 CNBP Arina Puzriakova Mode of pathogenicity for gene: CNBP was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Fetal anomalies v1.799 CNBP Arina Puzriakova Classified gene: CNBP as Red List (low evidence)
Fetal anomalies v1.799 CNBP Arina Puzriakova Gene: cnbp has been classified as Red List (Low Evidence).
Fetal anomalies v1.798 CNBP Arina Puzriakova Phenotypes for gene: CNBP were changed from Myotonic dystrophy 2, 602668 to Myotonic dystrophy 2, OMIM:602668
COVID-19 research v1.81 CNBP Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: CNBP.
Tag currently-ngs-unreportable tag was added to gene: CNBP.
Mosaic skin disorders - deep sequencing v1.9 PORCN Tom Cullup gene: PORCN was added
gene: PORCN was added to Mosaic skin disorders - deep sequencing. Sources: Other
Mode of inheritance for gene: PORCN 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: PORCN were set to 17546030
Phenotypes for gene: PORCN were set to Focal dermal hypoplasia (https://omim.org/entry/305600)
Penetrance for gene: PORCN were set to unknown
Review for gene: PORCN was set to GREEN
Added comment: Sources: Other
Skeletal muscle channelopathy v1.33 CNBP Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Skeletal muscle channelopathy v1.33 CNBP Arina Puzriakova Mode of inheritance for gene: CNBP was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Other
Paroxysmal central nervous system disorders v1.23 CNBP Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Paroxysmal central nervous system disorders v1.23 CNBP Arina Puzriakova Mode of inheritance for gene: CNBP was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to Other
Primary immunodeficiency or monogenic inflammatory bowel disease v2.485 CNBP Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Primary immunodeficiency or monogenic inflammatory bowel disease v2.485 CNBP Arina Puzriakova Mode of inheritance for gene: CNBP was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to Other
COVID-19 research v1.81 CNBP Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
COVID-19 research v1.81 CNBP Arina Puzriakova Mode of inheritance for gene: CNBP was changed from Unknown to Other
Fetal anomalies v1.797 CNBP Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Fetal anomalies v1.797 CNBP Arina Puzriakova Mode of inheritance for gene: CNBP was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Other
Distal myopathies v1.34 CNBP Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Distal myopathies v1.34 CNBP Arina Puzriakova Mode of inheritance for gene: CNBP was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to Other
Skeletal Muscle Channelopathies v1.39 CNBP Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Skeletal Muscle Channelopathies v1.39 CNBP Arina Puzriakova Mode of inheritance for gene: CNBP was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to Other
Cholestasis v1.93 FARSA Ivone Leong Classified gene: FARSA as Amber List (moderate evidence)
Cholestasis v1.93 FARSA Ivone Leong Added comment: Comment on list classification: Promoted from Red to Amber as there is now an additional case (see comment for publication).
Cholestasis v1.93 FARSA Ivone Leong Gene: farsa has been classified as Amber List (Moderate Evidence).
Cholestasis v1.92 FARSA Ivone Leong Added comment: Comment on publications: PMID:33598926 describes one other case with cholestasis
Cholestasis v1.92 FARSA Ivone Leong Publications for gene: FARSA were set to 31355908
Cholestasis v1.91 FARSA Ivone Leong Tag watchlist tag was added to gene: FARSA.
Familial pulmonary fibrosis v1.18 FARSA Ivone Leong Publications for gene: FARSA were set to 31355908
Familial pulmonary fibrosis v1.17 FARSA Ivone Leong Classified gene: FARSA as Green List (high evidence)
Familial pulmonary fibrosis v1.17 FARSA Ivone Leong Added comment: Comment on list classification: Promoted from Red to Green. There is now enough evidence to support a gene-disease association (>3 cases).
Familial pulmonary fibrosis v1.17 FARSA Ivone Leong Gene: farsa has been classified as Green List (High Evidence).
Intellectual disability v3.1428 FARSA Ivone Leong Tag Q4_21_rating tag was added to gene: FARSA.
Intellectual disability v3.1428 FARSA Ivone Leong Classified gene: FARSA as Amber List (moderate evidence)
Intellectual disability v3.1428 FARSA Ivone Leong Added comment: Comment on list classification: Promoted from Red to Amber. There is now enough evidence to support a gene-disease association (>3 cases). This gene should be rated Green at the next review.
Intellectual disability v3.1428 FARSA Ivone Leong Gene: farsa has been classified as Amber List (Moderate Evidence).
Intracerebral calcification disorders v1.32 FARSA Ivone Leong Publications for gene: FARSA were set to 31355908
Intracerebral calcification disorders v1.31 FARSA Ivone Leong Classified gene: FARSA as Green List (high evidence)
Intracerebral calcification disorders v1.31 FARSA Ivone Leong Added comment: Comment on list classification: Promoted from Red to Green. There is now enough evidence to support a gene-disease association (>3 cases).
Intracerebral calcification disorders v1.31 FARSA Ivone Leong Gene: farsa has been classified as Green List (High Evidence).
White matter disorders and cerebral calcification - narrow panel v1.214 FARSA Ivone Leong Tag Q4_21_rating tag was added to gene: FARSA.
White matter disorders and cerebral calcification - narrow panel v1.214 FARSA Ivone Leong Classified gene: FARSA as Amber List (moderate evidence)
White matter disorders and cerebral calcification - narrow panel v1.214 FARSA Ivone Leong Added comment: Comment on list classification: Promoted from Red to Amber. There is now enough evidence to support a gene-disease association (>3 cases). This gene should be rated Green at the next review.
White matter disorders and cerebral calcification - narrow panel v1.214 FARSA Ivone Leong Gene: farsa has been classified as Amber List (Moderate Evidence).
White matter disorders and cerebral calcification - narrow panel v1.213 FARSA Ivone Leong Publications for gene: FARSA were set to 31355908
Familial cerebral small vessel disease v1.11 CACNA1A Arina Puzriakova Phenotypes for gene: CACNA1A were changed from Episodic ataxia, type 2 108500; Migraine, familial hemiplegic, 1 141500 AD; Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia 141500; Spinocerebellar ataxia 6 183086 to Migraine, familial hemiplegic, 1, OMIM:141500; Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia, OMIM:141500
Intellectual disability v3.1427 CACNA1A Arina Puzriakova Phenotypes for gene: CACNA1A were changed from Epileptic encephalopathy, early infantile, 42 617106; Episodic ataxia, type 2 108500; Migraine, familial hemiplegic, 1 141500; Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia 141500; Spinocerebellar ataxia 6 183086 to Developemental and epileptic encephalopathy 42, OMIM:617106
Early onset or syndromic epilepsy v2.460 CACNA1A Arina Puzriakova Phenotypes for gene: CACNA1A were changed from Epileptic encephalopathy, early infantile, 42, 617106; Epilepsy and migraine; Absence epilepsy; Migraine, familial hemiplegic, 1, 141500; Familial hemiplegic migraine 1 (FHM) to Developmental and epileptic encephalopathy 42, OMIM:617106; Episodic ataxia, type 2, OMIM:108500; Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia, OMIM:141500
Adult onset neurodegenerative disorder v2.223 CACNA1A Arina Puzriakova Added comment: Comment on mode of inheritance: CACNA1A is associated with several phenotypes including SCA6 (OMIM:183086), episodic ataxia (OMIM:108500), familial hemiplegic migraine with or without ataxia (OMIM:141500), or developmental and epileptic encephalopathy (OMIM:617106). SCA6 is the only condition that may align with this panel; however, it is caused by nucleotide repeat expansions and there is a lack of relevance for SNVs.
Adult onset neurodegenerative disorder v2.223 CACNA1A Arina Puzriakova Mode of inheritance for gene: CACNA1A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to Other
Congenital myaesthenic syndrome v2.39 CACNA1A Arina Puzriakova Phenotypes for gene: CACNA1A were changed from episodic ataxia plus myasthenic syndrome; hemiplegic migraine plus disturbed NMJ function to Lambert-Eaton myasthenic syndrome, MONDO:0018556
Adult onset neurodegenerative disorder v2.222 CACNA1A Arina Puzriakova Tag treatable was removed from gene: CACNA1A.
Tag currently-ngs-unreportable tag was added to gene: CACNA1A.
Adult onset neurodegenerative disorder v2.222 CACNA1A Arina Puzriakova Phenotypes for gene: CACNA1A were changed from episodic ataxia type 2 (EA2),108500; familial hemiplegic migraine type 1, 141500; Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia; Dystonia; Spinocerebellar ataxia 6; Episodic ataxia, type 2 to Spinocerebellar ataxia 6, OMIM:183086
Paroxysmal central nervous system disorders v1.22 CACNA1A Arina Puzriakova Phenotypes for gene: CACNA1A were changed from Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia, 141500; EA2; Migraine, familial hemiplegic, 1, 141500; Episodic Ataxia, Type 2; familial hemiplegic migraine type 1, 141500; episodic ataxia type 2 (EA2),108500; Spinocerebellar ataxia 6, 183086; Episodic ataxia, type 2, 108500 to Episodic ataxia, type 2, OMIM:108500; Migraine, familial hemiplegic, 1, OMIM:141500; Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia, OMIM:141500
Albinism or congenital nystagmus v1.20 CACNA1A Arina Puzriakova Phenotypes for gene: CACNA1A were changed from CACNA1A-Related Episodic Ataxia Type 2; Acetazolamide-Responsive Hereditary Paroxysmal Cerebellar Ataxia; Episodic Ataxia Type 2 (EA2) Episodic Ataxia, Nystagmus-Associated to Episodic ataxia, type 2, OMIM:108500
Hereditary ataxia v1.262 CACNA1A Arina Puzriakova Tag nucleotide-repeat-expansion was removed from gene: CACNA1A.
Adult onset dystonia, chorea or related movement disorder v1.139 CACNA1A Arina Puzriakova Phenotypes for gene: CACNA1A were changed from Episodic ataxia, type 2, OMIM:108500; Spinocerebellar ataxia 6, OMIM:183086; Migraine, familial hemiplegic, 1, OMIM:141500; Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia, OMIM:141500 to Episodic ataxia, type 2, OMIM:108500; Migraine, familial hemiplegic, 1, OMIM:141500; Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia, OMIM:141500
Hereditary ataxia with onset in adulthood v2.107 CACNA1A Arina Puzriakova Phenotypes for gene: CACNA1A were changed from SCA6, 183086; familial hemiplegic migraine type 1, 141500; Episodic ataxia, type 2; Spinocerebellar ataxia 6; Familial hemiplegic migraine 1, 141500; Episodic ataxia type 2, 108500; Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia; episodic ataxia type 2 (EA2),108500 to Episodic ataxia, type 2, OMIM:108500; Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia, OMIM:141500
Hereditary ataxia v1.262 CACNA1A Arina Puzriakova Phenotypes for gene: CACNA1A were changed from Episodic ataxia, type 2; Spinocerebellar ataxia 6; Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia to Episodic ataxia, type 2, OMIM:108500; Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia, OMIM:141500
Ataxia and cerebellar anomalies - narrow panel v2.260 CACNA1A Arina Puzriakova Phenotypes for gene: CACNA1A were changed from Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia; Spinocerebellar ataxia 6; Episodic ataxia, type 2 to Episodic ataxia, type 2, OMIM:108500; Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia, OMIM:141500
Skeletal muscle channelopathy v1.32 CACNA1A Arina Puzriakova Phenotypes for gene: CACNA1A were changed from Episodic ataxia 2 with periodic paralysis; Epileptic encephalopathy, early infantile, 42 OMIM:617106; Migraine, familial hemiplegic, 1 OMIM:141500; Episodic ataxia, type 2 OMIM:108500 to Episodic ataxia, type 2, OMIM:108500; Migraine, familial hemiplegic, 1, OMIM:141500; Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia, OMIM:141500
Childhood onset dystonia, chorea or related movement disorder v1.181 CACNA1A Arina Puzriakova Phenotypes for gene: CACNA1A were changed from familial hemiplegic migraine type 1, 141500; Dystonia; episodic ataxia type 2 (EA2), 108500 to Episodic ataxia, type 2, OMIM:108500
Early onset dystonia v1.94 CACNA1A Arina Puzriakova Phenotypes for gene: CACNA1A were changed from Dystonia to Episodic ataxia, type 2, OMIM:108500
Early onset dystonia v1.93 CACNA1A Arina Puzriakova Mode of inheritance for gene: CACNA1A was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brain channelopathy v1.65 CACNA1A Arina Puzriakova Phenotypes for gene: CACNA1A were changed from episodic ataxia type 2 (EA2),108500; familial hemiplegic migraine type 1, 141500 to Episodic ataxia, type 2, OMIM:108500; Migraine, familial hemiplegic, 1, OMIM:141500; Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia, OMIM:141500
Skeletal Muscle Channelopathies v1.38 CACNA1A Arina Puzriakova Phenotypes for gene: CACNA1A were changed from Migraine, familial hemiplegic, 1, 141500; Episodic ataxia, type 2, 108500; Spinocerebellar ataxia 6, 183086; Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia, 141500; Episodic Ataxia, Type 2; EA2 to Episodic ataxia, type 2, OMIM:108500; Migraine, familial hemiplegic, 1, OMIM:141500; Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia, OMIM:141500
Familial Meniere Disease v1.2 CACNA1A Arina Puzriakova Phenotypes for gene: CACNA1A were changed from Episodic ataxia type 2; migraine familial hemiplegic type 1 to Episodic ataxia, type 2, OMIM:108500; Migraine, familial hemiplegic, 1, OMIM:141500; Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia, OMIM:141500
Infantile nystagmus v1.4 CACNA1A Arina Puzriakova Phenotypes for gene: CACNA1A were changed from CACNA1A-Related Episodic Ataxia Type 2; Episodic Ataxia Type 2 (EA2) Episodic Ataxia, Nystagmus-Associated; Acetazolamide-Responsive Hereditary Paroxysmal Cerebellar Ataxia to Episodic ataxia, type 2, OMIM:108500
Adult onset dystonia, chorea or related movement disorder v1.138 CACNA1A_CAG Arina Puzriakova Phenotypes for STR: CACNA1A_CAG were changed from Spinocerebellar ataxia 6 183086 to Spinocerebellar ataxia 6, OMIM:183086
Adult onset dystonia, chorea or related movement disorder v1.137 CACNA1A_CAG Arina Puzriakova Tag watchlist tag was added to STR: CACNA1A_CAG.
Hereditary ataxia with onset in adulthood v2.106 CACNA1A_CAG Arina Puzriakova Phenotypes for STR: CACNA1A_CAG were changed from Spinocerebellar ataxia 6 183086 to Spinocerebellar ataxia 6, OMIM:183086
Adult onset neurodegenerative disorder v2.221 CACNA1A_CAG Arina Puzriakova Phenotypes for STR: CACNA1A_CAG were changed from Spinocerebellar ataxia 6 183086 to Spinocerebellar ataxia 6, OMIM:183086
Adult onset neurodegenerative disorder v2.220 CACNA1A_CAG Arina Puzriakova Tag watchlist tag was added to STR: CACNA1A_CAG.
Adult onset hereditary spastic paraplegia v1.78 CACNA1A_CAG Arina Puzriakova Phenotypes for STR: CACNA1A_CAG were changed from Spinocerebellar ataxia 6 183086 to Spinocerebellar ataxia 6, OMIM:183086
Childhood onset hereditary spastic paraplegia v2.92 CACNA1A_CAG Arina Puzriakova Phenotypes for STR: CACNA1A_CAG were changed from Spinocerebellar ataxia 6 183086 to Spinocerebellar ataxia 6, OMIM:183086
Hereditary spastic paraplegia v1.264 CACNA1A_CAG Arina Puzriakova Phenotypes for STR: CACNA1A_CAG were changed from Spinocerebellar ataxia 6 183086 to Spinocerebellar ataxia 6, OMIM:183086
Paroxysmal central nervous system disorders v1.21 CACNA1A_CAG Arina Puzriakova Phenotypes for STR: CACNA1A_CAG were changed from Spinocerebellar ataxia 6 183086 to Spinocerebellar ataxia 6, OMIM:183086
Hereditary ataxia v1.261 CACNA1A_CAG Arina Puzriakova Phenotypes for STR: CACNA1A_CAG were changed from Spinocerebellar ataxia 6 183086 to Spinocerebellar ataxia 6, OMIM:183086
Ataxia and cerebellar anomalies - narrow panel v2.259 CACNA1A_CAG Arina Puzriakova Phenotypes for STR: CACNA1A_CAG were changed from Spinocerebellar ataxia 6 183086 to Spinocerebellar ataxia 6, OMIM:183086
Ataxia and cerebellar anomalies - narrow panel v2.258 CACNA1A_CAG Arina Puzriakova Tag watchlist tag was added to STR: CACNA1A_CAG.
Brain channelopathy v1.64 CACNA1A_CAG Arina Puzriakova Phenotypes for STR: CACNA1A_CAG were changed from Spinocerebellar ataxia 6 183086 to Spinocerebellar ataxia 6, OMIM:183086
Adult onset dystonia, chorea or related movement disorder v1.137 C9orf72_GGGGCC Arina Puzriakova Phenotypes for STR: C9orf72_GGGGCC were changed from Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 OMIM:105550; frontotemporal dementia and/or amyotrophic lateral sclerosis 1 MONDO:0007105 to Frontotemporal dementia and/or amyotrophic lateral sclerosis 1, OMIM:105550
Intellectual disability v3.1426 C9orf72_GGGGCC Arina Puzriakova Phenotypes for STR: C9orf72_GGGGCC were changed from Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 105550 to Frontotemporal dementia and/or amyotrophic lateral sclerosis 1, OMIM:105550
Amyotrophic lateral sclerosis/motor neuron disease v1.46 C9orf72_GGGGCC Arina Puzriakova Phenotypes for STR: C9orf72_GGGGCC were changed from Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 105550 to Frontotemporal dementia and/or amyotrophic lateral sclerosis 1, OMIM:105550
Adult onset neurodegenerative disorder v2.220 C9orf72_GGGGCC Arina Puzriakova Phenotypes for STR: C9orf72_GGGGCC were changed from Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 105550 to Frontotemporal dementia and/or amyotrophic lateral sclerosis 1, OMIM:105550
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.57 C9orf72_GGGGCC Arina Puzriakova Phenotypes for STR: C9orf72_GGGGCC were changed from Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 105550 to Frontotemporal dementia and/or amyotrophic lateral sclerosis 1, OMIM:105550
Parkinson Disease and Complex Parkinsonism v1.81 C9orf72_GGGGCC Arina Puzriakova Phenotypes for STR: C9orf72_GGGGCC were changed from Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 105550 to Frontotemporal dementia and/or amyotrophic lateral sclerosis 1, OMIM:105550
Childhood onset dystonia, chorea or related movement disorder v1.180 C9orf72_GGGGCC Arina Puzriakova Phenotypes for STR: C9orf72_GGGGCC were changed from Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 OMIM:105550; frontotemporal dementia and/or amyotrophic lateral sclerosis 1 MONDO:0007105 to Frontotemporal dementia and/or amyotrophic lateral sclerosis 1, OMIM:105550
Parkinson Disease and Complex Parkinsonism v1.80 C9orf72 Arina Puzriakova Phenotypes for gene: C9orf72 were changed from (Hexanucleotideexpansion); clinical presentation suggestive of cortico-basal/PSP syndrome; complex parkinsonism to Frontotemporal dementia and/or amyotrophic lateral sclerosis 1, OMIM:105550
Parkinson Disease and Complex Parkinsonism v1.79 C9orf72 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Parkinson Disease and Complex Parkinsonism v1.79 C9orf72 Arina Puzriakova Mode of inheritance for gene: C9orf72 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Other
Parkinson Disease and Complex Parkinsonism v1.78 C9orf72 Arina Puzriakova Tag currently-ngs-unreportable tag was added to gene: C9orf72.
Intellectual disability v3.1425 C9orf72 Arina Puzriakova Mode of pathogenicity for gene: C9orf72 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
Adult onset dystonia, chorea or related movement disorder v1.136 C9orf72 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Adult onset dystonia, chorea or related movement disorder v1.136 C9orf72 Arina Puzriakova Mode of inheritance for gene: C9orf72 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Other
Intellectual disability v3.1424 C9orf72 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Intellectual disability v3.1424 C9orf72 Arina Puzriakova Mode of inheritance for gene: C9orf72 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Other
Amyotrophic lateral sclerosis/motor neuron disease v1.45 C9orf72 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Amyotrophic lateral sclerosis/motor neuron disease v1.45 C9orf72 Arina Puzriakova Mode of inheritance for gene: C9orf72 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to Other
Adult onset neurodegenerative disorder v2.219 C9orf72 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Adult onset neurodegenerative disorder v2.219 C9orf72 Arina Puzriakova Mode of inheritance for gene: C9orf72 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Other
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.56 C9orf72 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.56 C9orf72 Arina Puzriakova Mode of inheritance for gene: C9orf72 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Other
Childhood onset dystonia, chorea or related movement disorder v1.179 C9orf72 Arina Puzriakova commented on gene: C9orf72
Childhood onset dystonia, chorea or related movement disorder v1.179 C9orf72 Arina Puzriakova Tag Q4_21_MOI tag was added to gene: C9orf72.
Childhood onset dystonia, chorea or related movement disorder v1.179 C9orf72 Arina Puzriakova Tag Q2_21_phenotype was removed from gene: C9orf72.
Tag Q2_21_expert_review was removed from gene: C9orf72.
Tag Q4_21_rating tag was added to gene: C9orf72.
Childhood onset dystonia, chorea or related movement disorder v1.179 C9orf72 Arina Puzriakova Phenotypes for gene: C9orf72 were changed from Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 OMIM:105550; frontotemporal dementia and/or amyotrophic lateral sclerosis 1 MONDO:0007105 to Frontotemporal dementia and/or amyotrophic lateral sclerosis 1, OMIM:105550
Adult onset dystonia, chorea or related movement disorder v1.135 C9orf72 Arina Puzriakova Phenotypes for gene: C9orf72 were changed from complex parkinsonism; (Hexanucleotideexpansion); clinical presentation suggestive of cortico-basal/PSP syndrome to Frontotemporal dementia and/or amyotrophic lateral sclerosis 1, OMIM:105550
Intellectual disability v3.1423 C9orf72 Arina Puzriakova Phenotypes for gene: C9orf72 were changed from Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 105550 to Frontotemporal dementia and/or amyotrophic lateral sclerosis 1, OMIM:105550
Adult onset dystonia, chorea or related movement disorder v1.134 C9orf72 Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: C9orf72.
Tag currently-ngs-unreportable tag was added to gene: C9orf72.
Amyotrophic lateral sclerosis/motor neuron disease v1.44 C9orf72 Arina Puzriakova Publications for gene: C9orf72 were set to PMID: 21944778; 21944779; 25638642; 27059391; 23597494
Amyotrophic lateral sclerosis/motor neuron disease v1.43 C9orf72 Arina Puzriakova Phenotypes for gene: C9orf72 were changed from Amyotrophic Lateral Sclerosis/Frontotemporal Dementia; Amyotrophic lateral sclerosis and/or frontotemporal dementia, 105550 -3; Hexanucleotide repeat expansion; Frontotemporal Dementia, Amyotrophic Lateral Sclerosis; amyotrophic lateral sclerosis; frontotemporal dementia; Frontotemporal Dementia, Amyotrophic Lateral Sclerosis to Frontotemporal dementia and/or amyotrophic lateral sclerosis 1, OMIM:105550
Amyotrophic lateral sclerosis/motor neuron disease v1.42 C9orf72 Arina Puzriakova Tag currently-ngs-unreportable tag was added to gene: C9orf72.
Adult onset neurodegenerative disorder v2.218 C9orf72 Arina Puzriakova Phenotypes for gene: C9orf72 were changed from complex parkinsonism; Amyotrophic Lateral Sclerosis/Frontotemporal Dementia; Amyotrophic lateral sclerosis and/or frontotemporal dementia, 105550 -3; clinical presentation suggestive of cortico-basal/PSP syndrome; (Hexanucleotideexpansion); Frontotemporal Dementia And/Or Amyotrophic Lateral Sclerosis; Clinical syndrome FTLD (Frontotemporal lobar degeneration); Frontotemporal Dementia, Amyotrophic Lateral Sclerosis; Hexanucleotide repeat expansion; amyotrophic lateral sclerosis; frontotemporal dementia to Frontotemporal dementia and/or amyotrophic lateral sclerosis 1, OMIM:105550
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.55 C9orf72 Arina Puzriakova Phenotypes for gene: C9orf72 were changed from Amyotrophic lateral sclerosis and/or frontotemporal dementia, 105550 -3; Amyotrophic Lateral Sclerosis/Frontotemporal Dementia; Frontotemporal Dementia And/Or Amyotrophic Lateral Sclerosis; Clinical syndrome FTLD (Frontotemporal lobar degeneration) to Frontotemporal dementia and/or amyotrophic lateral sclerosis 1, OMIM:105550
Fetal anomalies v1.796 MMP15 Ivone Leong Tag watchlist tag was added to gene: MMP15.
Fetal anomalies v1.796 MMP15 Ivone Leong Classified gene: MMP15 as Amber List (moderate evidence)
Fetal anomalies v1.796 MMP15 Ivone Leong Added comment: Comment on list classification: New gene added by Dmitrijs Rots (RadboudUMC). This gene is not associated with a phenotype in OMIM or Gene2Phenotype.

PMID: 33875846 describes 3 patients from 2 families with biallelic variants in MMP15 (one is Pro353fs and other is Gly231Arg). One family with 2 affected siblings presented with cholestasis, hepatomegaly, high hepatic transaminases, and congenital heart disease. The other unrelated case showed similar symptoms.

As there are only 2 cases and currently there are no animal models that replicate the human phenotype this gene has been given an Amber rating until more evidence is available.
Fetal anomalies v1.796 MMP15 Ivone Leong Gene: mmp15 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.795 MMP15 Ivone Leong Phenotypes for gene: MMP15 were changed from Cholestasis; congenital heart disease to Cholestasis, MONDO:0001751; congenital heart disease, MONDO:0005453
Fetal anomalies v1.794 MMP15 Ivone Leong Publications for gene: MMP15 were set to PMID: 33875846
Cholestasis v1.91 MMP15 Ivone Leong Tag watchlist tag was added to gene: MMP15.
Cholestasis v1.91 MMP15 Ivone Leong Classified gene: MMP15 as Amber List (moderate evidence)
Cholestasis v1.91 MMP15 Ivone Leong Added comment: Comment on list classification: New gene added by Dmitrijs Rots (RadboudUMC). This gene is not associated with a phenotype in OMIM or Gene2Phenotype.

PMID: 33875846 describes 3 patients from 2 families with biallelic variants in MMP15 (one is Pro353fs and other is Gly231Arg). One family with 2 affected siblings presented with cholestasis, hepatomegaly, high hepatic transaminases, and congenital heart disease. The other unrelated case showed similar symptoms.

As there are only 2 cases and currently there are no animal models that replicate the human phenotype this gene has been given an Amber rating until more evidence is available.
Cholestasis v1.91 MMP15 Ivone Leong Gene: mmp15 has been classified as Amber List (Moderate Evidence).
Cholestasis v1.90 MMP15 Ivone Leong Phenotypes for gene: MMP15 were changed from Cholestasis; congenital heart disease to Cholestasis, MONDO:0001751; congenital heart disease, MONDO:0005453
Cholestasis v1.89 MMP15 Ivone Leong Publications for gene: MMP15 were set to PMID: 33875846
Retinal disorders v2.233 ATXN7 Arina Puzriakova Mode of pathogenicity for gene: ATXN7 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
Retinal disorders v2.232 ATXN7 Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: ATXN7.
Tag currently-ngs-unreportable tag was added to gene: ATXN7.
Intellectual disability v3.1422 ATXN7_CAG Arina Puzriakova Phenotypes for STR: ATXN7_CAG were changed from Spinocerebellar ataxia 7 164500 to Spinocerebellar ataxia 7, OMIM:164500
Hereditary ataxia with onset in adulthood v2.105 ATXN7_CAG Arina Puzriakova Phenotypes for STR: ATXN7_CAG were changed from Spinocerebellar ataxia 7 164500 to Spinocerebellar ataxia 7, OMIM:164500
Hereditary neuropathy v1.422 ATXN7_CAG Arina Puzriakova Phenotypes for STR: ATXN7_CAG were changed from Spinocerebellar ataxia 7 164500; Adult onset, cerebellar ataxia, pigmentary macular degeneration, sensory-motor axonal neuropathy to Spinocerebellar ataxia 7, OMIM:164500
Undiagnosed metabolic disorders v1.491 ATXN7_CAG Arina Puzriakova Phenotypes for STR: ATXN7_CAG were changed from Spinocerebellar ataxia 7 164500 to Spinocerebellar ataxia 7, OMIM:164500
Adult onset neurodegenerative disorder v2.217 ATXN7_CAG Arina Puzriakova Phenotypes for STR: ATXN7_CAG were changed from Spinocerebellar ataxia 7 164500 to Spinocerebellar ataxia 7, OMIM:164500
Adult onset neurodegenerative disorder v2.216 ATXN7_CAG Arina Puzriakova Tag watchlist tag was added to STR: ATXN7_CAG.
Adult onset hereditary spastic paraplegia v1.77 ATXN7_CAG Arina Puzriakova Phenotypes for STR: ATXN7_CAG were changed from Spinocerebellar ataxia 7 164500 to Spinocerebellar ataxia 7, OMIM:164500
Childhood onset hereditary spastic paraplegia v2.91 ATXN7_CAG Arina Puzriakova Phenotypes for STR: ATXN7_CAG were changed from Spinocerebellar ataxia 7 164500 to Spinocerebellar ataxia 7, OMIM:164500
Hereditary spastic paraplegia v1.263 ATXN7_CAG Arina Puzriakova Phenotypes for STR: ATXN7_CAG were changed from Spinocerebellar ataxia 7 164500 to Spinocerebellar ataxia 7, OMIM:164500
Hereditary ataxia v1.260 ATXN7_CAG Arina Puzriakova Phenotypes for STR: ATXN7_CAG were changed from Spinocerebellar ataxia 7 164500 to Spinocerebellar ataxia 7, OMIM:164500
Ataxia and cerebellar anomalies - narrow panel v2.258 ATXN7_CAG Arina Puzriakova Phenotypes for STR: ATXN7_CAG were changed from Spinocerebellar ataxia 7 164500 to Spinocerebellar ataxia 7, OMIM:164500
Retinal disorders v2.232 ATXN7 Arina Puzriakova Classified gene: ATXN7 as Red List (low evidence)
Retinal disorders v2.232 ATXN7 Arina Puzriakova Gene: atxn7 has been classified as Red List (Low Evidence).
Retinal disorders v2.231 ATXN7 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Retinal disorders v2.231 ATXN7 Arina Puzriakova Mode of inheritance for gene: ATXN7 was changed from to Other
Retinal disorders v2.230 ATXN7 Arina Puzriakova Phenotypes for gene: ATXN7 were changed from to Spinocerebellar ataxia 7, OMIM:164500
Intellectual disability v3.1421 ATXN7 Arina Puzriakova Phenotypes for gene: ATXN7 were changed from Spinocerebellar ataxia 7 164500 to Spinocerebellar ataxia 7, OMIM:164500
Likely inborn error of metabolism v2.192 ATXN7 Arina Puzriakova Phenotypes for gene: ATXN7 were changed from Spinocerebellar ataxia 7 164500; Spinocerebellar ataxia-7 (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) to Spinocerebellar ataxia 7, OMIM:164500; Mitochondrial respiratory chain disorders (caused by nuclear variants only)
Childhood onset dystonia, chorea or related movement disorder v1.178 ATXN7 Arina Puzriakova Phenotypes for gene: ATXN7 were changed from Spinocerebellar ataxia 7, 164500 to Spinocerebellar ataxia 7, OMIM:164500
Hereditary ataxia with onset in adulthood v2.104 ATXN7 Arina Puzriakova Phenotypes for gene: ATXN7 were changed from Spinocerebellarataxia 7,164500; Spinocerebellar ataxia 7, 164500 to Spinocerebellar ataxia 7, OMIM:164500
Undiagnosed metabolic disorders v1.490 ATXN7 Arina Puzriakova Phenotypes for gene: ATXN7 were changed from Spinocerebellar ataxia-7 (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Spinocerebellar ataxia 7 164500 to Spinocerebellar ataxia 7, OMIM:164500
Adult onset neurodegenerative disorder v2.216 ATXN7 Arina Puzriakova Phenotypes for gene: ATXN7 were changed from Spinocerebellarataxia7,164500 to Spinocerebellar ataxia 7, OMIM:164500
Hereditary ataxia v1.259 ATXN7 Arina Puzriakova Phenotypes for gene: ATXN7 were changed from Spinocerebellarataxia7,164500 to Spinocerebellar ataxia 7, OMIM:164500
Ataxia and cerebellar anomalies - narrow panel v2.257 ATXN7 Arina Puzriakova Phenotypes for gene: ATXN7 were changed from Spinocerebellarataxia7,164500 to Spinocerebellar ataxia 7, OMIM:164500
Childhood onset dystonia, chorea or related movement disorder v1.177 ATXN1 Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: ATXN1.
Tag currently-ngs-unreportable tag was added to gene: ATXN1.
Childhood onset dystonia, chorea or related movement disorder v1.177 ATXN1 Arina Puzriakova Classified gene: ATXN1 as Red List (low evidence)
Childhood onset dystonia, chorea or related movement disorder v1.177 ATXN1 Arina Puzriakova Gene: atxn1 has been classified as Red List (Low Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.176 ATXN1 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Childhood onset dystonia, chorea or related movement disorder v1.176 ATXN1 Arina Puzriakova Mode of inheritance for gene: ATXN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Other
Childhood onset dystonia, chorea or related movement disorder v1.175 ATXN7 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Childhood onset dystonia, chorea or related movement disorder v1.175 ATXN7 Arina Puzriakova Mode of inheritance for gene: ATXN7 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Other
Childhood onset dystonia, chorea or related movement disorder v1.174 ATXN7 Arina Puzriakova Classified gene: ATXN7 as Red List (low evidence)
Childhood onset dystonia, chorea or related movement disorder v1.174 ATXN7 Arina Puzriakova Gene: atxn7 has been classified as Red List (Low Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.173 ATXN7 Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: ATXN7.
Tag currently-ngs-unreportable tag was added to gene: ATXN7.
Intellectual disability v3.1420 ATXN7 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Intellectual disability v3.1420 ATXN7 Arina Puzriakova Mode of inheritance for gene: ATXN7 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Other
Likely inborn error of metabolism v2.191 ATXN7 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Likely inborn error of metabolism v2.191 ATXN7 Arina Puzriakova Mode of inheritance for gene: ATXN7 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to Other
Hereditary ataxia with onset in adulthood v2.103 ATXN7 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Hereditary ataxia with onset in adulthood v2.103 ATXN7 Arina Puzriakova Mode of inheritance for gene: ATXN7 was changed from Unknown to Other
Likely inborn error of metabolism v2.190 ATXN7 Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: ATXN7.
Tag currently-ngs-unreportable tag was added to gene: ATXN7.
Undiagnosed metabolic disorders v1.489 ATXN7 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Undiagnosed metabolic disorders v1.489 ATXN7 Arina Puzriakova Mode of inheritance for gene: ATXN7 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to Other
Adult onset neurodegenerative disorder v2.215 ATXN7 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Adult onset neurodegenerative disorder v2.215 ATXN7 Arina Puzriakova Mode of inheritance for gene: ATXN7 was changed from Unknown to Other
Hereditary ataxia v1.258 ATXN7 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Hereditary ataxia v1.258 ATXN7 Arina Puzriakova Mode of inheritance for gene: ATXN7 was changed from to Other
Ataxia and cerebellar anomalies - narrow panel v2.256 ATXN7 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Ataxia and cerebellar anomalies - narrow panel v2.256 ATXN7 Arina Puzriakova Mode of inheritance for gene: ATXN7 was changed from Unknown to Other
Ataxia and cerebellar anomalies - narrow panel v2.255 ATXN7 Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: ATXN7.
Tag currently-ngs-unreportable tag was added to gene: ATXN7.
Adult onset dystonia, chorea or related movement disorder v1.134 ATXN3_CAG Arina Puzriakova Phenotypes for STR: ATXN3_CAG were changed from Machado-Joseph disease 109150 to Machado-Joseph disease, OMIM:109150
Adult onset dystonia, chorea or related movement disorder v1.133 ATXN3_CAG Arina Puzriakova Tag watchlist tag was added to STR: ATXN3_CAG.
Hereditary ataxia with onset in adulthood v2.102 ATXN3_CAG Arina Puzriakova Phenotypes for STR: ATXN3_CAG were changed from Machado-Joseph disease 109150 to Machado-Joseph disease, OMIM:109150
Hereditary neuropathy v1.421 ATXN3_CAG Arina Puzriakova Phenotypes for STR: ATXN3_CAG were changed from Machado-Joseph disease 109150 to Machado-Joseph disease, OMIM:109150
Intellectual disability v3.1419 ATXN3_CAG Arina Puzriakova Phenotypes for STR: ATXN3_CAG were changed from Machado-Joseph disease 109150 to Machado-Joseph disease, OMIM:109150
Adult onset neurodegenerative disorder v2.214 ATXN3_CAG Arina Puzriakova Phenotypes for STR: ATXN3_CAG were changed from Machado-Joseph disease 109150 to Machado-Joseph disease, OMIM:109150
Adult onset neurodegenerative disorder v2.213 ATXN3_CAG Arina Puzriakova Tag watchlist tag was added to STR: ATXN3_CAG.
Adult onset hereditary spastic paraplegia v1.76 ATXN3_CAG Arina Puzriakova Phenotypes for STR: ATXN3_CAG were changed from Machado-Joseph disease 109150 to Machado-Joseph disease, OMIM:109150
Childhood onset hereditary spastic paraplegia v2.90 ATXN3_CAG Arina Puzriakova Phenotypes for STR: ATXN3_CAG were changed from Machado-Joseph disease 109150 to Machado-Joseph disease, OMIM:109150
Hereditary spastic paraplegia v1.262 ATXN3_CAG Arina Puzriakova Phenotypes for STR: ATXN3_CAG were changed from Machado-Joseph disease 109150 to Machado-Joseph disease, OMIM:109150
Hereditary ataxia v1.257 ATXN3_CAG Arina Puzriakova Phenotypes for STR: ATXN3_CAG were changed from Machado-Joseph disease 109150 to Machado-Joseph disease, OMIM:109150
Ataxia and cerebellar anomalies - narrow panel v2.255 ATXN3_CAG Arina Puzriakova Phenotypes for STR: ATXN3_CAG were changed from Machado-Joseph disease 109150 to Machado-Joseph disease, OMIM:109150
Ataxia and cerebellar anomalies - narrow panel v2.254 ATXN3_CAG Arina Puzriakova Tag watchlist tag was added to STR: ATXN3_CAG.
Early onset dystonia v1.92 ATXN3_CAG Arina Puzriakova Phenotypes for STR: ATXN3_CAG were changed from Machado-Joseph disease 109150 to Machado-Joseph disease, OMIM:109150
Parkinson Disease and Complex Parkinsonism v1.78 ATXN3_CAG Arina Puzriakova Phenotypes for STR: ATXN3_CAG were changed from Machado-Joseph disease 109150 to Machado-Joseph disease, OMIM:109150
Intellectual disability v3.1418 ATXN3 Arina Puzriakova Mode of pathogenicity for gene: ATXN3 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
Adult onset dystonia, chorea or related movement disorder v1.133 ATXN3 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Adult onset dystonia, chorea or related movement disorder v1.133 ATXN3 Arina Puzriakova Mode of inheritance for gene: ATXN3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Other
Hereditary ataxia with onset in adulthood v2.101 ATXN3 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Hereditary ataxia with onset in adulthood v2.101 ATXN3 Arina Puzriakova Mode of inheritance for gene: ATXN3 was changed from Unknown to Other
Adult onset neurodegenerative disorder v2.213 ATXN3 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Adult onset neurodegenerative disorder v2.213 ATXN3 Arina Puzriakova Mode of inheritance for gene: ATXN3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Other
Hereditary ataxia v1.256 ATXN3 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Hereditary ataxia v1.256 ATXN3 Arina Puzriakova Mode of inheritance for gene: ATXN3 was changed from to Other
Intellectual disability v3.1417 ATXN3 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Intellectual disability v3.1417 ATXN3 Arina Puzriakova Mode of inheritance for gene: ATXN3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Other
Ataxia and cerebellar anomalies - narrow panel v2.254 ATXN3 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Ataxia and cerebellar anomalies - narrow panel v2.254 ATXN3 Arina Puzriakova Mode of inheritance for gene: ATXN3 was changed from Unknown to Other
Parkinson Disease and Complex Parkinsonism v1.77 ATXN3 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Parkinson Disease and Complex Parkinsonism v1.77 ATXN3 Arina Puzriakova Mode of inheritance for gene: ATXN3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Other
Intellectual disability v3.1416 ATXN3 Arina Puzriakova Phenotypes for gene: ATXN3 were changed from Machado-Joseph disease 109150 to Machado-Joseph disease, OMIM:109150
Adult onset dystonia, chorea or related movement disorder v1.132 ATXN3 Arina Puzriakova Phenotypes for gene: ATXN3 were changed from (CAGexpansion); familial parkinsonism to Machado-Joseph disease, OMIM:109150
Adult onset dystonia, chorea or related movement disorder v1.131 ATXN3 Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: ATXN3.
Tag currently-ngs-unreportable tag was added to gene: ATXN3.
Hereditary ataxia with onset in adulthood v2.100 ATXN3 Arina Puzriakova Phenotypes for gene: ATXN3 were changed from Machado-Joseph disease, 109150 to Machado-Joseph disease, OMIM:109150
Intellectual disability v3.1415 ATXN3 Arina Puzriakova Tag currently-ngs-unreportable tag was added to gene: ATXN3.
Adult onset neurodegenerative disorder v2.212 ATXN3 Arina Puzriakova Phenotypes for gene: ATXN3 were changed from familial parkinsonism; (CAGexpansion) to Machado-Joseph disease, OMIM:109150; Susceptibility to Late-Onset Parkinson Disease
Hereditary ataxia v1.255 ATXN3 Arina Puzriakova Phenotypes for gene: ATXN3 were changed from to Machado-Joseph disease, OMIM:109150
Ataxia and cerebellar anomalies - narrow panel v2.253 ATXN3 Arina Puzriakova Phenotypes for gene: ATXN3 were changed from to Machado-Joseph disease, OMIM:109150
Ataxia and cerebellar anomalies - narrow panel v2.252 ATXN3 Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: ATXN3.
Tag currently-ngs-unreportable tag was added to gene: ATXN3.
Parkinson Disease and Complex Parkinsonism v1.76 ATXN3 Arina Puzriakova Phenotypes for gene: ATXN3 were changed from (CAGexpansion); familial parkinsonism to Machado-Joseph disease, OMIM:109150; Susceptibility to Late-Onset Parkinson Disease
Xeroderma pigmentosum, Trichothiodystrophy or Cockayne syndrome v2.18 TARS Alan Lehmann reviewed gene: TARS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Trichothiodystrophy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Xeroderma pigmentosum, Trichothiodystrophy or Cockayne syndrome v2.18 CARS Alan Lehmann reviewed gene: CARS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Trichothiodystrophy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.1415 ATXN2_CAG Arina Puzriakova Phenotypes for STR: ATXN2_CAG were changed from Spinocerebellar ataxia 2 183090 to Spinocerebellar ataxia 2, OMIM:183090; {Amyotrophic lateral sclerosis, susceptibility to, 13}, OMIM:183090; {Parkinson disease, late-onset, susceptibility to}, OMIM:168600
Xeroderma pigmentosum, Trichothiodystrophy or Cockayne syndrome v2.18 MARS Alan Lehmann reviewed gene: MARS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Trichothiodystrophy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary spastic paraplegia v1.261 ATXN2_CAG Arina Puzriakova Phenotypes for STR: ATXN2_CAG were changed from Spinocerebellar ataxia 2 183090 to Spinocerebellar ataxia 2, OMIM:183090; {Amyotrophic lateral sclerosis, susceptibility to, 13}, OMIM:183090
Xeroderma pigmentosum, Trichothiodystrophy or Cockayne syndrome v2.18 AARS Alan Lehmann reviewed gene: AARS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Trichothiodystrophy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.420 ATXN2_CAG Arina Puzriakova Phenotypes for STR: ATXN2_CAG were changed from Spinocerebellar ataxia 2 183090 to Spinocerebellar ataxia 2, OMIM:183090; {Amyotrophic lateral sclerosis, susceptibility to, 13}, OMIM:183090
Adult onset hereditary spastic paraplegia v1.75 ATXN2_CAG Arina Puzriakova Phenotypes for STR: ATXN2_CAG were changed from Spinocerebellar ataxia 2 183090 to Spinocerebellar ataxia 2, OMIM:183090; {Amyotrophic lateral sclerosis, susceptibility to, 13}, OMIM:183090
Childhood onset hereditary spastic paraplegia v2.89 ATXN2_CAG Arina Puzriakova Phenotypes for STR: ATXN2_CAG were changed from Spinocerebellar ataxia 2 183090 to Spinocerebellar ataxia 2, OMIM:183090; {Amyotrophic lateral sclerosis, susceptibility to, 13}, OMIM:183090
Ataxia and cerebellar anomalies - narrow panel v2.252 ATXN2_CAG Arina Puzriakova Phenotypes for STR: ATXN2_CAG were changed from Spinocerebellar ataxia 2 183090 to Spinocerebellar ataxia 2, OMIM:183090
Amyotrophic lateral sclerosis/motor neuron disease v1.42 ATXN2_CAG Arina Puzriakova Phenotypes for STR: ATXN2_CAG were changed from Spinocerebellar ataxia 2 183090 to {Amyotrophic lateral sclerosis, susceptibility to, 13}, OMIM:183090
Adult onset neurodegenerative disorder v2.211 ATXN2_CAG Arina Puzriakova Phenotypes for STR: ATXN2_CAG were changed from Spinocerebellar ataxia 2 183090 to Spinocerebellar ataxia 2, OMIM:183090; {Amyotrophic lateral sclerosis, susceptibility to, 13}, OMIM:183090; {Parkinson disease, late-onset, susceptibility to}, OMIM:168600
Adult onset neurodegenerative disorder v2.210 ATXN2_CAG Arina Puzriakova Tag watchlist tag was added to STR: ATXN2_CAG.
Hereditary ataxia v1.254 ATXN2_CAG Arina Puzriakova Phenotypes for STR: ATXN2_CAG were changed from Spinocerebellar ataxia 2 183090 to Spinocerebellar ataxia 2, OMIM:183090
Hereditary ataxia with onset in adulthood v2.99 ATXN2_CAG Arina Puzriakova Phenotypes for STR: ATXN2_CAG were changed from Spinocerebellar ataxia 2 183090 to Spinocerebellar ataxia 2, OMIM:183090
Adult onset dystonia, chorea or related movement disorder v1.131 ATXN2_CAG Arina Puzriakova Phenotypes for STR: ATXN2_CAG were changed from Spinocerebellar ataxia 2 183090 to Spinocerebellar ataxia 2, OMIM:183090; {Amyotrophic lateral sclerosis, susceptibility to, 13}, OMIM:183090; {Parkinson disease, late-onset, susceptibility to}, OMIM:168600
Adult onset dystonia, chorea or related movement disorder v1.130 ATXN2_CAG Arina Puzriakova Tag watchlist tag was added to STR: ATXN2_CAG.
Childhood onset dystonia, chorea or related movement disorder v1.173 ATXN2_CAG Arina Puzriakova Phenotypes for STR: ATXN2_CAG were changed from Spinocerebellar ataxia 2, 183090 to Spinocerebellar ataxia 2, OMIM:183090; {Amyotrophic lateral sclerosis, susceptibility to, 13}, OMIM:183090
Early onset dystonia v1.91 ATXN2_CAG Arina Puzriakova Phenotypes for STR: ATXN2_CAG were changed from Spinocerebellar ataxia 2 183090 to Spinocerebellar ataxia 2, OMIM:183090; {Amyotrophic lateral sclerosis, susceptibility to, 13}, OMIM:183090
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.54 ATXN2_CAG Arina Puzriakova Phenotypes for STR: ATXN2_CAG were changed from Spinocerebellar ataxia 2 183090 to Spinocerebellar ataxia 2, OMIM:183090; {Amyotrophic lateral sclerosis, susceptibility to, 13}, OMIM:183090; {Parkinson disease, late-onset, susceptibility to}, OMIM:168600
Parkinson Disease and Complex Parkinsonism v1.75 ATXN2_CAG Arina Puzriakova Phenotypes for STR: ATXN2_CAG were changed from Spinocerebellar ataxia 2 183090 to {Parkinson disease, late-onset, susceptibility to}, OMIM:168600
Intellectual disability v3.1414 ATXN2 Arina Puzriakova Mode of pathogenicity for gene: ATXN2 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
Adult onset neurodegenerative disorder v2.210 ATXN2 Arina Puzriakova Mode of pathogenicity for gene: ATXN2 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
Adult onset dystonia, chorea or related movement disorder v1.130 ATXN2 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Adult onset dystonia, chorea or related movement disorder v1.130 ATXN2 Arina Puzriakova Mode of inheritance for gene: ATXN2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Other
Hereditary ataxia with onset in adulthood v2.98 ATXN2 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Hereditary ataxia with onset in adulthood v2.98 ATXN2 Arina Puzriakova Mode of inheritance for gene: ATXN2 was changed from Unknown to Other
Intellectual disability v3.1413 ATXN2 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Intellectual disability v3.1413 ATXN2 Arina Puzriakova Mode of inheritance for gene: ATXN2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Other
Amyotrophic lateral sclerosis/motor neuron disease v1.41 ATXN2 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Amyotrophic lateral sclerosis/motor neuron disease v1.41 ATXN2 Arina Puzriakova Mode of inheritance for gene: ATXN2 was changed from to Other
Hereditary ataxia v1.253 ATXN2 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Hereditary ataxia v1.253 ATXN2 Arina Puzriakova Mode of inheritance for gene: ATXN2 was changed from to Other
Ataxia and cerebellar anomalies - narrow panel v2.251 ATXN2 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Ataxia and cerebellar anomalies - narrow panel v2.251 ATXN2 Arina Puzriakova Mode of inheritance for gene: ATXN2 was changed from Unknown to Other
Adult onset neurodegenerative disorder v2.209 ATXN2 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Adult onset neurodegenerative disorder v2.209 ATXN2 Arina Puzriakova Mode of inheritance for gene: ATXN2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Other
Ataxia and cerebellar anomalies - narrow panel v2.250 ATXN2 Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: ATXN2.
Tag currently-ngs-unreportable tag was added to gene: ATXN2.
Hereditary ataxia with onset in adulthood v2.97 ATXN2 Arina Puzriakova Phenotypes for gene: ATXN2 were changed from Spinocerebellarataxia2, 183090; Spinocerebellar ataxia 2, 183090; {Amyotrophiclateralsclerosis,susceptibilityto,13},183090 to Spinocerebellar ataxia 2, OMIM:183090
Adult onset dystonia, chorea or related movement disorder v1.129 ATXN2 Arina Puzriakova Phenotypes for gene: ATXN2 were changed from {Parkinson disease, late-onset, susceptibility to}, 168600; (CAGexpansion); familial parkinsonism; Spinocerebellar ataxia 2, 183190; {Amyotrophic lateral sclerosis, susceptibility to, 13}, 183190 to Spinocerebellar ataxia 2, OMIM:183090; {Amyotrophic lateral sclerosis, susceptibility to, 13}, OMIM:183090; {Parkinson disease, late-onset, susceptibility to}, OMIM:168600
Adult onset dystonia, chorea or related movement disorder v1.128 ATXN2 Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: ATXN2.
Tag currently-ngs-unreportable tag was added to gene: ATXN2.
Intellectual disability v3.1412 ATXN2 Arina Puzriakova Phenotypes for gene: ATXN2 were changed from Spinocerebellar ataxia 2 183090; {Amyotrophic lateral sclerosis, susceptibility to, 13} 183090 to Spinocerebellar ataxia 2, OMIM:183090; {Amyotrophic lateral sclerosis, susceptibility to, 13}, OMIM:183090; {Parkinson disease, late-onset, susceptibility to}, OMIM:168600
Intellectual disability v3.1411 ATXN2 Arina Puzriakova Tag currently-ngs-unreportable tag was added to gene: ATXN2.
Amyotrophic lateral sclerosis/motor neuron disease v1.40 ATXN2 Arina Puzriakova Phenotypes for gene: ATXN2 were changed from Spinocerebellar ataxia 2, 183090; {Amyotrophic lateral sclerosis, susceptibility to, 13}, 183090 to {Amyotrophic lateral sclerosis, susceptibility to, 13}, OMIM:183090
Amyotrophic lateral sclerosis/motor neuron disease v1.39 ATXN2 Arina Puzriakova Tag currently-ngs-unreportable tag was added to gene: ATXN2.
Hereditary ataxia v1.252 ATXN2 Arina Puzriakova Phenotypes for gene: ATXN2 were changed from Spinocerebellarataxia2,183090{Amyotrophiclateralsclerosis,susceptibilityto,13},183090 to Spinocerebellar ataxia 2, OMIM:183090
Ataxia and cerebellar anomalies - narrow panel v2.250 ATXN2 Arina Puzriakova Phenotypes for gene: ATXN2 were changed from Spinocerebellarataxia2,183090{Amyotrophiclateralsclerosis,susceptibilityto,13},183090 to Spinocerebellar ataxia 2, OMIM:183090
Adult onset neurodegenerative disorder v2.208 ATXN2 Arina Puzriakova Phenotypes for gene: ATXN2 were changed from Spinocerebellar ataxia 2, 183090; familial parkinsonism; {Amyotrophic lateral sclerosis, susceptibility to, 13}, 183090; Spinocerebellarataxia2,183090{Amyotrophiclateralsclerosis,susceptibilityto,13},183090; (CAGexpansion) to Spinocerebellar ataxia 2, OMIM:183090; {Amyotrophic lateral sclerosis, susceptibility to, 13}, OMIM:183090; {Parkinson disease, late-onset, susceptibility to}, OMIM:168600
Parkinson Disease and Complex Parkinsonism v1.74 ATXN2 Arina Puzriakova Tag currently-ngs-unreportable tag was added to gene: ATXN2.
Parkinson Disease and Complex Parkinsonism v1.74 ATXN2 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Parkinson Disease and Complex Parkinsonism v1.74 ATXN2 Arina Puzriakova Mode of inheritance for gene: ATXN2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Other
Parkinson Disease and Complex Parkinsonism v1.73 ATXN2 Arina Puzriakova Phenotypes for gene: ATXN2 were changed from (CAGexpansion); familial parkinsonism to {Parkinson disease, late-onset, susceptibility to}, OMIM:168600
Intellectual disability v3.1411 ATXN10_ATTCT Arina Puzriakova Phenotypes for STR: ATXN10_ATTCT were changed from Spinocerebellar ataxia 10 603516 to Spinocerebellar ataxia 10, OMIM:603516
Hereditary ataxia with onset in adulthood v2.96 ATXN10_ATTCT Arina Puzriakova Phenotypes for STR: ATXN10_ATTCT were changed from Spinocerebellar ataxia 10 603516 to Spinocerebellar ataxia 10, OMIM:603516
Hereditary neuropathy v1.419 ATXN10_ATTCT Arina Puzriakova Phenotypes for STR: ATXN10_ATTCT were changed from Spinocerebellar ataxia 10 603516 to Spinocerebellar ataxia 10, OMIM:603516
Adult onset neurodegenerative disorder v2.207 ATXN10_ATTCT Arina Puzriakova Phenotypes for STR: ATXN10_ATTCT were changed from Spinocerebellar ataxia 10 603516 to Spinocerebellar ataxia 10, OMIM:603516
Adult onset neurodegenerative disorder v2.206 ATXN10_ATTCT Arina Puzriakova Tag watchlist tag was added to STR: ATXN10_ATTCT.
Adult onset hereditary spastic paraplegia v1.74 ATXN10_ATTCT Arina Puzriakova Phenotypes for STR: ATXN10_ATTCT were changed from Spinocerebellar ataxia 10 603516 to Spinocerebellar ataxia 10, OMIM:603516
Adult onset hereditary spastic paraplegia v1.73 ATXN10_ATTCT Arina Puzriakova Tag watchlist tag was added to STR: ATXN10_ATTCT.
Skeletal dysplasia v2.151 ATXN10_ATTCT Arina Puzriakova Phenotypes for STR: ATXN10_ATTCT were changed from Spinocerebellar ataxia 10 603516 to Spinocerebellar ataxia 10, OMIM:603516
Childhood onset hereditary spastic paraplegia v2.88 ATXN10_ATTCT Arina Puzriakova Phenotypes for STR: ATXN10_ATTCT were changed from Spinocerebellar ataxia 10 603516 to Spinocerebellar ataxia 10, OMIM:603516
Hereditary spastic paraplegia v1.260 ATXN10_ATTCT Arina Puzriakova Phenotypes for STR: ATXN10_ATTCT were changed from Spinocerebellar ataxia 10 603516 to Spinocerebellar ataxia 10, OMIM:603516
Hereditary ataxia v1.251 ATXN10_ATTCT Arina Puzriakova Phenotypes for STR: ATXN10_ATTCT were changed from Spinocerebellar ataxia 10 603516 to Spinocerebellar ataxia 10, OMIM:603516
Thoracic dystrophies v1.15 ATXN10_ATTCT Arina Puzriakova Phenotypes for STR: ATXN10_ATTCT were changed from Spinocerebellar ataxia 10 603516 to Spinocerebellar ataxia 10, OMIM:603516
Ataxia and cerebellar anomalies - narrow panel v2.249 ATXN10_ATTCT Arina Puzriakova Phenotypes for STR: ATXN10_ATTCT were changed from Spinocerebellar ataxia 10 603516 to Spinocerebellar ataxia 10, OMIM:603516
Ataxia and cerebellar anomalies - narrow panel v2.248 ATXN10_ATTCT Arina Puzriakova Tag watchlist tag was added to STR: ATXN10_ATTCT.
Early onset dystonia v1.90 ATXN10_ATTCT Arina Puzriakova Phenotypes for STR: ATXN10_ATTCT were changed from Spinocerebellar ataxia 10 603516 to Spinocerebellar ataxia 10, OMIM:603516
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.53 ATXN10_ATTCT Arina Puzriakova Phenotypes for STR: ATXN10_ATTCT were changed from Spinocerebellar ataxia 10 603516 to Spinocerebellar ataxia 10, OMIM:603516
Childhood onset dystonia, chorea or related movement disorder v1.172 ATXN10 Arina Puzriakova Mode of pathogenicity for gene: ATXN10 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
Childhood onset dystonia, chorea or related movement disorder v1.171 ATXN10 Arina Puzriakova Classified gene: ATXN10 as Red List (low evidence)
Childhood onset dystonia, chorea or related movement disorder v1.171 ATXN10 Arina Puzriakova Gene: atxn10 has been classified as Red List (Low Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.170 ATXN10 Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: ATXN10.
Tag currently-ngs-unreportable tag was added to gene: ATXN10.
Rare multisystem ciliopathy disorders v1.151 ATXN10 Arina Puzriakova Tag currently-ngs-unreportable tag was added to gene: ATXN10.
Adult onset neurodegenerative disorder v2.206 ATXN10 Arina Puzriakova Tag watchlist was removed from gene: ATXN10.
Skeletal dysplasia v2.150 ATXN10 Arina Puzriakova Tag currently-ngs-unreportable tag was added to gene: ATXN10.
Primary ciliary disorders v1.35 ATXN10 Arina Puzriakova Tag currently-ngs-unreportable tag was added to gene: ATXN10.
Hereditary ataxia v1.250 ATXN10 Arina Puzriakova Tag watchlist was removed from gene: ATXN10.
Thoracic dystrophies v1.14 ATXN10 Arina Puzriakova Tag currently-ngs-unreportable tag was added to gene: ATXN10.
Ataxia and cerebellar anomalies - narrow panel v2.248 ATXN10 Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: ATXN10.
Tag currently-ngs-unreportable tag was added to gene: ATXN10.
Childhood onset dystonia, chorea or related movement disorder v1.170 ATXN10 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Childhood onset dystonia, chorea or related movement disorder v1.170 ATXN10 Arina Puzriakova Mode of inheritance for gene: ATXN10 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Other
Intellectual disability v3.1410 ATXN10 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Intellectual disability v3.1410 ATXN10 Arina Puzriakova Mode of inheritance for gene: ATXN10 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Other
Rare multisystem ciliopathy disorders v1.151 ATXN10 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Rare multisystem ciliopathy disorders v1.151 ATXN10 Arina Puzriakova Mode of inheritance for gene: ATXN10 was changed from to Other
Hereditary ataxia with onset in adulthood v2.95 ATXN10 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Hereditary ataxia with onset in adulthood v2.95 ATXN10 Arina Puzriakova Mode of inheritance for gene: ATXN10 was changed from Unknown to Other
Skeletal dysplasia v2.150 ATXN10 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Skeletal dysplasia v2.150 ATXN10 Arina Puzriakova Mode of inheritance for gene: ATXN10 was changed from to Other
Adult onset neurodegenerative disorder v2.206 ATXN10 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Adult onset neurodegenerative disorder v2.206 ATXN10 Arina Puzriakova Mode of inheritance for gene: ATXN10 was changed from Unknown to Other
Primary ciliary disorders v1.35 ATXN10 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Primary ciliary disorders v1.35 ATXN10 Arina Puzriakova Mode of inheritance for gene: ATXN10 was changed from to Other
Hereditary ataxia v1.250 ATXN10 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Hereditary ataxia v1.250 ATXN10 Arina Puzriakova Mode of inheritance for gene: ATXN10 was changed from to Other
Thoracic dystrophies v1.14 ATXN10 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Thoracic dystrophies v1.14 ATXN10 Arina Puzriakova Mode of inheritance for gene: ATXN10 was changed from to Other
Ataxia and cerebellar anomalies - narrow panel v2.248 ATXN10 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Ataxia and cerebellar anomalies - narrow panel v2.248 ATXN10 Arina Puzriakova Mode of inheritance for gene: ATXN10 was changed from Unknown to Other
Childhood onset dystonia, chorea or related movement disorder v1.169 ATXN10 Arina Puzriakova Phenotypes for gene: ATXN10 were changed from Spinocerebellar ataxia 10, 603516 to Spinocerebellar ataxia 10, OMIM:603516
Rare multisystem ciliopathy disorders v1.150 ATXN10 Arina Puzriakova Phenotypes for gene: ATXN10 were changed from Spinocerebellar ataxia 10, 603516; Ciliopathies to Spinocerebellar ataxia 10, OMIM:603516; Ciliopathies
Hereditary ataxia with onset in adulthood v2.94 ATXN10 Arina Puzriakova Phenotypes for gene: ATXN10 were changed from Spinocerebellar ataxia 10, 603516; Spinocerebellarataxia10, 603516 to Spinocerebellar ataxia 10, OMIM:603516
Intellectual disability v3.1409 ATXN10 Arina Puzriakova Phenotypes for gene: ATXN10 were changed from Spinocerebellar ataxia 10 603516 to Spinocerebellar ataxia 10, OMIM:603516
Adult onset neurodegenerative disorder v2.205 ATXN10 Arina Puzriakova Phenotypes for gene: ATXN10 were changed from Spinocerebellarataxia10,603516 to Spinocerebellar ataxia 10, OMIM:603516
Skeletal dysplasia v2.149 ATXN10 Arina Puzriakova Phenotypes for gene: ATXN10 were changed from to Spinocerebellar ataxia 10, OMIM:603516
Primary ciliary disorders v1.34 ATXN10 Arina Puzriakova Phenotypes for gene: ATXN10 were changed from ciliopathies to Spinocerebellar ataxia 10, OMIM:603516; Ciliopathies
Hereditary ataxia v1.249 ATXN10 Arina Puzriakova Phenotypes for gene: ATXN10 were changed from Spinocerebellarataxia10,603516 to Spinocerebellar ataxia 10, OMIM:603516
Thoracic dystrophies v1.13 ATXN10 Arina Puzriakova Phenotypes for gene: ATXN10 were changed from to Spinocerebellar ataxia 10, OMIM:603516
Ataxia and cerebellar anomalies - narrow panel v2.247 ATXN10 Arina Puzriakova Phenotypes for gene: ATXN10 were changed from Spinocerebellarataxia10,603516 to Spinocerebellar ataxia 10, OMIM:603516
Ataxia and cerebellar anomalies - narrow panel v2.246 ATN1_CAG Arina Puzriakova Tag watchlist tag was added to STR: ATN1_CAG.
Adult onset dystonia, chorea or related movement disorder v1.128 ATN1_CAG Arina Puzriakova Phenotypes for STR: ATN1_CAG were changed from Dentatorubro-pallidoluysian atrophy 125370 to Dentatorubral-pallidoluysian atrophy, OMIM:125370
Hereditary ataxia with onset in adulthood v2.93 ATN1_CAG Arina Puzriakova Phenotypes for STR: ATN1_CAG were changed from Dentatorubro-pallidoluysian atrophy 125370 to Dentatorubral-pallidoluysian atrophy, OMIM:125370
Early onset or syndromic epilepsy v2.459 ATN1_CAG Arina Puzriakova Phenotypes for STR: ATN1_CAG were changed from Dentatorubro-pallidoluysian atrophy 125370 to Dentatorubral-pallidoluysian atrophy, OMIM:125370
Adult onset neurodegenerative disorder v2.204 ATN1_CAG Arina Puzriakova Tag watchlist tag was added to STR: ATN1_CAG.
Adult onset neurodegenerative disorder v2.204 ATN1_CAG Arina Puzriakova Phenotypes for STR: ATN1_CAG were changed from Dentatorubro-pallidoluysian atrophy 125370 to Dentatorubral-pallidoluysian atrophy, OMIM:125370
Paroxysmal central nervous system disorders v1.20 ATN1_CAG Arina Puzriakova Phenotypes for STR: ATN1_CAG were changed from Dentatorubro-pallidoluysian atrophy 125370 to Dentatorubral-pallidoluysian atrophy, OMIM:125370
Hereditary ataxia v1.248 ATN1_CAG Arina Puzriakova Phenotypes for STR: ATN1_CAG were changed from Dentatorubro-pallidoluysian atrophy 125370 to Dentatorubral-pallidoluysian atrophy, OMIM:125370
Ataxia and cerebellar anomalies - narrow panel v2.246 ATN1_CAG Arina Puzriakova Phenotypes for STR: ATN1_CAG were changed from Dentatorubro-pallidoluysian atrophy 125370 to Dentatorubral-pallidoluysian atrophy, OMIM:125370
Brain channelopathy v1.63 ATN1_CAG Arina Puzriakova Phenotypes for STR: ATN1_CAG were changed from Dentatorubro-pallidoluysian atrophy 125370 to Dentatorubral-pallidoluysian atrophy, OMIM:125370
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.52 ATN1_CAG Arina Puzriakova Phenotypes for STR: ATN1_CAG were changed from Dentatorubro-pallidoluysian atrophy 125370 to Dentatorubral-pallidoluysian atrophy, OMIM:125370
Parkinson Disease and Complex Parkinsonism v1.72 ATN1_CAG Arina Puzriakova Phenotypes for STR: ATN1_CAG were changed from Dentatorubro-pallidoluysian atrophy 125370 to Dentatorubral-pallidoluysian atrophy, OMIM:125370
Adult onset neurodegenerative disorder v2.203 ATN1 Arina Puzriakova Phenotypes for gene: ATN1 were changed from Dentatorubro-pallidoluysian atrophy 125370 to Dentatorubral-pallidoluysian atrophy, OMIM:125370
Paroxysmal central nervous system disorders v1.19 ATN1 Arina Puzriakova Phenotypes for gene: ATN1 were changed from Dentatorubro-pallidoluysian atrophy, 125370 to Dentatorubral-pallidoluysian atrophy, OMIM:125370
Brain channelopathy v1.62 ATN1 Arina Puzriakova Phenotypes for gene: ATN1 were changed from Dentatorubro-pallidoluysian atrophy 125370 to Dentatorubral-pallidoluysian atrophy, OMIM:125370
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.51 ATN1 Arina Puzriakova Phenotypes for gene: ATN1 were changed from Dentatorubro-pallidoluysian atrophy 125370 to Dentatorubral-pallidoluysian atrophy, OMIM:125370
Hereditary ataxia v1.247 ATN1 Arina Puzriakova Phenotypes for gene: ATN1 were changed from to Dentatorubral-pallidoluysian atrophy, OMIM:125370
Ataxia and cerebellar anomalies - narrow panel v2.245 ATN1 Arina Puzriakova Phenotypes for gene: ATN1 were changed from to Dentatorubral-pallidoluysian atrophy, OMIM:125370
Childhood onset dystonia, chorea or related movement disorder v1.168 ATN1 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Childhood onset dystonia, chorea or related movement disorder v1.168 ATN1 Arina Puzriakova Mode of inheritance for gene: ATN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to Other
Childhood onset dystonia, chorea or related movement disorder v1.167 ATN1 Arina Puzriakova Phenotypes for gene: ATN1 were changed from Dentatorubro-pallidoluysian atrophy, 125370 to Dentatorubral-pallidoluysian atrophy, OMIM:125370
Childhood onset dystonia, chorea or related movement disorder v1.166 ATN1 Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: ATN1.
Tag currently-ngs-unreportable tag was added to gene: ATN1.
Adult onset dystonia, chorea or related movement disorder v1.127 ATN1 Arina Puzriakova Phenotypes for gene: ATN1 were changed from Dentatorubro-pallidoluysian atrophy 125370 to Dentatorubral-pallidoluysian atrophy, OMIM:125370
Hereditary ataxia with onset in adulthood v2.92 ATN1 Arina Puzriakova Phenotypes for gene: ATN1 were changed from Dentato-pallidoluysian atrophy; Dentatorubro-pallidoluysian atrophy 125370 to Dentatorubral-pallidoluysian atrophy, OMIM:125370
Adult onset dystonia, chorea or related movement disorder v1.126 ATN1 Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: ATN1.
Tag currently-ngs-unreportable tag was added to gene: ATN1.
Adult onset dystonia, chorea or related movement disorder v1.126 ATN1 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Adult onset dystonia, chorea or related movement disorder v1.126 ATN1 Arina Puzriakova Mode of inheritance for gene: ATN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to Other
Hereditary ataxia with onset in adulthood v2.91 ATN1 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Hereditary ataxia with onset in adulthood v2.91 ATN1 Arina Puzriakova Mode of inheritance for gene: ATN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to Other
Hereditary ataxia v1.246 ATN1 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Hereditary ataxia v1.246 ATN1 Arina Puzriakova Mode of inheritance for gene: ATN1 was changed from Other - please specifiy in evaluation comments to Other
Ataxia and cerebellar anomalies - narrow panel v2.244 ATN1 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Ataxia and cerebellar anomalies - narrow panel v2.244 ATN1 Arina Puzriakova Mode of inheritance for gene: ATN1 was changed from Other - please specifiy in evaluation comments to Other
DDG2P v2.52 ATN1 Arina Puzriakova Phenotypes for gene: ATN1 were changed from congenital hypotonia, epilepsy, developmental delay, digit abnormalities to Congenital hypotonia, epilepsy, developmental delay, and digital anomalies, OMIM:618494
Paroxysmal central nervous system disorders v1.18 ATN1 Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: ATN1.
Tag currently-ngs-unreportable tag was added to gene: ATN1.
Ataxia and cerebellar anomalies - narrow panel v2.243 ATN1 Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: ATN1.
Tag currently-ngs-unreportable tag was added to gene: ATN1.
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.50 ATN1 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.50 ATN1 Arina Puzriakova Mode of inheritance for gene: ATN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to Other
Brain channelopathy v1.61 ATN1 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Brain channelopathy v1.61 ATN1 Arina Puzriakova Mode of inheritance for gene: ATN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to Other
Paroxysmal central nervous system disorders v1.18 ATN1 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Paroxysmal central nervous system disorders v1.18 ATN1 Arina Puzriakova Mode of inheritance for gene: ATN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to Other
Adult onset neurodegenerative disorder v2.202 ATN1 Arina Puzriakova changed review comment from: Comment on mode of inheritance: Nucleotide repeat expansion; to: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Adult onset neurodegenerative disorder v2.202 ATN1 Arina Puzriakova Added comment: Comment on mode of inheritance: Nucleotide repeat expansion
Adult onset neurodegenerative disorder v2.202 ATN1 Arina Puzriakova Mode of inheritance for gene: ATN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to Other
Intellectual disability v3.1408 ATN1 Arina Puzriakova Publications for gene: ATN1 were set to 24972706; 30827498
Intellectual disability v3.1407 ATN1 Arina Puzriakova Phenotypes for gene: ATN1 were changed from Generalized hypotonia; Global developmental delay; Intellectual disability; Seizures; Feeding difficulties; Abnormality of the cardiovascular system; Cleft palate; Abnormality of the kidney to Congenital hypotonia, epilepsy, developmental delay, and digital anomalies, OMIM:618494
Early onset or syndromic epilepsy v2.458 ATN1 Arina Puzriakova Phenotypes for gene: ATN1 were changed from Congenital hypotonia, epilepsy, developmental delay, and digital anomalies, 618494; Global developmental delay; Intellectual disability; Seizures; Generalized hypotonia to Congenital hypotonia, epilepsy, developmental delay, and digital anomalies, OMIM:618494
Primary immunodeficiency or monogenic inflammatory bowel disease v2.484 ZNFX1 Sophie Hambleton reviewed gene: ZNFX1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Haematological malignancies cancer susceptibility v2.21 RPS27A Arina Puzriakova Tag pharmacogenetic was removed from gene: RPS27A.
Tag pharmacogenetics tag was added to gene: RPS27A.
Sarcoma cancer susceptibility v1.20 T Arina Puzriakova Tag cnvs was removed from gene: T.
Tag cnv tag was added to gene: T.
Intellectual disability v3.1406 KIDINS220 Dmitrijs Rots reviewed gene: KIDINS220: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 33763417; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary spastic paraplegia v1.259 KIDINS220 Dmitrijs Rots reviewed gene: KIDINS220: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 33763417; Phenotypes: Spastic paraplegia, intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v3.1406 VAMP7 Ivone Leong Tag Pseudoautosomal region 2 tag was added to gene: VAMP7.
Intellectual disability v3.1406 SPRY3 Ivone Leong Tag Pseudoautosomal region 2 tag was added to gene: SPRY3.
Intellectual disability v3.1406 SLC25A6 Ivone Leong Tag Pseudoautosomal region 1 tag was added to gene: SLC25A6.
Skeletal dysplasia v2.148 SHOX Ivone Leong Tag Pseudoautosomal region 1 tag was added to gene: SHOX.
Limb disorders v2.65 SHOX Ivone Leong Tag Pseudoautosomal region 1 tag was added to gene: SHOX.
IUGR and IGF abnormalities v1.41 SHOX Ivone Leong Tag Pseudoautosomal region 1 tag was added to gene: SHOX.
Radial dysplasia v1.15 SHOX Ivone Leong Tag Pseudoautosomal region 1 tag was added to gene: SHOX.
Fetal anomalies v1.793 SHOX Ivone Leong Tag Pseudoautosomal region 1 tag was added to gene: SHOX.
Osteogenesis imperfecta v2.37 SHOX Ivone Leong Tag Pseudoautosomal region 1 tag was added to gene: SHOX.
DDG2P v2.51 SHOX Ivone Leong Tag Pseudoautosomal region 1 tag was added to gene: SHOX.
Intellectual disability v3.1406 SHOX Ivone Leong Tag Pseudoautosomal region 1 tag was added to gene: SHOX.
Intellectual disability v3.1406 PLCXD1 Ivone Leong Tag Pseudoautosomal region 1 tag was added to gene: PLCXD1.
Intellectual disability v3.1406 P2RY8 Ivone Leong Tag Pseudoautosomal region 1 tag was added to gene: P2RY8.
Intellectual disability v3.1406 IL3RA Ivone Leong Tag Pseudoautosomal region 1 tag was added to gene: IL3RA.
Intellectual disability v3.1406 DHRSX Ivone Leong Tag Pseudoautosomal region 1 tag was added to gene: DHRSX.
Intellectual disability v3.1406 CSF2RA Ivone Leong Tag Pseudoautosomal region 1 tag was added to gene: CSF2RA.
Primary immunodeficiency or monogenic inflammatory bowel disease v2.484 CSF2RA Ivone Leong Tag Pseudoautosomal region 1 tag was added to gene: CSF2RA.
Familial pulmonary fibrosis v1.16 CSF2RA Ivone Leong Tag Pseudoautosomal region 1 tag was added to gene: CSF2RA.
COVID-19 research v1.80 CSF2RA Ivone Leong Tag Pseudoautosomal region 1 tag was added to gene: CSF2RA.
Intellectual disability v3.1406 CRLF2 Ivone Leong Tag Pseudoautosomal region 1 tag was added to gene: CRLF2.
Intellectual disability v3.1406 CD99 Ivone Leong Tag Pseudoautosomal region 1 tag was added to gene: CD99.
Intellectual disability v3.1406 ASMTL Ivone Leong Tag Pseudoautosomal region 1 tag was added to gene: ASMTL.
Intellectual disability v3.1406 ASMT Ivone Leong Tag Pseudoautosomal region 1 tag was added to gene: ASMT.
Intellectual disability v3.1406 AKAP17A Ivone Leong Tag Pseudoautosomal region 1 tag was added to gene: AKAP17A.
Fetal anomalies v1.793 RFT1 Ivone Leong Tag for-reivew was removed from gene: RFT1.
Fetal anomalies v1.793 RFT1 Ivone Leong Tag for-review tag was added to gene: RFT1.
Intellectual disability v3.1406 NUP85 Eleanor Williams Classified gene: NUP85 as Amber List (moderate evidence)
Intellectual disability v3.1406 NUP85 Eleanor Williams Added comment: Comment on list classification: Promoting from red to amber. 2 cases reported but degree of ID not confirmed in the second family.
Intellectual disability v3.1406 NUP85 Eleanor Williams Gene: nup85 has been classified as Amber List (Moderate Evidence).
Intellectual disability v3.1405 NUP85 Eleanor Williams changed review comment from: PMID: 34170319 - Ravindran et al 2021 report two pedigrees with an MCPH-SCKS phenotype spectrum without SRNS. In the first family, a 9 yo female, with consanguineous parents, is reported to have a missense variant in NUP85 (c.932G > A; p.R311Q). Intrauterine growth restriction was noticed. At birth microcephaly was observed (OFC < 3rd centile, < −3.6 SD) as well as hypotrophy [weight −2.8 SD), length 45 cm (−2.7 SD), both <3rd centile], facial dysmorphism, syndactyly, long and thin fingers, and bilateral pes adductus. She has severe developmental delay with strongly delayed motor milestones and absent speech. Drug-resistant, genetic epilepsy with focal-onset seizures started in the first year of life. She had no clinical, laboratory or radiological findings indicative of kidney dysfunction

In the second family, compound heterozygous missense variants in NUP85 were detected
(c.1109A > G, c.1589 T > C;p.N370S, p.M530T ) in a fetus. MRI of the fetal brain at 24 + 2 GW indicated complete agenesis of the corpus callosum, abnormal sulcation in the left frontal lobe, nodularity of the frontal horn and trigone with focal puckering of the left lateral ventricle.

PMID: 30179222 - Braun et al 2018 - 2 individuals from the 1 of the families reported with steroid-resistant nephrotic syndrome were also reported to have intellectual disability but showed no structural brain defects. The degree of intellectual disability is not stated. They were found to have 2 compound heterozygous alleles (c.405+1G>A and c.1741G>C, p.Ala581Pro), which segregated from the maternal and the paternal side.
Sources: Literature; to: PMID: 34170319 - Ravindran et al 2021 report two pedigrees with an MCPH-SCKS phenotype spectrum without SRNS. In the first family, a 9 yo female, with consanguineous parents, is reported to have a missense variant in NUP85 (c.932G > A; p.R311Q). Intrauterine growth restriction was noticed. At birth microcephaly was observed (OFC < 3rd centile, < −3.6 SD) as well as hypotrophy [weight −2.8 SD), length 45 cm (−2.7 SD), both <3rd centile], facial dysmorphism, syndactyly, long and thin fingers, and bilateral pes adductus. She has severe developmental delay with strongly delayed motor milestones and absent speech. Drug-resistant, genetic epilepsy with focal-onset seizures started in the first year of life. She had no clinical, laboratory or radiological findings indicative of kidney dysfunction.

In the second family, compound heterozygous missense variants in NUP85 were detected
(c.1109A > G, c.1589 T > C;p.N370S, p.M530T ) in a fetus. MRI of the fetal brain at 24 + 2 GW indicated complete agenesis of the corpus callosum, abnormal sulcation in the left frontal lobe, nodularity of the frontal horn and trigone with focal puckering of the left lateral ventricle.

PMID: 30179222 - Braun et al 2018 - 2 individuals from 1 of the families reported with steroid-resistant nephrotic syndrome were also reported to have intellectual disability but showed no structural brain defects. The degree of intellectual disability is not stated. They were found to have 2 compound heterozygous alleles (c.405+1G>A and c.1741G>C, p.Ala581Pro) in NUP85.
Sources: Literature
Intellectual disability v3.1405 NUP85 Eleanor Williams gene: NUP85 was added
gene: NUP85 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: NUP85 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUP85 were set to 34170319
Phenotypes for gene: NUP85 were set to Primary autosomal recessive microcephaly and Seckel syndrome spectrum disorders (MCPH-SCKS)
Review for gene: NUP85 was set to AMBER
Added comment: PMID: 34170319 - Ravindran et al 2021 report two pedigrees with an MCPH-SCKS phenotype spectrum without SRNS. In the first family, a 9 yo female, with consanguineous parents, is reported to have a missense variant in NUP85 (c.932G > A; p.R311Q). Intrauterine growth restriction was noticed. At birth microcephaly was observed (OFC < 3rd centile, < −3.6 SD) as well as hypotrophy [weight −2.8 SD), length 45 cm (−2.7 SD), both <3rd centile], facial dysmorphism, syndactyly, long and thin fingers, and bilateral pes adductus. She has severe developmental delay with strongly delayed motor milestones and absent speech. Drug-resistant, genetic epilepsy with focal-onset seizures started in the first year of life. She had no clinical, laboratory or radiological findings indicative of kidney dysfunction

In the second family, compound heterozygous missense variants in NUP85 were detected
(c.1109A > G, c.1589 T > C;p.N370S, p.M530T ) in a fetus. MRI of the fetal brain at 24 + 2 GW indicated complete agenesis of the corpus callosum, abnormal sulcation in the left frontal lobe, nodularity of the frontal horn and trigone with focal puckering of the left lateral ventricle.

PMID: 30179222 - Braun et al 2018 - 2 individuals from the 1 of the families reported with steroid-resistant nephrotic syndrome were also reported to have intellectual disability but showed no structural brain defects. The degree of intellectual disability is not stated. They were found to have 2 compound heterozygous alleles (c.405+1G>A and c.1741G>C, p.Ala581Pro), which segregated from the maternal and the paternal side.
Sources: Literature
DDG2P v2.51 EDNRB Ivone Leong Tag Q4_21_MOI tag was added to gene: EDNRB.
DDG2P v2.51 EDNRB Ivone Leong Publications for gene: EDNRB were set to 7778600
DDG2P v2.50 EDNRB Ivone Leong reviewed gene: EDNRB: Rating: ; Mode of pathogenicity: None; Publications: 7778600, 11891690; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal