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Photosensitivity Syndromes v0.11 GATA1 Zornitza Stark Marked gene: GATA1 as ready
Photosensitivity Syndromes v0.11 GATA1 Zornitza Stark Gene: gata1 has been classified as Amber List (Moderate Evidence).
Photosensitivity Syndromes v0.11 GATA1 Zornitza Stark Classified gene: GATA1 as Amber List (moderate evidence)
Photosensitivity Syndromes v0.11 GATA1 Zornitza Stark Gene: gata1 has been classified as Amber List (Moderate Evidence).
Photosensitivity Syndromes v0.10 FECH Zornitza Stark Marked gene: FECH as ready
Photosensitivity Syndromes v0.10 FECH Zornitza Stark Gene: fech has been classified as Green List (High Evidence).
Photosensitivity Syndromes v0.10 FECH Zornitza Stark Classified gene: FECH as Green List (high evidence)
Photosensitivity Syndromes v0.10 FECH Zornitza Stark Gene: fech has been classified as Green List (High Evidence).
Photosensitivity Syndromes v0.9 GATA1 Elena Savva gene: GATA1 was added
gene: GATA1 was added to Photosensitivity Syndromes. Sources: Expert list
Mode of inheritance for gene: GATA1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: GATA1 were set to PMID: 17148589; 25251786
Phenotypes for gene: GATA1 were set to Erythropoietic porphyria
Review for gene: GATA1 was set to AMBER
Added comment: PMID: 17148589 - 1 hemizygous English/French patient with p.R216W and photosensitive bullous dermatosis

PMID: 25251786 - 1 hemizygous Turkish patient with p.R216W and photosensitive bullous dermatosis
Sources: Expert list
Congenital Disorders of Glycosylation v0.96 EOGT Dean Phelan reviewed gene: EOGT: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 23522784, 31368252, 29924900; Phenotypes: scalp aplasia cutis congenita, transverse terminal limb defects; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Photosensitivity Syndromes v0.9 FECH Elena Savva gene: FECH was added
gene: FECH was added to Photosensitivity Syndromes. Sources: Expert list
Mode of inheritance for gene: FECH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FECH were set to PMID: 31304091; 17875872
Phenotypes for gene: FECH were set to Protoporphyria, erythropoietic, 1 177000
Review for gene: FECH was set to GREEN
Added comment: PMID: 31304091 - 1 family (3 patients) with cutaneous photosensitivity and erythropoietic protoporphyria (EPP)

PMID: 17875872 - 11 unrelated patients with Erythropoietic Protoporphyria and acute cutaneous photo-sensitivity. 10/11 were heterozygous for the common variant c.333-48T>C w/ a 2nd mutation.

c.333-48T>C is a common variant with functional studies, but has almost 4000 homozygotes in the population with 35% frequency in Latino and East Asian groups. Most recently classed as pathogenic (ClinVar).
Sources: Expert list
Photosensitivity Syndromes v0.9 PPOX Zornitza Stark Marked gene: PPOX as ready
Photosensitivity Syndromes v0.9 PPOX Zornitza Stark Gene: ppox has been classified as Green List (High Evidence).
Photosensitivity Syndromes v0.9 PPOX Zornitza Stark Classified gene: PPOX as Green List (high evidence)
Photosensitivity Syndromes v0.9 PPOX Zornitza Stark Gene: ppox has been classified as Green List (High Evidence).
Photosensitivity Syndromes v0.8 RECQL4 Zornitza Stark Marked gene: RECQL4 as ready
Photosensitivity Syndromes v0.8 RECQL4 Zornitza Stark Gene: recql4 has been classified as Green List (High Evidence).
Photosensitivity Syndromes v0.8 RECQL4 Zornitza Stark Classified gene: RECQL4 as Green List (high evidence)
Photosensitivity Syndromes v0.8 RECQL4 Zornitza Stark Gene: recql4 has been classified as Green List (High Evidence).
Photosensitivity Syndromes v0.7 CPOX Zornitza Stark Marked gene: CPOX as ready
Photosensitivity Syndromes v0.7 CPOX Zornitza Stark Gene: cpox has been classified as Green List (High Evidence).
Photosensitivity Syndromes v0.7 CPOX Zornitza Stark Classified gene: CPOX as Green List (high evidence)
Photosensitivity Syndromes v0.7 CPOX Zornitza Stark Gene: cpox has been classified as Green List (High Evidence).
Photosensitivity Syndromes v0.6 CPOX Zornitza Stark gene: CPOX was added
gene: CPOX was added to Photosensitivity Syndromes. Sources: Expert list
Mode of inheritance for gene: CPOX was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: CPOX were set to 30828546; 28349448; 23582006; 24156084
Phenotypes for gene: CPOX were set to Coproporphyria 121300; Harderoporphyria 618892
Review for gene: CPOX was set to GREEN
Added comment: PMID: 30828546 - 1 chet patient (missense/inframe deletion) with harderoporphyria and chronic cutaneous photosensitivity.

PMID: 28349448 - 1 het (PTC) neonatal patient with coproporphyria and skin photosensitivity

PMID: 23582006 - 1 het (missense) adult patient with photosensitivity and skin fragility. Incomplete penetrance reported.

PMID: 24156084 - 1 het (PTC) adult patient with coproporphyria
Sources: Expert list
Photosensitivity Syndromes v0.5 UROD Zornitza Stark Marked gene: UROD as ready
Photosensitivity Syndromes v0.5 UROD Zornitza Stark Gene: urod has been classified as Green List (High Evidence).
Photosensitivity Syndromes v0.5 UROD Zornitza Stark Classified gene: UROD as Green List (high evidence)
Photosensitivity Syndromes v0.5 UROD Zornitza Stark Gene: urod has been classified as Green List (High Evidence).
Photosensitivity Syndromes v0.4 ALAS2 Zornitza Stark Marked gene: ALAS2 as ready
Photosensitivity Syndromes v0.4 ALAS2 Zornitza Stark Gene: alas2 has been classified as Green List (High Evidence).
Photosensitivity Syndromes v0.4 ALAS2 Zornitza Stark Classified gene: ALAS2 as Green List (high evidence)
Photosensitivity Syndromes v0.4 ALAS2 Zornitza Stark Gene: alas2 has been classified as Green List (High Evidence).
Haem degradation and bilirubin metabolism defects v0.12 UROS Zornitza Stark Publications for gene: UROS were set to 8829650
Photosensitivity Syndromes v0.3 UROS Zornitza Stark Marked gene: UROS as ready
Photosensitivity Syndromes v0.3 UROS Zornitza Stark Gene: uros has been classified as Green List (High Evidence).
Photosensitivity Syndromes v0.3 UROS Zornitza Stark Classified gene: UROS as Green List (high evidence)
Photosensitivity Syndromes v0.3 UROS Zornitza Stark Gene: uros has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v0.96 SEC23A Paul De Fazio changed review comment from: SEC23A is an essential component of coat protein complex II (COPII)-coated vesicles that transport secretory proteins from the endoplasmic reticulum (ER) to the Golgi complex.

Only one family has been reported (PMID:16980979) with a homozygous missense variant and craniolenticulosutural dysplasia (CLSD), with some functional studies supporting pathogenicity.

The same authors later reported another individual with similar phenotype with a paternally inherited heterozygous missense variant, this variant has 91 hets in gnomAD and the father was unaffected (PMID: 21039434). They suggest digenic inheritance but found no other variants in 3 candidate genes.

Zebrafish models lend some support to the gene-disease association (PMID:16980979, 16980978).

This is the only reference to CDG I can find: Two individuals from the same consanguineous family were found to have biallelic variants in SEC23A and MAN1B1 (PMID: 27148587). Patients presented with carbohydrate-deficient transferrin, tall stature, obesity, macrocephaly, and maloccluded teeth (CLSD individuals present with short stature). Parents were healthy carriers for both variants and an unaffected sibling with tall stature carried the heterozygous variant in SEC23A only. The MAN1B1 variant has been previously associated with CDG and short stature. Normal SEC23A levels were identified for all family members. Pro-COL1A1 secretion was increased in patients and siblings. The authors postulate that the SEC23A variants are contributing to the tall stature in the family due to increased pro-COL1A1 secretion, and that this is a digenic disease, but I'm not very convinced.

This gene is not green in any GEL panels. It is on the Invitae CDG panel.

I don't think there is enough evidence for a gene-disease association let alone association with CDG.; to: SEC23A is an essential component of coat protein complex II (COPII)-coated vesicles that transport secretory proteins from the endoplasmic reticulum (ER) to the Golgi complex.

One family has been reported (PMID:16980979) with a homozygous missense variant and craniolenticulosutural dysplasia (CLSD), with some functional studies supporting pathogenicity.

The same authors later reported another individual with similar phenotype with a paternally inherited heterozygous missense variant, this variant has 91 hets in gnomAD and the father was unaffected (PMID: 21039434). They suggest digenic inheritance but found no other variants in 3 candidate genes.

Zebrafish models lend some support to the gene-disease association (PMID:16980979, 16980978).

This is the only reference to CDG I can find: Two individuals from the same consanguineous family were found to have biallelic variants in SEC23A and MAN1B1 (PMID: 27148587). Patients presented with carbohydrate-deficient transferrin, tall stature, obesity, macrocephaly, and maloccluded teeth (CLSD individuals present with short stature). Parents were healthy carriers for both variants and an unaffected sibling with tall stature carried the heterozygous variant in SEC23A only. The MAN1B1 variant has been previously associated with CDG and short stature. Normal SEC23A levels were identified for all family members. Pro-COL1A1 secretion was increased in patients and siblings. The authors postulate that the SEC23A variants are contributing to the tall stature in the family due to increased pro-COL1A1 secretion, and that this is a digenic disease, but I'm not very convinced.

This gene is not green in any GEL panels. It is on the Invitae CDG panel.

I don't think there is enough evidence for a gene-disease association let alone association with CDG.
Congenital Disorders of Glycosylation v0.96 SEC23A Paul De Fazio reviewed gene: SEC23A: Rating: RED; Mode of pathogenicity: None; Publications: 16980979, 21039434, 16980978, 27148587; Phenotypes: Craniolenticulosutural dysplasia (MIM# 607812); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Photosensitivity Syndromes v0.2 PPOX Crystle Lee gene: PPOX was added
gene: PPOX was added to Photosensitivity Syndromes. Sources: Expert Review
Mode of inheritance for gene: PPOX was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PPOX were set to 12357337; 32247286; 23324528
Phenotypes for gene: PPOX were set to Porphyria variegata (MIM#176200)
Review for gene: PPOX was set to GREEN
Added comment: Photosensitivity is a feature of the condition.

PMID: 12357337: 7 different variants reported in a cohort of 103 Finnish patients; 40% had photosensitivity. One of the variant, I12T present in gnomad (9 hets)
Sources: Expert Review
Congenital Disorders of Glycosylation v0.96 POFUT1 Ain Roesley reviewed gene: POFUT1: Rating: AMBER; Mode of pathogenicity: None; Publications: 23684010, 29452367, 25157627; Phenotypes: Dowling-Degos disease 2 (MIM# 615327); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Photosensitivity Syndromes v0.2 RECQL4 Crystle Lee gene: RECQL4 was added
gene: RECQL4 was added to Photosensitivity Syndromes. Sources: Expert Review
Mode of inheritance for gene: RECQL4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RECQL4 were set to 12838562; 10319867; 20503338; 18716613; 18616953
Phenotypes for gene: RECQL4 were set to Rothmund-Thomson syndrome, type 2, (MIM#268400)
Review for gene: RECQL4 was set to GREEN
Added comment: Sun sensitivity is a feature of RTS (OMIM). Congenital poikiloderma and photosensitivity is a feature of this phenotype. Biallelic variants reported in >5 RTS patients.
Sources: Expert Review
Photosensitivity Syndromes v0.2 UROD Crystle Lee gene: UROD was added
gene: UROD was added to Photosensitivity Syndromes. Sources: Expert Review
Mode of inheritance for gene: UROD was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: UROD were set to 23545314; 30514647
Phenotypes for gene: UROD were set to Porphyria cutanea tarda; Porphyria, hepatoerythropoietic (MIM#176100)
Review for gene: UROD was set to GREEN
Added comment: Photosensitivity is a feature of the phenotype (OMIM). Heterozygous variants cause Porphyria Cutanea Tarda (Type 1 and 2) and biallelic variants result in hepatoerythropoietic porphyria (HEP) (hematologic and severe photosensitive cutaneous manifestations in infancy or childhood)
Sources: Expert Review
Photosensitivity Syndromes v0.2 ALAS2 Elena Savva gene: ALAS2 was added
gene: ALAS2 was added to Photosensitivity Syndromes. Sources: Expert list
Mode of inheritance for gene: ALAS2 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: ALAS2 were set to PMID: 25615817
Phenotypes for gene: ALAS2 were set to Protoporphyria, erythropoietic, X-linked 300752
Mode of pathogenicity for gene: ALAS2 was set to Other
Review for gene: ALAS2 was set to GREEN
Added comment: PMID: 25615817 - 6 unrelated families (9 patients) with protoporphyria a history of photosensitivity, females had a later onset. Protoporphyria is caused by GOF variants in the C-terminal. Females show variable severity in phenotype.
Sources: Expert list
Congenital Disorders of Glycosylation v0.96 SLC26A2 Paul De Fazio changed review comment from: Gene-disease association is well-established (OMIM, PMID:11241838) but I can find no evidence that it plays a role in glycosylation.

SLC26A2 encodes a membrane glycoprotein which functions as a sulfate transporter.

From GeneReviews: "Three autosomal recessive disorders, diastrophic dystrophy (DTD), atelosteogenesis type II (AOII), and achondrogenesis type IB (ACG-IB), all result from defective cartilage proteoglycan sulfation...All of these disorders result from different mutations in the DTD gene (SLC26A2), which encodes a plasma membrane sulfate transporter...the heavy demand for sulfate in bone and cartilage proteoglycan synthesis probably explains why the symptoms are most evident in these locations." (https://www.ncbi.nlm.nih.gov/books/NBK453041/)

SLC26A2 is on the Invitae and Mayo Clinic CDG panels. It is listed as a CDG gene on https://glycosmos.org/gdgdbs/index; to: Gene-disease association is well-established (OMIM, PMID:11241838) but I can find no evidence that it plays a direct role in glycosylation.

SLC26A2 encodes a membrane glycoprotein which functions as a sulfate transporter.

From GeneReviews: "Three autosomal recessive disorders, diastrophic dystrophy (DTD), atelosteogenesis type II (AOII), and achondrogenesis type IB (ACG-IB), all result from defective cartilage proteoglycan sulfation...All of these disorders result from different mutations in the DTD gene (SLC26A2), which encodes a plasma membrane sulfate transporter...the heavy demand for sulfate in bone and cartilage proteoglycan synthesis probably explains why the symptoms are most evident in these locations." (https://www.ncbi.nlm.nih.gov/books/NBK453041/)

SLC26A2 is on the Invitae and Mayo Clinic CDG panels. It is listed as a CDG gene on https://glycosmos.org/gdgdbs/index
Congenital Disorders of Glycosylation v0.96 SLC26A2 Paul De Fazio changed review comment from: Gene-disease association is well-established (OMIM, PMID:11241838) but I can find no evidence that it plays a role in glycosylation.

SLC26A2 encodes a membrane glycoprotein which functions as a sulfate transporter.

From GeneReviews: "Three autosomal recessive disorders, diastrophic dystrophy (DTD), atelosteogenesis type II (AOII), and achondrogenesis type IB (ACG-IB), all result from defective cartilage proteoglycan sulfation." (https://www.ncbi.nlm.nih.gov/books/NBK1939/)

SLC26A2 is on the Invitae and Mayo Clinic CDG panels. It is listed as a CDG gene on https://glycosmos.org/gdgdbs/index; to: Gene-disease association is well-established (OMIM, PMID:11241838) but I can find no evidence that it plays a role in glycosylation.

SLC26A2 encodes a membrane glycoprotein which functions as a sulfate transporter.

From GeneReviews: "Three autosomal recessive disorders, diastrophic dystrophy (DTD), atelosteogenesis type II (AOII), and achondrogenesis type IB (ACG-IB), all result from defective cartilage proteoglycan sulfation...All of these disorders result from different mutations in the DTD gene (SLC26A2), which encodes a plasma membrane sulfate transporter...the heavy demand for sulfate in bone and cartilage proteoglycan synthesis probably explains why the symptoms are most evident in these locations." (https://www.ncbi.nlm.nih.gov/books/NBK453041/)

SLC26A2 is on the Invitae and Mayo Clinic CDG panels. It is listed as a CDG gene on https://glycosmos.org/gdgdbs/index
Congenital Disorders of Glycosylation v0.96 SLC26A2 Paul De Fazio changed review comment from: Gene-disease association is well-established (OMIM, PMID:11241838) but I can find no evidence that it plays a role in glycosylation.

SLC26A2 encodes a membrane glycoprotein which functions as a sulfate transporter.

From GeneReviews: "Three autosomal recessive disorders, diastrophic dystrophy (DTD), atelosteogenesis type II (AOII), and achondrogenesis type IB (ACG-IB), all result from defective cartilage proteoglycan sulfation."(https://www.ncbi.nlm.nih.gov/books/NBK1939/)

SLC26A2 is on the Invitae and Mayo Clinic CDG panels. It is listed as a CDG gene on https://glycosmos.org/gdgdbs/index; to: Gene-disease association is well-established (OMIM, PMID:11241838) but I can find no evidence that it plays a role in glycosylation.

SLC26A2 encodes a membrane glycoprotein which functions as a sulfate transporter.

From GeneReviews: "Three autosomal recessive disorders, diastrophic dystrophy (DTD), atelosteogenesis type II (AOII), and achondrogenesis type IB (ACG-IB), all result from defective cartilage proteoglycan sulfation." (https://www.ncbi.nlm.nih.gov/books/NBK1939/)

SLC26A2 is on the Invitae and Mayo Clinic CDG panels. It is listed as a CDG gene on https://glycosmos.org/gdgdbs/index
Haem degradation and bilirubin metabolism defects v0.11 UROS Crystle Lee reviewed gene: UROS: Rating: GREEN; Mode of pathogenicity: None; Publications: 28334762, 27512208; Phenotypes: Porphyria, congenital erythropoietic (MIM#263700); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Photosensitivity Syndromes v0.2 UROS Crystle Lee gene: UROS was added
gene: UROS was added to Photosensitivity Syndromes. Sources: Expert Review
Mode of inheritance for gene: UROS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UROS were set to 28334762; 27512208
Phenotypes for gene: UROS were set to Porphyria, congenital erythropoietic (MIM#263700)
Review for gene: UROS was set to GREEN
Added comment: >10 missense variants reported in CEP patients. Photosensitivity is a significant feature of this phenotype.

PMID: 28334762: Performed in silico and in vitro studies on 29 missense variants previously reported in patients.
Sources: Expert Review
Congenital Disorders of Glycosylation v0.96 SLC26A2 Paul De Fazio reviewed gene: SLC26A2: Rating: AMBER; Mode of pathogenicity: None; Publications: 11241838; Phenotypes: Skeletal dysplasia (various); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Photosensitivity Syndromes v0.2 UVSSA Zornitza Stark Marked gene: UVSSA as ready
Photosensitivity Syndromes v0.2 UVSSA Zornitza Stark Gene: uvssa has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v0.96 MAGT1 Ain Roesley Deleted their comment
Congenital Disorders of Glycosylation v0.96 MAGT1 Ain Roesley edited their review of gene: MAGT1: Added comment: PMID: 31036665;
- 3 affecteds (males; 2x CDG and 1x XMEN)
- All 3 patients have an N-glycosylation defect

PMID: 31714901;
- 23 XMEN patients from 17 families
- glycoproteomic analysis on T cells from 3 patients with XMEN showed defective glycosylation; Changed publications: 31036665, 31714901; Changed phenotypes: Congenital disorder of glycosylation, type Icc (MIM# 301031), Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection and neoplasia (MIM# 300853)
Photosensitivity Syndromes v0.2 UVSSA Zornitza Stark Classified gene: UVSSA as Green List (high evidence)
Photosensitivity Syndromes v0.2 UVSSA Zornitza Stark Gene: uvssa has been classified as Green List (High Evidence).
Mendeliome v0.3442 UVSSA Crystle Lee reviewed gene: UVSSA: Rating: GREEN; Mode of pathogenicity: None; Publications: 31421932; Phenotypes: UV-sensitive syndrome 3 (MIM#614640); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Photosensitivity Syndromes v0.1 UVSSA Crystle Lee gene: UVSSA was added
gene: UVSSA was added to Photosensitivity Syndromes. Sources: Expert Review
Mode of inheritance for gene: UVSSA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UVSSA were set to 31421932
Phenotypes for gene: UVSSA were set to UV-sensitive syndrome 3 (MIM#614640)
Review for gene: UVSSA was set to GREEN
Added comment: At least 4 different variants have previously been reported. The condition is characterised by photosensitivity, and hyperpigmentation, freckling, and dryness of sun exposed areas

PMID: 31421932: Single nonsense variant reported in 2 Pakistani families with UV-sensitive syndrome. Also reviews previously published variants.
Sources: Expert Review
Congenital Disorders of Glycosylation v0.96 MAGT1 Ain Roesley gene: MAGT1 was added
gene: MAGT1 was added to Congenital Disorders of Glycosylation. Sources: Literature
Mode of inheritance for gene: MAGT1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: MAGT1 were set to PMID: 31036665
Phenotypes for gene: MAGT1 were set to Congenital disorder of glycosylation, type Icc (MIM# 301031); Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection and neoplasia (MIM# 300853)
Penetrance for gene: MAGT1 were set to unknown
Review for gene: MAGT1 was set to GREEN
Added comment: PMID: 31036665;
- 3 affecteds (males; 2x CDG and 1x XMEN)
- All 3 patients have an N-glycosylation defect
Sources: Literature
Congenital Disorders of Glycosylation v0.96 SLC35A2 Paul De Fazio changed review comment from: Summary: gene-disease association is well-established. Phenotypes are mostly CNS related. Only a minority have abnormal transferrin glycosylation (10/53 reported individuals according to PMID: 30817854).

3 unrelated individuals with de novo variants reported in PMID:23561849, 2 males and 1 female. The males were mosaic. "In infancy, the commonly used biomarker transferrin showed abnormal glycosylation, but its appearance became normal later in childhood, without any corresponding clinical improvement."

4 unrelated girls with de novo variants and early onset epileptic encephalopathy reported in PMID:24115232 and PMID:27743886. None showed abnormal glycosylation although 'favourable X-inactivation skewing' was noted for some. One more girl with a de novo variant and defective galactosylation of N‐glycans, developmental delay, muscular hypotonia, epileptic seizures, inverted nipples, and visual impairment was described in PMID:25778940.

PMID:30817854 describes another 30 individuals with de novo variants. Only 1 was male (not apparently mosaic), and only 4 had abnormal carbohydrate deficient transferrin.; to: Summary: gene-disease association is well-established. Phenotypes are mostly CNS related (epilepsy, dev delay, etc). Only a minority have abnormal transferrin glycosylation (10/53 reported individuals according to PMID: 30817854).

3 unrelated individuals with de novo variants reported in PMID:23561849, 2 males and 1 female. The males were mosaic. "In infancy, the commonly used biomarker transferrin showed abnormal glycosylation, but its appearance became normal later in childhood, without any corresponding clinical improvement."

4 unrelated girls with de novo variants and early onset epileptic encephalopathy reported in PMID:24115232 and PMID:27743886. None showed abnormal glycosylation although 'favourable X-inactivation skewing' was noted for some. One more girl with a de novo variant and defective galactosylation of N‐glycans, developmental delay, muscular hypotonia, epileptic seizures, inverted nipples, and visual impairment was described in PMID:25778940.

PMID:30817854 describes another 30 individuals with de novo variants. Only 1 was male (not apparently mosaic), and only 4 had abnormal carbohydrate deficient transferrin.
Congenital Disorders of Glycosylation v0.96 SLC35A2 Paul De Fazio changed review comment from: 3 unrelated individuals with de novo variants reported in PMID:23561849, 2 males and 1 female. The males were mosaic. "In infancy, the commonly used biomarker transferrin showed abnormal glycosylation, but its appearance became normal later in childhood, without any corresponding clinical improvement."

4 unrelated girls with de novo variants and early onset epileptic encephalopathy reported in PMID:24115232 and PMID:27743886. None showed abnormal glycosylation although 'favourable X-inactivation skewing' was noted for some. One more girl with a de novo variant and defective galactosylation of N‐glycans, developmental delay, muscular hypotonia, epileptic seizures, inverted nipples, and visual impairment was described in PMID:25778940.

PMID:30817854 describes another 30 individuals with de novo variants. Only 1 was male (not apparently mosaic), and only 4 had abnormal carbohydrate deficient transferrin.; to: Summary: gene-disease association is well-established. Phenotypes are mostly CNS related. Only a minority have abnormal transferrin glycosylation (10/53 reported individuals according to PMID: 30817854).

3 unrelated individuals with de novo variants reported in PMID:23561849, 2 males and 1 female. The males were mosaic. "In infancy, the commonly used biomarker transferrin showed abnormal glycosylation, but its appearance became normal later in childhood, without any corresponding clinical improvement."

4 unrelated girls with de novo variants and early onset epileptic encephalopathy reported in PMID:24115232 and PMID:27743886. None showed abnormal glycosylation although 'favourable X-inactivation skewing' was noted for some. One more girl with a de novo variant and defective galactosylation of N‐glycans, developmental delay, muscular hypotonia, epileptic seizures, inverted nipples, and visual impairment was described in PMID:25778940.

PMID:30817854 describes another 30 individuals with de novo variants. Only 1 was male (not apparently mosaic), and only 4 had abnormal carbohydrate deficient transferrin.
Congenital Disorders of Glycosylation v0.96 SLC35A2 Paul De Fazio reviewed gene: SLC35A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23561849, 24115232, 27743886, 25778940, 30817854; Phenotypes: Congenital disorder of glycosylation, type IIm (MIM #300896); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males); Current diagnostic: yes
Congenital Disorders of Glycosylation v0.96 GMPPA Ain Roesley reviewed gene: GMPPA: Rating: GREEN; Mode of pathogenicity: None; Publications: 24035193, 28574218; Phenotypes: Alacrima, achalasia, and mental retardation syndrome (MIM# 615510); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.96 DSE Ain Roesley reviewed gene: DSE: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 23704329; Phenotypes: Ehlers-Danlos syndrome, musculocontractural type 2 (MIM# 615539); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3441 FAM92A Zornitza Stark Marked gene: FAM92A as ready
Mendeliome v0.3441 FAM92A Zornitza Stark Gene: fam92a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3441 FAM92A Zornitza Stark Classified gene: FAM92A as Amber List (moderate evidence)
Mendeliome v0.3441 FAM92A Zornitza Stark Gene: fam92a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3440 FAM92A Zornitza Stark gene: FAM92A was added
gene: FAM92A was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: FAM92A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAM92A were set to 30395363
Phenotypes for gene: FAM92A were set to Polydactyly, postaxial, type A9, MIM# 618219
Review for gene: FAM92A was set to AMBER
Added comment: Single family and a mouse model reported.
Sources: Expert list
Polydactyly v0.166 FAM92A Zornitza Stark Marked gene: FAM92A as ready
Polydactyly v0.166 FAM92A Zornitza Stark Gene: fam92a has been classified as Amber List (Moderate Evidence).
Polydactyly v0.166 FAM92A Zornitza Stark Classified gene: FAM92A as Amber List (moderate evidence)
Polydactyly v0.166 FAM92A Zornitza Stark Gene: fam92a has been classified as Amber List (Moderate Evidence).
Polydactyly v0.165 FAM92A Zornitza Stark gene: FAM92A was added
gene: FAM92A was added to Polydactyly. Sources: Expert list
Mode of inheritance for gene: FAM92A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAM92A were set to 30395363
Phenotypes for gene: FAM92A were set to Polydactyly, postaxial, type A9, MIM# 618219
Review for gene: FAM92A was set to AMBER
Added comment: Single family and a mouse model reported.
Sources: Expert list
Mendeliome v0.3439 KIAA0825 Zornitza Stark Marked gene: KIAA0825 as ready
Mendeliome v0.3439 KIAA0825 Zornitza Stark Gene: kiaa0825 has been classified as Green List (High Evidence).
Mendeliome v0.3439 KIAA0825 Zornitza Stark Classified gene: KIAA0825 as Green List (high evidence)
Mendeliome v0.3439 KIAA0825 Zornitza Stark Gene: kiaa0825 has been classified as Green List (High Evidence).
Mendeliome v0.3438 KIAA0825 Zornitza Stark gene: KIAA0825 was added
gene: KIAA0825 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KIAA0825 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIAA0825 were set to 32147526; 30982135
Phenotypes for gene: KIAA0825 were set to Polydactyly, postaxial, type A10, MIM# 618498
Review for gene: KIAA0825 was set to GREEN
Added comment: Three unrelated families reported.
Sources: Literature
Polydactyly v0.164 KIAA0825 Zornitza Stark Marked gene: KIAA0825 as ready
Polydactyly v0.164 KIAA0825 Zornitza Stark Gene: kiaa0825 has been classified as Green List (High Evidence).
Polydactyly v0.164 KIAA0825 Zornitza Stark Classified gene: KIAA0825 as Green List (high evidence)
Polydactyly v0.164 KIAA0825 Zornitza Stark Gene: kiaa0825 has been classified as Green List (High Evidence).
Polydactyly v0.163 KIAA0825 Zornitza Stark gene: KIAA0825 was added
gene: KIAA0825 was added to Polydactyly. Sources: Literature
Mode of inheritance for gene: KIAA0825 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIAA0825 were set to 32147526; 30982135
Phenotypes for gene: KIAA0825 were set to Polydactyly, postaxial, type A10, MIM# 618498
Review for gene: KIAA0825 was set to GREEN
Added comment: Three unrelated families reported.
Sources: Literature
Polydactyly v0.162 ZSWIM6 Zornitza Stark Mode of inheritance for gene: ZSWIM6 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3437 ZNF141 Zornitza Stark Marked gene: ZNF141 as ready
Mendeliome v0.3437 ZNF141 Zornitza Stark Gene: znf141 has been classified as Red List (Low Evidence).
Mendeliome v0.3437 ZNF141 Zornitza Stark Phenotypes for gene: ZNF141 were changed from to Polydactyly, postaxial, type A6, MIM# 615226
Mendeliome v0.3436 ZNF141 Zornitza Stark Publications for gene: ZNF141 were set to
Mendeliome v0.3435 ZNF141 Zornitza Stark Mode of inheritance for gene: ZNF141 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3434 ZNF141 Zornitza Stark Classified gene: ZNF141 as Red List (low evidence)
Mendeliome v0.3434 ZNF141 Zornitza Stark Gene: znf141 has been classified as Red List (Low Evidence).
Mendeliome v0.3433 ZNF141 Zornitza Stark reviewed gene: ZNF141: Rating: RED; Mode of pathogenicity: None; Publications: 23160277; Phenotypes: Polydactyly, postaxial, type A6, MIM# 615226; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.161 ZNF141 Zornitza Stark Marked gene: ZNF141 as ready
Polydactyly v0.161 ZNF141 Zornitza Stark Gene: znf141 has been classified as Red List (Low Evidence).
Polydactyly v0.161 ZNF141 Zornitza Stark Publications for gene: ZNF141 were set to
Polydactyly v0.160 ZNF141 Zornitza Stark Phenotypes for gene: ZNF141 were changed from to Polydactyly, postaxial, type A6, MIM# 615226
Polydactyly v0.159 ZNF141 Zornitza Stark Classified gene: ZNF141 as Red List (low evidence)
Polydactyly v0.159 ZNF141 Zornitza Stark Gene: znf141 has been classified as Red List (Low Evidence).
Polydactyly v0.158 ZNF141 Zornitza Stark reviewed gene: ZNF141: Rating: RED; Mode of pathogenicity: None; Publications: 23160277; Phenotypes: Polydactyly, postaxial, type A6, MIM# 615226; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.158 ZNF141 Zornitza Stark Mode of inheritance for gene: ZNF141 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.157 WNT7A Zornitza Stark Mode of inheritance for gene: WNT7A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.156 WDR60 Zornitza Stark Mode of inheritance for gene: WDR60 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.155 WDR35 Zornitza Stark Mode of inheritance for gene: WDR35 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.154 WDR34 Zornitza Stark Mode of inheritance for gene: WDR34 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.153 WDR19 Zornitza Stark Mode of inheritance for gene: WDR19 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.152 WDPCP Zornitza Stark Marked gene: WDPCP as ready
Polydactyly v0.152 WDPCP Zornitza Stark Gene: wdpcp has been classified as Green List (High Evidence).
Polydactyly v0.152 WDPCP Zornitza Stark Mode of inheritance for gene: WDPCP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.151 USP9X Zornitza Stark reviewed gene: USP9X: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mental retardation, X-linked 99, syndromic, female-restricted, MIM# 300968; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Polydactyly v0.151 USP9X Zornitza Stark Marked gene: USP9X as ready
Polydactyly v0.151 USP9X Zornitza Stark Gene: usp9x has been classified as Green List (High Evidence).
Polydactyly v0.151 USP9X Zornitza Stark Phenotypes for gene: USP9X were changed from to Mental retardation, X-linked 99, syndromic, female-restricted, MIM# 300968
Polydactyly v0.150 USP9X Zornitza Stark Mode of inheritance for gene: USP9X was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Polydactyly v0.149 UBE3B Zornitza Stark Mode of inheritance for gene: UBE3B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.148 TWIST1 Zornitza Stark Marked gene: TWIST1 as ready
Polydactyly v0.148 TWIST1 Zornitza Stark Gene: twist1 has been classified as Green List (High Evidence).
Polydactyly v0.148 TWIST1 Zornitza Stark Phenotypes for gene: TWIST1 were changed from to Robinow-Sorauf syndrome, MIM# 180750
Polydactyly v0.147 TWIST1 Zornitza Stark reviewed gene: TWIST1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Robinow-Sorauf syndrome, MIM# 180750; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.147 TWIST1 Zornitza Stark Mode of inheritance for gene: TWIST1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.146 TTC8 Zornitza Stark Mode of inheritance for gene: TTC8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.145 TTC21B Zornitza Stark Mode of inheritance for gene: TTC21B was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Polydactyly v0.144 TRAF3IP1 Zornitza Stark Mode of inheritance for gene: TRAF3IP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.143 TMEM67 Zornitza Stark Mode of inheritance for gene: TMEM67 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.142 TMEM237 Zornitza Stark Mode of inheritance for gene: TMEM237 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.141 TMEM231 Zornitza Stark Mode of inheritance for gene: TMEM231 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.140 TMEM216 Zornitza Stark Mode of inheritance for gene: TMEM216 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.139 TMEM138 Zornitza Stark Mode of inheritance for gene: TMEM138 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.138 TFAP2B Zornitza Stark Mode of inheritance for gene: TFAP2B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.137 TFAP2A Zornitza Stark Mode of inheritance for gene: TFAP2A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.136 TCTN3 Zornitza Stark Mode of inheritance for gene: TCTN3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.135 TCTN2 Zornitza Stark Mode of inheritance for gene: TCTN2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.134 TCTEX1D2 Zornitza Stark Mode of inheritance for gene: TCTEX1D2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.133 TBX5 Zornitza Stark Mode of inheritance for gene: TBX5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.132 TBX3 Zornitza Stark Mode of inheritance for gene: TBX3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.131 TBX22 Zornitza Stark Mode of inheritance for gene: TBX22 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Polydactyly v0.130 SPINT2 Zornitza Stark Mode of inheritance for gene: SPINT2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.129 SMOC1 Zornitza Stark Mode of inheritance for gene: SMOC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.128 SHH Zornitza Stark Mode of inheritance for gene: SHH was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.127 SDCCAG8 Zornitza Stark Mode of inheritance for gene: SDCCAG8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.126 SC5D Zornitza Stark Mode of inheritance for gene: SC5D was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.125 SALL4 Zornitza Stark Mode of inheritance for gene: SALL4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.124 SALL1 Zornitza Stark Mode of inheritance for gene: SALL1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.123 RPGRIP1L Zornitza Stark Mode of inheritance for gene: RPGRIP1L was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.122 RBM10 Zornitza Stark Mode of inheritance for gene: RBM10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.121 RAB23 Zornitza Stark Mode of inheritance for gene: RAB23 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.120 PROM1 Zornitza Stark Marked gene: PROM1 as ready
Polydactyly v0.120 PROM1 Zornitza Stark Gene: prom1 has been classified as Red List (Low Evidence).
Polydactyly v0.120 PROM1 Zornitza Stark Phenotypes for gene: PROM1 were changed from to Cone-rod dystrophy 12, MIM# 612657; Macular dystrophy, retinal, 2, MIM# 608051; Retinitis pigmentosa 41, MIM# 612095; Stargardt disease 4, MIM# 603786
Polydactyly v0.119 PROM1 Zornitza Stark Classified gene: PROM1 as Red List (low evidence)
Polydactyly v0.119 PROM1 Zornitza Stark Gene: prom1 has been classified as Red List (Low Evidence).
Polydactyly v0.118 PROM1 Zornitza Stark reviewed gene: PROM1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Cone-rod dystrophy 12, MIM# 612657, Macular dystrophy, retinal, 2, MIM# 608051, Retinitis pigmentosa 41, MIM# 612095, Stargardt disease 4, MIM# 603786; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Polydactyly v0.118 PROM1 Zornitza Stark Mode of inheritance for gene: PROM1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Polydactyly v0.117 PORCN Zornitza Stark Mode of inheritance for gene: PORCN was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Polydactyly v0.116 PNPLA6 Zornitza Stark Mode of inheritance for gene: PNPLA6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.115 PITX1 Zornitza Stark Mode of inheritance for gene: PITX1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.114 PIK3R2 Zornitza Stark Mode of inheritance for gene: PIK3R2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.113 PIK3CA Zornitza Stark Marked gene: PIK3CA as ready
Polydactyly v0.113 PIK3CA Zornitza Stark Added comment: Comment when marking as ready: Germline variants also described.
Polydactyly v0.113 PIK3CA Zornitza Stark Gene: pik3ca has been classified as Green List (High Evidence).
Polydactyly v0.113 PIK3CA Zornitza Stark Phenotypes for gene: PIK3CA were changed from to Megalencephaly-capillary malformation (MCAP) syndrome , MIM#602501
Polydactyly v0.112 PIK3CA Zornitza Stark Mode of inheritance for gene: PIK3CA was changed from Unknown to Other
Polydactyly v0.111 PIK3CA Zornitza Stark Tag somatic tag was added to gene: PIK3CA.
Polydactyly v0.111 OFD1 Zornitza Stark Mode of inheritance for gene: OFD1 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Polydactyly v0.110 NPHP3 Zornitza Stark Mode of inheritance for gene: NPHP3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.109 NEK1 Zornitza Stark Mode of inheritance for gene: NEK1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.108 MKS1 Zornitza Stark Mode of inheritance for gene: MKS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.107 MKKS Zornitza Stark Mode of inheritance for gene: MKKS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.106 MEGF8 Zornitza Stark Mode of inheritance for gene: MEGF8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.105 MBTPS2 Zornitza Stark Mode of inheritance for gene: MBTPS2 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Polydactyly v0.104 LZTFL1 Zornitza Stark Mode of inheritance for gene: LZTFL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.103 LRP4 Zornitza Stark edited their review of gene: LRP4: Changed phenotypes: Cenani-Lenz syndactyly syndrome, MIM# 212780, Sclerosteosis 2, MIM# 614305
Polydactyly v0.103 LRP4 Zornitza Stark Marked gene: LRP4 as ready
Polydactyly v0.103 LRP4 Zornitza Stark Gene: lrp4 has been classified as Red List (Low Evidence).
Polydactyly v0.103 LRP4 Zornitza Stark edited their review of gene: LRP4: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Polydactyly v0.103 LRP4 Zornitza Stark reviewed gene: LRP4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Polydactyly v0.103 LRP4 Zornitza Stark Classified gene: LRP4 as Red List (low evidence)
Polydactyly v0.103 LRP4 Zornitza Stark Gene: lrp4 has been classified as Red List (Low Evidence).
Polydactyly v0.102 LRP4 Zornitza Stark Mode of inheritance for gene: LRP4 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Polydactyly v0.101 LRP4 Zornitza Stark Phenotypes for gene: LRP4 were changed from to Cenani-Lenz syndactyly syndrome, MIM# 212780; Sclerosteosis 2, MIM# 614305
Polydactyly v0.100 LMBR1 Zornitza Stark Phenotypes for gene: LMBR1 were changed from to Polydactyly, preaxial type II, MIM# 174500
Polydactyly v0.99 LMBR1 Zornitza Stark Mode of inheritance for gene: LMBR1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.98 LBR Zornitza Stark Marked gene: LBR as ready
Polydactyly v0.98 LBR Zornitza Stark Gene: lbr has been classified as Green List (High Evidence).
Polydactyly v0.98 LBR Zornitza Stark Phenotypes for gene: LBR were changed from to Greenberg skeletal dysplasia, MIM# 215140
Polydactyly v0.97 LBR Zornitza Stark Mode of inheritance for gene: LBR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.96 KIF7 Zornitza Stark Mode of inheritance for gene: KIF7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.95 KIAA0586 Zornitza Stark Mode of inheritance for gene: KIAA0586 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.94 INPP5E Zornitza Stark Mode of inheritance for gene: INPP5E was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.93 IFT80 Zornitza Stark Mode of inheritance for gene: IFT80 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.92 IFT52 Zornitza Stark Mode of inheritance for gene: IFT52 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.91 IFT43 Zornitza Stark Mode of inheritance for gene: IFT43 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.90 IFT27 Zornitza Stark Mode of inheritance for gene: IFT27 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.89 IFT172 Zornitza Stark Mode of inheritance for gene: IFT172 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.88 IFT140 Zornitza Stark Mode of inheritance for gene: IFT140 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.87 ICK Zornitza Stark Mode of inheritance for gene: ICK was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Polydactyly v0.86 HYLS1 Zornitza Stark Mode of inheritance for gene: HYLS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.85 HOXD13 Zornitza Stark Phenotypes for gene: HOXD13 were changed from to Synpolydactyly 1, MIM# 186000
Polydactyly v0.84 HOXD13 Zornitza Stark Mode of inheritance for gene: HOXD13 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.83 HOXA13 Zornitza Stark Mode of inheritance for gene: HOXA13 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.82 HNRNPK Zornitza Stark Mode of inheritance for gene: HNRNPK was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.81 GRIP1 Zornitza Stark Mode of inheritance for gene: GRIP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.80 GPC3 Zornitza Stark Mode of inheritance for gene: GPC3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Polydactyly v0.79 GLI3 Zornitza Stark Mode of inheritance for gene: GLI3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.78 GLI2 Zornitza Stark Mode of inheritance for gene: GLI2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.77 GDF5 Zornitza Stark Mode of inheritance for gene: GDF5 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Polydactyly v0.76 FREM2 Zornitza Stark Mode of inheritance for gene: FREM2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.75 FRAS1 Zornitza Stark Mode of inheritance for gene: FRAS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.74 FGFR3 Zornitza Stark Mode of inheritance for gene: FGFR3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.73 FGFR2 Zornitza Stark Mode of inheritance for gene: FGFR2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.72 FGFR1 Zornitza Stark Mode of inheritance for gene: FGFR1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.71 FGF10 Zornitza Stark Mode of inheritance for gene: FGF10 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.70 EVC2 Zornitza Stark Mode of inheritance for gene: EVC2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Polydactyly v0.69 EVC Zornitza Stark Mode of inheritance for gene: EVC was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Polydactyly v0.68 EVC Zornitza Stark Mode of inheritance for gene: EVC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.67 EBP Zornitza Stark Mode of inheritance for gene: EBP was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Polydactyly v0.66 DYNC2LI1 Zornitza Stark Mode of inheritance for gene: DYNC2LI1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.65 DYNC2H1 Zornitza Stark Mode of inheritance for gene: DYNC2H1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.64 DDX59 Zornitza Stark Mode of inheritance for gene: DDX59 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.63 CSPP1 Zornitza Stark Mode of inheritance for gene: CSPP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.62 CKAP2L Zornitza Stark Mode of inheritance for gene: CKAP2L was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.61 CEP41 Zornitza Stark Mode of inheritance for gene: CEP41 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.60 CEP290 Zornitza Stark Mode of inheritance for gene: CEP290 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.59 CEP164 Zornitza Stark Mode of inheritance for gene: CEP164 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.58 CEP120 Zornitza Stark Mode of inheritance for gene: CEP120 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.57 CENPF Zornitza Stark Mode of inheritance for gene: CENPF was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.56 CCND2 Zornitza Stark Mode of inheritance for gene: CCND2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.55 CC2D2A Zornitza Stark Mode of inheritance for gene: CC2D2A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.54 C5orf42 Zornitza Stark Mode of inheritance for gene: C5orf42 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.53 C2CD3 Zornitza Stark Mode of inheritance for gene: C2CD3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.52 BMP4 Zornitza Stark Mode of inheritance for gene: BMP4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.51 BHLHA9 Zornitza Stark Mode of inheritance for gene: BHLHA9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.50 BBS9 Zornitza Stark Mode of inheritance for gene: BBS9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.49 BBS7 Zornitza Stark Mode of inheritance for gene: BBS7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.48 BBS5 Zornitza Stark Mode of inheritance for gene: BBS5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.47 BBS4 Zornitza Stark Mode of inheritance for gene: BBS4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.46 BBS2 Zornitza Stark Mode of inheritance for gene: BBS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.45 BBS12 Zornitza Stark Mode of inheritance for gene: BBS12 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.44 BBS10 Zornitza Stark Marked gene: BBS10 as ready
Polydactyly v0.44 BBS10 Zornitza Stark Gene: bbs10 has been classified as Green List (High Evidence).
Polydactyly v0.44 BBS10 Zornitza Stark Mode of inheritance for gene: BBS10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.43 BBS1 Zornitza Stark Marked gene: BBS1 as ready
Polydactyly v0.43 BBS1 Zornitza Stark Gene: bbs1 has been classified as Green List (High Evidence).
Polydactyly v0.43 BBS1 Zornitza Stark Phenotypes for gene: BBS1 were changed from to Bardet-Biedl syndrome 1, MIM# 209900
Polydactyly v0.42 BBS1 Zornitza Stark Mode of inheritance for gene: BBS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.41 ARL6 Zornitza Stark Marked gene: ARL6 as ready
Polydactyly v0.41 ARL6 Zornitza Stark Gene: arl6 has been classified as Green List (High Evidence).
Polydactyly v0.41 ARL6 Zornitza Stark Mode of inheritance for gene: ARL6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.40 AKT3 Zornitza Stark Marked gene: AKT3 as ready
Polydactyly v0.40 AKT3 Zornitza Stark Gene: akt3 has been classified as Green List (High Evidence).
Polydactyly v0.40 AKT3 Zornitza Stark Phenotypes for gene: AKT3 were changed from to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2, MIM# 615937
Polydactyly v0.39 AKT3 Zornitza Stark Mode of inheritance for gene: AKT3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.38 AHI1 Zornitza Stark Marked gene: AHI1 as ready
Polydactyly v0.38 AHI1 Zornitza Stark Gene: ahi1 has been classified as Green List (High Evidence).
Polydactyly v0.38 AHI1 Zornitza Stark Phenotypes for gene: AHI1 were changed from to Joubert syndrome 3, MIM# 608629
Polydactyly v0.37 AHI1 Zornitza Stark Mode of inheritance for gene: AHI1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.367 Zornitza Stark Panel name changed from Deafness_ComplexAndIsolated to Deafness_IsolatedAndComplex
Deafness_IsolatedAndComplex v0.366 Zornitza Stark Panel name changed from Deafness to Deafness_ComplexAndIsolated
Deafness_Isolated v0.2 Zornitza Stark Panel name changed from DeafnessIsolated to Deafness_Isolated
Deafness_Isolated v0.1 Zornitza Stark Panel status changed from internal to public
Panel types changed to Victorian Clinical Genetics Services; Rare Disease
Deafness_Isolated v0.0 WHRN Zornitza Stark gene: WHRN was added
gene: WHRN was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: WHRN was set to Unknown
Deafness_Isolated v0.0 WBP2 Zornitza Stark gene: WBP2 was added
gene: WBP2 was added to DeafnessIsolated. Sources: Expert Review Amber,Expert list
Mode of inheritance for gene: WBP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WBP2 were set to 26881968
Phenotypes for gene: WBP2 were set to Deafness, autosomal recessive 107, MIM# 617639
Deafness_Isolated v0.0 TOP2B Zornitza Stark gene: TOP2B was added
gene: TOP2B was added to DeafnessIsolated. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: TOP2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TOP2B were set to 31198993
Phenotypes for gene: TOP2B were set to Autosomal dominant deafness
Deafness_Isolated v0.0 TNC Zornitza Stark gene: TNC was added
gene: TNC was added to DeafnessIsolated. Sources: Expert Review Amber,Melbourne Genomics Health Alliance Deafness Flagship,Victorian Clinical Genetics Services
Mode of inheritance for gene: TNC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TNC were set to 23936043
Phenotypes for gene: TNC were set to Deafness, autosomal dominant 56, MIM# 615629
Deafness_Isolated v0.0 TMTC2 Zornitza Stark gene: TMTC2 was added
gene: TMTC2 was added to DeafnessIsolated. Sources: Expert Review Amber,Melbourne Genomics Health Alliance Deafness Flagship,Victorian Clinical Genetics Services
Mode of inheritance for gene: TMTC2 was set to Unknown
Deafness_Isolated v0.0 TMEM132E Zornitza Stark gene: TMEM132E was added
gene: TMEM132E was added to DeafnessIsolated. Sources: Expert Review Amber,Expert list
Mode of inheritance for gene: TMEM132E was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM132E were set to 25331638
Phenotypes for gene: TMEM132E were set to Deafness, autosomal recessive 99, MIM# 618481
Deafness_Isolated v0.0 SPNS2 Zornitza Stark gene: SPNS2 was added
gene: SPNS2 was added to DeafnessIsolated. Sources: Expert Review Amber,Expert list
Mode of inheritance for gene: SPNS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPNS2 were set to 30973865; 25356849
Phenotypes for gene: SPNS2 were set to Deafness, autosomal recessive 115, MIM# 618457
Deafness_Isolated v0.0 SPATC1L Zornitza Stark gene: SPATC1L was added
gene: SPATC1L was added to DeafnessIsolated. Sources: Expert Review Amber,Expert list
Mode of inheritance for gene: SPATC1L was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SPATC1L were set to 30177775
Phenotypes for gene: SPATC1L were set to Deafness
Deafness_Isolated v0.0 SNAI2 Zornitza Stark gene: SNAI2 was added
gene: SNAI2 was added to DeafnessIsolated. Sources: Expert Review Amber,Melbourne Genomics Health Alliance Deafness Flagship,Victorian Clinical Genetics Services
Mode of inheritance for gene: SNAI2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNAI2 were set to 30936914; 12444107
Phenotypes for gene: SNAI2 were set to Waardenburg syndrome, type 2D, MIM# 608890
Deafness_Isolated v0.0 ROR1 Zornitza Stark gene: ROR1 was added
gene: ROR1 was added to DeafnessIsolated. Sources: Expert Review Amber,Expert list
Mode of inheritance for gene: ROR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ROR1 were set to 27162350
Phenotypes for gene: ROR1 were set to Deafness, autosomal recessive 108, MIM# 617654
Deafness_Isolated v0.0 RIPOR2 Zornitza Stark gene: RIPOR2 was added
gene: RIPOR2 was added to DeafnessIsolated. Sources: Expert Review Amber,Expert list
Mode of inheritance for gene: RIPOR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RIPOR2 were set to 24958875
Phenotypes for gene: RIPOR2 were set to Deafness, autosomal recessive 104, MIM# 616515
Deafness_Isolated v0.0 PPIP5K2 Zornitza Stark gene: PPIP5K2 was added
gene: PPIP5K2 was added to DeafnessIsolated. Sources: Expert Review Amber,Expert list
Mode of inheritance for gene: PPIP5K2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPIP5K2 were set to 29590114
Phenotypes for gene: PPIP5K2 were set to Deafness, autosomal recessive 100, MIM# 618422
Deafness_Isolated v0.0 MIR96 Zornitza Stark gene: MIR96 was added
gene: MIR96 was added to DeafnessIsolated. Sources: Expert Review Amber,Melbourne Genomics Health Alliance Deafness Flagship,Victorian Clinical Genetics Services
Mode of inheritance for gene: MIR96 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MIR96 were set to 19363479; 29325119
Phenotypes for gene: MIR96 were set to Deafness, autosomal dominant 50, MIM# 613074
Deafness_Isolated v0.0 LMX1A Zornitza Stark gene: LMX1A was added
gene: LMX1A was added to DeafnessIsolated. Sources: Expert Review Amber,Melbourne Genomics Health Alliance Deafness Flagship,Victorian Clinical Genetics Services
Mode of inheritance for gene: LMX1A was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: LMX1A were set to 29971487; 29754270
Phenotypes for gene: LMX1A were set to Deafness, autosomal recessive and autosomal dominant
Deafness_Isolated v0.0 KITLG Zornitza Stark gene: KITLG was added
gene: KITLG was added to DeafnessIsolated. Sources: Expert Review Amber,Expert list
Mode of inheritance for gene: KITLG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KITLG were set to 26522471
Phenotypes for gene: KITLG were set to Deafness, autosomal dominant 69, unilateral or asymmetric, MIM# 616697
Deafness_Isolated v0.0 GRXCR2 Zornitza Stark gene: GRXCR2 was added
gene: GRXCR2 was added to DeafnessIsolated. Sources: Expert Review Amber,Melbourne Genomics Health Alliance Deafness Flagship,Victorian Clinical Genetics Services
Mode of inheritance for gene: GRXCR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GRXCR2 were set to 24619944
Phenotypes for gene: GRXCR2 were set to Deafness, autosomal recessive 101, MIM# 615837
Deafness_Isolated v0.0 ESRP1 Zornitza Stark gene: ESRP1 was added
gene: ESRP1 was added to DeafnessIsolated. Sources: Expert Review Amber,Expert list
Mode of inheritance for gene: ESRP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ESRP1 were set to 29107558
Phenotypes for gene: ESRP1 were set to Deafness, autosomal recessive 109, MIM# 618013
Deafness_Isolated v0.0 ELMOD3 Zornitza Stark gene: ELMOD3 was added
gene: ELMOD3 was added to DeafnessIsolated. Sources: Expert Review Amber,Melbourne Genomics Health Alliance Deafness Flagship,Victorian Clinical Genetics Services
Mode of inheritance for gene: ELMOD3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ELMOD3 were set to 31628468; 30284680; 24039609; 29713870
Phenotypes for gene: ELMOD3 were set to Deafness, autosomal dominant; Deafness, autosomal recessive 88, MIM# 615429
Deafness_Isolated v0.0 DIAPH3 Zornitza Stark gene: DIAPH3 was added
gene: DIAPH3 was added to DeafnessIsolated. Sources: Expert Review Amber,Melbourne Genomics Health Alliance Deafness Flagship,Victorian Clinical Genetics Services
Mode of inheritance for gene: DIAPH3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DIAPH3 were set to 20624953; 23441200; 27658576
Phenotypes for gene: DIAPH3 were set to Auditory neuropathy, autosomal dominant, 1, MIM#609129
Deafness_Isolated v0.0 DIABLO Zornitza Stark gene: DIABLO was added
gene: DIABLO was added to DeafnessIsolated. Sources: Expert Review Amber,Melbourne Genomics Health Alliance Deafness Flagship,Victorian Clinical Genetics Services
Mode of inheritance for gene: DIABLO was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DIABLO were set to 10929711; 21722859; 26969326
Phenotypes for gene: DIABLO were set to Deafness, autosomal dominant 64, MIM# 614152
Deafness_Isolated v0.0 CRYM Zornitza Stark gene: CRYM was added
gene: CRYM was added to DeafnessIsolated. Sources: Expert Review Amber,Melbourne Genomics Health Alliance Deafness Flagship,Victorian Clinical Genetics Services
Mode of inheritance for gene: CRYM was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CRYM were set to 16740909; 24676347; 18448257; 26915689; 12471561
Phenotypes for gene: CRYM were set to Deafness, autosomal dominant 40, MIM# 616357
Deafness_Isolated v0.0 CLIC5 Zornitza Stark gene: CLIC5 was added
gene: CLIC5 was added to DeafnessIsolated. Sources: Expert Review Amber,Melbourne Genomics Health Alliance Deafness Flagship,Victorian Clinical Genetics Services
Mode of inheritance for gene: CLIC5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLIC5 were set to 24781754; 17021174
Phenotypes for gene: CLIC5 were set to Deafness, autosomal recessive 103, MIM# 616042
Deafness_Isolated v0.0 CLDN9 Zornitza Stark gene: CLDN9 was added
gene: CLDN9 was added to DeafnessIsolated. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: CLDN9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLDN9 were set to 31175426; 19696885
Phenotypes for gene: CLDN9 were set to Deafness, autosomal recessive
Deafness_Isolated v0.0 CACNA1D Zornitza Stark gene: CACNA1D was added
gene: CACNA1D was added to DeafnessIsolated. Sources: Expert Review Amber,Melbourne Genomics Health Alliance Deafness Flagship,Victorian Clinical Genetics Services
Mode of inheritance for gene: CACNA1D was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CACNA1D were set to 21131953; 15357422; 22678062
Phenotypes for gene: CACNA1D were set to Sinoatrial node dysfunction and deafness, MIM# 614896
Deafness_Isolated v0.0 WFS1 Zornitza Stark gene: WFS1 was added
gene: WFS1 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: WFS1 was set to Unknown
Deafness_Isolated v0.0 USH2A Zornitza Stark gene: USH2A was added
gene: USH2A was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: USH2A was set to Unknown
Deafness_Isolated v0.0 USH1G Zornitza Stark gene: USH1G was added
gene: USH1G was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: USH1G was set to Unknown
Deafness_Isolated v0.0 USH1C Zornitza Stark gene: USH1C was added
gene: USH1C was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: USH1C was set to Unknown
Deafness_Isolated v0.0 TUBB4B Zornitza Stark gene: TUBB4B was added
gene: TUBB4B was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TUBB4B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBB4B were set to 29198720
Phenotypes for gene: TUBB4B were set to Leber congenital amaurosis with early-onset deafness
Deafness_Isolated v0.0 TRIOBP Zornitza Stark gene: TRIOBP was added
gene: TRIOBP was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TRIOBP was set to Unknown
Deafness_Isolated v0.0 TPRN Zornitza Stark gene: TPRN was added
gene: TPRN was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TPRN was set to Unknown
Deafness_Isolated v0.0 TMPRSS3 Zornitza Stark gene: TMPRSS3 was added
gene: TMPRSS3 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TMPRSS3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMPRSS3 were set to 21786053; 17551081
Phenotypes for gene: TMPRSS3 were set to Deafness, autosomal recessive 8/10, MIM#601072
Deafness_Isolated v0.0 TMIE Zornitza Stark gene: TMIE was added
gene: TMIE was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TMIE was set to Unknown
Deafness_Isolated v0.0 TMC1 Zornitza Stark gene: TMC1 was added
gene: TMC1 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TMC1 was set to Unknown
Deafness_Isolated v0.0 TIMM8A Zornitza Stark gene: TIMM8A was added
gene: TIMM8A was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TIMM8A was set to Unknown
Deafness_Isolated v0.0 TECTA Zornitza Stark gene: TECTA was added
gene: TECTA was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TECTA was set to Unknown
Deafness_Isolated v0.0 TBC1D24 Zornitza Stark gene: TBC1D24 was added
gene: TBC1D24 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TBC1D24 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TBC1D24 were set to 24387994; 24729539; 24729547; 24291220
Phenotypes for gene: TBC1D24 were set to Deafness, autosomal dominant 65, MIM#616044; DOORS syndrome, MIM#220500; Deafness , autosomal recessive 86, MIM#614617
Deafness_Isolated v0.0 SYNE4 Zornitza Stark gene: SYNE4 was added
gene: SYNE4 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SYNE4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SYNE4 were set to 28958982; 23348741
Phenotypes for gene: SYNE4 were set to Deafness, autosomal recessive 76, MIM# 615540
Deafness_Isolated v0.0 STRC Zornitza Stark gene: STRC was added
gene: STRC was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: STRC was set to Unknown
Deafness_Isolated v0.0 SOX10 Zornitza Stark gene: SOX10 was added
gene: SOX10 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SOX10 was set to Unknown
Deafness_Isolated v0.0 SMPX Zornitza Stark gene: SMPX was added
gene: SMPX was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SMPX was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Deafness_Isolated v0.0 SLITRK6 Zornitza Stark gene: SLITRK6 was added
gene: SLITRK6 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLITRK6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLITRK6 were set to 29551497; 23543054
Phenotypes for gene: SLITRK6 were set to deafness and myopia, MIM#221200
Deafness_Isolated v0.0 SLC26A5 Zornitza Stark gene: SLC26A5 was added
gene: SLC26A5 was added to DeafnessIsolated. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: SLC26A5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC26A5 were set to 26969326; 24164807
Phenotypes for gene: SLC26A5 were set to Deafness, autosomal recessive 61, MIM# 613865
Deafness_Isolated v0.0 SLC26A4 Zornitza Stark gene: SLC26A4 was added
gene: SLC26A4 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC26A4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC26A4 were set to 19204907; 9618167
Phenotypes for gene: SLC26A4 were set to Deafness, autosomal recessive 4, with enlarged vestibular aqueduct, MIM#600791; Pendred syndrome, MIM#274600
Deafness_Isolated v0.0 SIX1 Zornitza Stark gene: SIX1 was added
gene: SIX1 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SIX1 was set to Unknown
Phenotypes for gene: SIX1 were set to Brancio-otic syndrome MIM# 608389
Deafness_Isolated v0.0 SERPINB6 Zornitza Stark gene: SERPINB6 was added
gene: SERPINB6 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SERPINB6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SERPINB6 were set to 25719458; 23669344; 20451170
Phenotypes for gene: SERPINB6 were set to Deafness, autosomal recessive 91, MIM# 613453
Deafness_Isolated v0.0 S1PR2 Zornitza Stark gene: S1PR2 was added
gene: S1PR2 was added to DeafnessIsolated. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: S1PR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: S1PR2 were set to 29776397; 27383011; 26805784
Phenotypes for gene: S1PR2 were set to Deafness, autosomal recessive 68, MIM# 610419
Deafness_Isolated v0.0 RDX Zornitza Stark gene: RDX was added
gene: RDX was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: RDX was set to BIALLELIC, autosomal or pseudoautosomal
Deafness_Isolated v0.0 PTPRQ Zornitza Stark gene: PTPRQ was added
gene: PTPRQ was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: PTPRQ was set to Unknown
Deafness_Isolated v0.0 PRPS1 Zornitza Stark gene: PRPS1 was added
gene: PRPS1 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: PRPS1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Deafness_Isolated v0.0 POU3F4 Zornitza Stark gene: POU3F4 was added
gene: POU3F4 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: POU3F4 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: POU3F4 were set to 31786483; 30176854
Phenotypes for gene: POU3F4 were set to Deafness, X-linked 2, MIM# 304400
Deafness_Isolated v0.0 PLS1 Zornitza Stark gene: PLS1 was added
gene: PLS1 was added to DeafnessIsolated. Sources: Literature,Expert Review Green
Mode of inheritance for gene: PLS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PLS1 were set to 31397523; 31432506; 30872814
Phenotypes for gene: PLS1 were set to Deafness
Deafness_Isolated v0.0 PDZD7 Zornitza Stark gene: PDZD7 was added
gene: PDZD7 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: PDZD7 was set to Unknown
Deafness_Isolated v0.0 PCDH15 Zornitza Stark gene: PCDH15 was added
gene: PCDH15 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: PCDH15 was set to Unknown
Deafness_Isolated v0.0 PAX3 Zornitza Stark gene: PAX3 was added
gene: PAX3 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: PAX3 was set to Unknown
Deafness_Isolated v0.0 OTOGL Zornitza Stark gene: OTOGL was added
gene: OTOGL was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: OTOGL was set to Unknown
Deafness_Isolated v0.0 OTOG Zornitza Stark gene: OTOG was added
gene: OTOG was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: OTOG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OTOG were set to 23122587; 29800624
Phenotypes for gene: OTOG were set to Deafness, autosomal recessive 18B, MIM#614945
Deafness_Isolated v0.0 OTOF Zornitza Stark gene: OTOF was added
gene: OTOF was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: OTOF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OTOF were set to 22906306; 16371502
Phenotypes for gene: OTOF were set to Auditory neuropathy, autosomal recessive, 1 (MIM # 601071); Deafness, autosomal recessive 9 (MIM # 601071
Deafness_Isolated v0.0 OTOA Zornitza Stark gene: OTOA was added
gene: OTOA was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: OTOA was set to Unknown
Deafness_Isolated v0.0 OSBPL2 Zornitza Stark gene: OSBPL2 was added
gene: OSBPL2 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: OSBPL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: OSBPL2 were set to 30894143; 31451425; 25759012; 25077649
Phenotypes for gene: OSBPL2 were set to Deafness, autosomal dominant 67, MIM# 616340
Deafness_Isolated v0.0 MYO7A Zornitza Stark gene: MYO7A was added
gene: MYO7A was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: MYO7A was set to Unknown
Deafness_Isolated v0.0 MYO6 Zornitza Stark gene: MYO6 was added
gene: MYO6 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: MYO6 was set to Unknown
Deafness_Isolated v0.0 MYO15A Zornitza Stark gene: MYO15A was added
gene: MYO15A was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: MYO15A was set to Unknown
Deafness_Isolated v0.0 MYH9 Zornitza Stark gene: MYH9 was added
gene: MYH9 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: MYH9 was set to Unknown
Deafness_Isolated v0.0 MYH14 Zornitza Stark gene: MYH14 was added
gene: MYH14 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: MYH14 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: MYH14 were set to Deafness, autosomal dominant 4A, MIM# 600652
Deafness_Isolated v0.0 MSRB3 Zornitza Stark gene: MSRB3 was added
gene: MSRB3 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: MSRB3 was set to Unknown
Publications for gene: MSRB3 were set to 21185009; 24191262; 19650862
Phenotypes for gene: MSRB3 were set to Deafness, autosomal recessive 74, MIM# 613718
Deafness_Isolated v0.0 MPZL2 Zornitza Stark gene: MPZL2 was added
gene: MPZL2 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: MPZL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MPZL2 were set to 29982980; 29961571
Phenotypes for gene: MPZL2 were set to Deafness, autosomal recessive 111, MIM#618145
Deafness_Isolated v0.0 MITF Zornitza Stark gene: MITF was added
gene: MITF was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: MITF was set to Unknown
Deafness_Isolated v0.0 MARVELD2 Zornitza Stark gene: MARVELD2 was added
gene: MARVELD2 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: MARVELD2 was set to Unknown
Deafness_Isolated v0.0 LRTOMT Zornitza Stark gene: LRTOMT was added
gene: LRTOMT was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: LRTOMT was set to Unknown
Deafness_Isolated v0.0 LOXHD1 Zornitza Stark gene: LOXHD1 was added
gene: LOXHD1 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: LOXHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LOXHD1 were set to 19732867; 25792669
Phenotypes for gene: LOXHD1 were set to Deafness, autosomal recessive 77, MIM# 613079
Deafness_Isolated v0.0 LHFPL5 Zornitza Stark gene: LHFPL5 was added
gene: LHFPL5 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: LHFPL5 was set to Unknown
Deafness_Isolated v0.0 LARS2 Zornitza Stark gene: LARS2 was added
gene: LARS2 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: LARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: LARS2 were set to Perrault syndrome 4, MIM#615300
Deafness_Isolated v0.0 KIT Zornitza Stark gene: KIT was added
gene: KIT was added to DeafnessIsolated. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: KIT was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: KIT were set to Piebaldism, MIM# 172800
Deafness_Isolated v0.0 KCNQ1 Zornitza Stark gene: KCNQ1 was added
gene: KCNQ1 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: KCNQ1 was set to Unknown
Deafness_Isolated v0.0 KCNE1 Zornitza Stark gene: KCNE1 was added
gene: KCNE1 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: KCNE1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: KCNE1 were set to Jervell and Lange-Nielsen syndrome 2, MIM# 612347
Deafness_Isolated v0.0 KARS Zornitza Stark gene: KARS was added
gene: KARS was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: KARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KARS were set to 14975237; 23768514
Phenotypes for gene: KARS were set to Deafness, autosomal recessive 89, MIM# 613916
Deafness_Isolated v0.0 ILDR1 Zornitza Stark gene: ILDR1 was added
gene: ILDR1 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: ILDR1 was set to Unknown
Deafness_Isolated v0.0 HSD17B4 Zornitza Stark gene: HSD17B4 was added
gene: HSD17B4 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: HSD17B4 was set to Unknown
Deafness_Isolated v0.0 HOMER2 Zornitza Stark gene: HOMER2 was added
gene: HOMER2 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: HOMER2 was set to Unknown
Publications for gene: HOMER2 were set to 25816005; 30047143
Phenotypes for gene: HOMER2 were set to Deafness, autosomal dominant 68, MIM# 616707
Deafness_Isolated v0.0 HGF Zornitza Stark gene: HGF was added
gene: HGF was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: HGF was set to Unknown
Publications for gene: HGF were set to 19576567; 27488639
Phenotypes for gene: HGF were set to Deafness, autosomal recessive 39, MIM# 608265
Deafness_Isolated v0.0 HARS2 Zornitza Stark gene: HARS2 was added
gene: HARS2 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: HARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HARS2 were set to 21464306; 27650058; 31486067; 31827252
Phenotypes for gene: HARS2 were set to Perrault syndrome 2, MIM# 614926
Deafness_Isolated v0.0 GRXCR1 Zornitza Stark gene: GRXCR1 was added
gene: GRXCR1 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: GRXCR1 was set to
Deafness_Isolated v0.0 GRHL2 Zornitza Stark gene: GRHL2 was added
gene: GRHL2 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: GRHL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: GRHL2 were set to Deafness, autosomal dominant 28, MIM# 608641
Deafness_Isolated v0.0 GPSM2 Zornitza Stark gene: GPSM2 was added
gene: GPSM2 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: GPSM2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GPSM2 were set to Chudley-McCullough syndrome
Deafness_Isolated v0.0 GJB2 Zornitza Stark gene: GJB2 was added
gene: GJB2 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: GJB2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: GJB2 were set to 9529365; 14985372; 11354642; 19941053
Phenotypes for gene: GJB2 were set to Keratitis-ichthyosis-deafness syndrome, MIM#148210; Deafness, autosomal dominant 3A, MIM#601544; Bart-Pumphrey syndrome, MIM#149200; Vohwinkel syndrome, MIM# 124500; Deafness, autosomal recessive 1A, MIM#220290; Keratoderma, palmoplantar, with deafness, MIM#148350; Hystrix-like ichthyosis with deafness, MIM#602540
Deafness_Isolated v0.0 GIPC3 Zornitza Stark gene: GIPC3 was added
gene: GIPC3 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: GIPC3 was set to Unknown
Deafness_Isolated v0.0 GATA3 Zornitza Stark gene: GATA3 was added
gene: GATA3 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: GATA3 was set to Unknown
Deafness_Isolated v0.0 FOXI1 Zornitza Stark gene: FOXI1 was added
gene: FOXI1 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: FOXI1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FOXI1 were set to 9843211; 29242249; 17503324
Phenotypes for gene: FOXI1 were set to Hearing loss and renal tubular acidosis
Deafness_Isolated v0.0 EYA1 Zornitza Stark gene: EYA1 was added
gene: EYA1 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: EYA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: EYA1 were set to branchiio-oto-renal syndrome
Deafness_Isolated v0.0 ESRRB Zornitza Stark gene: ESRRB was added
gene: ESRRB was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: ESRRB was set to Unknown
Deafness_Isolated v0.0 ESPN Zornitza Stark gene: ESPN was added
gene: ESPN was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: ESPN was set to BIALLELIC, autosomal or pseudoautosomal
Deafness_Isolated v0.0 EPS8L2 Zornitza Stark gene: EPS8L2 was added
gene: EPS8L2 was added to DeafnessIsolated. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: EPS8L2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EPS8L2 were set to 23918390; 28281779; 26282398
Phenotypes for gene: EPS8L2 were set to Deafness autosomal recessive 106, MIM# 617637
Deafness_Isolated v0.0 EPS8 Zornitza Stark gene: EPS8 was added
gene: EPS8 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: EPS8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EPS8 were set to 24741995
Phenotypes for gene: EPS8 were set to Deafness, autosomal recessive 102, MIM# 615974
Deafness_Isolated v0.0 EDNRB Zornitza Stark gene: EDNRB was added
gene: EDNRB was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: EDNRB was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: EDNRB were set to Waardenburg syndrome, type 4A, MIM# 277580
Deafness_Isolated v0.0 EDN3 Zornitza Stark gene: EDN3 was added
gene: EDN3 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: EDN3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: EDN3 were set to 8630502; 19764030; 11303518
Phenotypes for gene: EDN3 were set to Waardenburg syndrome, type 4B, MIM# 613265
Deafness_Isolated v0.0 DMXL2 Zornitza Stark gene: DMXL2 was added
gene: DMXL2 was added to DeafnessIsolated. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: DMXL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DMXL2 were set to 31688942; 27657680; 22875945
Phenotypes for gene: DMXL2 were set to autosomal recessive EE with deafness; Autosomal dominant hearing loss
Deafness_Isolated v0.0 DIAPH1 Zornitza Stark gene: DIAPH1 was added
gene: DIAPH1 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: DIAPH1 was set to Unknown
Deafness_Isolated v0.0 DFNB59 Zornitza Stark gene: DFNB59 was added
gene: DFNB59 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: DFNB59 was set to Unknown
Deafness_Isolated v0.0 DFNA5 Zornitza Stark gene: DFNA5 was added
gene: DFNA5 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: DFNA5 was set to Unknown
Deafness_Isolated v0.0 COL9A3 Zornitza Stark gene: COL9A3 was added
gene: COL9A3 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: COL9A3 was set to Unknown
Deafness_Isolated v0.0 COL9A2 Zornitza Stark gene: COL9A2 was added
gene: COL9A2 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: COL9A2 was set to Unknown
Deafness_Isolated v0.0 COL9A1 Zornitza Stark gene: COL9A1 was added
gene: COL9A1 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: COL9A1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: COL9A1 were set to Stickler syndrome, type IV, MIM#614134
Deafness_Isolated v0.0 COL2A1 Zornitza Stark gene: COL2A1 was added
gene: COL2A1 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: COL2A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COL2A1 were set to 27408751
Phenotypes for gene: COL2A1 were set to Stickler syndrome, type I, MIM108300
Deafness_Isolated v0.0 COL11A2 Zornitza Stark gene: COL11A2 was added
gene: COL11A2 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: COL11A2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: COL11A2 were set to Non syndromic deafness
Deafness_Isolated v0.0 COL11A1 Zornitza Stark gene: COL11A1 was added
gene: COL11A1 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: COL11A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: COL11A1 were set to Stickler syndrome
Deafness_Isolated v0.0 COCH Zornitza Stark gene: COCH was added
gene: COCH was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: COCH was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: COCH were set to Non syndromic deafness
Deafness_Isolated v0.0 CLRN1 Zornitza Stark gene: CLRN1 was added
gene: CLRN1 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CLRN1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CLRN1 were set to Usher syndrome
Deafness_Isolated v0.0 CLPP Zornitza Stark gene: CLPP was added
gene: CLPP was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CLPP was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CLPP were set to Perrault syndrome
Deafness_Isolated v0.0 CLDN14 Zornitza Stark gene: CLDN14 was added
gene: CLDN14 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CLDN14 was set to BIALLELIC, autosomal or pseudoautosomal
Deafness_Isolated v0.0 CIB2 Zornitza Stark gene: CIB2 was added
gene: CIB2 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CIB2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CIB2 were set to Deafness, autosomal recessive 48
Deafness_Isolated v0.0 CHD7 Zornitza Stark gene: CHD7 was added
gene: CHD7 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CHD7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CHD7 were set to CHARGE syndrome
Deafness_Isolated v0.0 CEP78 Zornitza Stark gene: CEP78 was added
gene: CEP78 was added to DeafnessIsolated. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: CEP78 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP78 were set to 27588452; 28005958; 27588451; 27627988
Phenotypes for gene: CEP78 were set to Cone-rod dystrophy and hearing loss, MIM#617236
Deafness_Isolated v0.0 CEACAM16 Zornitza Stark gene: CEACAM16 was added
gene: CEACAM16 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CEACAM16 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: CEACAM16 were set to 25589040; 21368133; 22544735; 31249509; 29703829; 30514912
Phenotypes for gene: CEACAM16 were set to Deafness, autosomal dominant 4B, MIM# 614614; Deafness, autosomal recessive 113, MIM# 618410
Deafness_Isolated v0.0 CDH23 Zornitza Stark gene: CDH23 was added
gene: CDH23 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CDH23 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDH23 were set to 25468891; 11138009; 21940737
Phenotypes for gene: CDH23 were set to Deafness, autosomal recessive 12 (MIM # 601386); Usher syndrome, type 1D/F digenic (MIM #601067); Usher syndrome, type 1D (MIM# 601067)
Deafness_Isolated v0.0 CDC14A Zornitza Stark gene: CDC14A was added
gene: CDC14A was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CDC14A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDC14A were set to 29293958; 27259055
Phenotypes for gene: CDC14A were set to Deafness, autosomal recessive 32, with or without immotile sperm, MIM# 608653
Deafness_Isolated v0.0 CCDC50 Zornitza Stark gene: CCDC50 was added
gene: CCDC50 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CCDC50 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CCDC50 were set to 24875298; 27911912; 17503326
Phenotypes for gene: CCDC50 were set to Deafness, autosomal dominant 44, MIM# 607453; Childhood onset deafness, progressive
Deafness_Isolated v0.0 CABP2 Zornitza Stark gene: CABP2 was added
gene: CABP2 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CABP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CABP2 were set to 22981119; 28183797; 31661684
Phenotypes for gene: CABP2 were set to Deafness, autosomal recessive 93, MIM# 614899
Deafness_Isolated v0.0 BCS1L Zornitza Stark gene: BCS1L was added
gene: BCS1L was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: BCS1L was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: BCS1L were set to Bjornstad syndrome: SNHL and pili torti
Deafness_Isolated v0.0 ATP2B2 Zornitza Stark gene: ATP2B2 was added
gene: ATP2B2 was added to DeafnessIsolated. Sources: Literature,Expert Review Green
Mode of inheritance for gene: ATP2B2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP2B2 were set to 30535804
Phenotypes for gene: ATP2B2 were set to post lingual progressive sensorineural deafness
Deafness_Isolated v0.0 ALMS1 Zornitza Stark gene: ALMS1 was added
gene: ALMS1 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: ALMS1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ALMS1 were set to Alstrom syndrome
Deafness_Isolated v0.0 AIFM1 Zornitza Stark gene: AIFM1 was added
gene: AIFM1 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: AIFM1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: AIFM1 were set to 25986071
Phenotypes for gene: AIFM1 were set to Deafness, X-linked 5, MIM# 300614
Deafness_Isolated v0.0 ADGRV1 Zornitza Stark gene: ADGRV1 was added
gene: ADGRV1 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: ADGRV1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ADGRV1 were set to Usher syndrome
Deafness_Isolated v0.0 ACTG1 Zornitza Stark gene: ACTG1 was added
gene: ACTG1 was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: ACTG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ACTG1 were set to 29620237
Phenotypes for gene: ACTG1 were set to DFNA20 - isolated
Deafness_Isolated v0.0 Zornitza Stark Added panel DeafnessIsolated
Common Variable Immunodeficiency v0.76 Bryony Thompson Panel types changed to Melbourne Genomics; Victorian Clinical Genetics Services; Royal Melbourne Hospital
Common Variable Immunodeficiency v0.75 TRNT1 Bryony Thompson Mode of inheritance for gene: TRNT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Common Variable Immunodeficiency v0.74 TRNT1 Bryony Thompson Classified gene: TRNT1 as Green List (high evidence)
Common Variable Immunodeficiency v0.74 TRNT1 Bryony Thompson Added comment: Comment on list classification: On the IUIS CVID phenotype gene list for human inborn errors of immunity (PMID: 32048120).
Common Variable Immunodeficiency v0.74 TRNT1 Bryony Thompson Gene: trnt1 has been classified as Green List (High Evidence).
Common Variable Immunodeficiency v0.73 TRNT1 Bryony Thompson Phenotypes for gene: TRNT1 were changed from to Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay MIM#616084
Common Variable Immunodeficiency v0.72 TNFSF12 Bryony Thompson reviewed gene: TNFSF12: Rating: AMBER; Mode of pathogenicity: None; Publications: 32048120, 23493554; Phenotypes: Common variable immunodeficiency; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Common Variable Immunodeficiency v0.72 TNFRSF13C Bryony Thompson Classified gene: TNFRSF13C as Amber List (moderate evidence)
Common Variable Immunodeficiency v0.72 TNFRSF13C Bryony Thompson Added comment: Comment on list classification: On the IUIS CVID phenotype gene list for human inborn errors of immunity (PMID: 32048120).
Common Variable Immunodeficiency v0.72 TNFRSF13C Bryony Thompson Gene: tnfrsf13c has been classified as Amber List (Moderate Evidence).
Common Variable Immunodeficiency v0.71 TNFRSF13B Bryony Thompson Classified gene: TNFRSF13B as Green List (high evidence)
Common Variable Immunodeficiency v0.71 TNFRSF13B Bryony Thompson Added comment: Comment on list classification: On the IUIS CVID phenotype gene list for human inborn errors of immunity (PMID: 32048120).
Common Variable Immunodeficiency v0.71 TNFRSF13B Bryony Thompson Gene: tnfrsf13b has been classified as Green List (High Evidence).
Common Variable Immunodeficiency v0.70 SEC61A1 Bryony Thompson Marked gene: SEC61A1 as ready
Common Variable Immunodeficiency v0.70 SEC61A1 Bryony Thompson Gene: sec61a1 has been classified as Amber List (Moderate Evidence).
Common Variable Immunodeficiency v0.70 SEC61A1 Bryony Thompson Classified gene: SEC61A1 as Amber List (moderate evidence)
Common Variable Immunodeficiency v0.70 SEC61A1 Bryony Thompson Gene: sec61a1 has been classified as Amber List (Moderate Evidence).
Common Variable Immunodeficiency v0.69 SEC61A1 Bryony Thompson edited their review of gene: SEC61A1: Changed publications: 28782633, 32048120
Common Variable Immunodeficiency v0.69 SEC61A1 Bryony Thompson changed review comment from: Two unrelated families with a heterozygous missense (p.V85D) and nonsense (p.E381*) segregating with the disease phenotype, and supporting in vitro functional assays.
Sources: Expert list; to: Two unrelated families with a heterozygous missense (p.V85D) and nonsense (p.E381*) segregating with the disease phenotype, and supporting in vitro functional assays.
On the IUIS CVID phenotype gene list for human inborn errors of immunity (PMID: 32048120).
Sources: Expert list
Common Variable Immunodeficiency v0.69 SEC61A1 Bryony Thompson gene: SEC61A1 was added
gene: SEC61A1 was added to Common Variable Immunodeficiency. Sources: Expert list
Mode of inheritance for gene: SEC61A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SEC61A1 were set to 28782633
Phenotypes for gene: SEC61A1 were set to hypogammaglobulinemia; common variable immunodeficiency
Review for gene: SEC61A1 was set to AMBER
Added comment: Two unrelated families with a heterozygous missense (p.V85D) and nonsense (p.E381*) segregating with the disease phenotype, and supporting in vitro functional assays.
Sources: Expert list
Common Variable Immunodeficiency v0.68 PTEN Bryony Thompson Marked gene: PTEN as ready
Common Variable Immunodeficiency v0.68 PTEN Bryony Thompson Gene: pten has been classified as Green List (High Evidence).
Common Variable Immunodeficiency v0.68 PTEN Bryony Thompson Classified gene: PTEN as Green List (high evidence)
Common Variable Immunodeficiency v0.68 PTEN Bryony Thompson Gene: pten has been classified as Green List (High Evidence).
Common Variable Immunodeficiency v0.67 PTEN Bryony Thompson gene: PTEN was added
gene: PTEN was added to Common Variable Immunodeficiency. Sources: Expert list
Mode of inheritance for gene: PTEN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTEN were set to 27531073; 27426521
Phenotypes for gene: PTEN were set to Macrocephaly/autism syndrome MIM#605309; Cowden syndrome 1 MIM#158350
Review for gene: PTEN was set to GREEN
Added comment: At least 4 unrelated probands with PTEN loss of function variants have been reported with hypogammaglobulinemia, fulfilling the common variable immunodeficiency (CVID) disorders diagnostic criteria.
On the IUIS CVID phenotype gene list for human inborn errors of immunity (PMID: 32048120).
Sources: Expert list
Common Variable Immunodeficiency v0.66 RAC2 Bryony Thompson Marked gene: RAC2 as ready
Common Variable Immunodeficiency v0.66 RAC2 Bryony Thompson Gene: rac2 has been classified as Amber List (Moderate Evidence).
Common Variable Immunodeficiency v0.66 RAC2 Bryony Thompson Classified gene: RAC2 as Amber List (moderate evidence)
Common Variable Immunodeficiency v0.66 RAC2 Bryony Thompson Gene: rac2 has been classified as Amber List (Moderate Evidence).
Common Variable Immunodeficiency v0.65 RAC2 Bryony Thompson gene: RAC2 was added
gene: RAC2 was added to Common Variable Immunodeficiency. Sources: Expert list
Mode of inheritance for gene: RAC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAC2 were set to 25512081; 32048120; 14564011
Phenotypes for gene: RAC2 were set to Common variable immunodeficiency
Review for gene: RAC2 was set to AMBER
Added comment: Two siblings homozygous for a loss of function variant and a phenotype resembling CVID (not in OMIM), with supporting immunological assays of patient cells. Null mouse model demonstrates the gene has a critical role in B cell development and signalling. On the IUIS CVID phenotype gene list for human inborn errors of immunity (PMID: 32048120).
Sources: Expert list
Common Variable Immunodeficiency v0.64 PIK3R1 Bryony Thompson Marked gene: PIK3R1 as ready
Common Variable Immunodeficiency v0.64 PIK3R1 Bryony Thompson Gene: pik3r1 has been classified as Green List (High Evidence).
Common Variable Immunodeficiency v0.64 PIK3R1 Bryony Thompson Classified gene: PIK3R1 as Green List (high evidence)
Common Variable Immunodeficiency v0.64 PIK3R1 Bryony Thompson Gene: pik3r1 has been classified as Green List (High Evidence).
Polydactyly v0.36 ALX3 Anand Vasudevan reviewed gene: ALX3: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 ALMS1 Anand Vasudevan reviewed gene: ALMS1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Common Variable Immunodeficiency v0.63 PIK3R1 Bryony Thompson gene: PIK3R1 was added
gene: PIK3R1 was added to Common Variable Immunodeficiency. Sources: Expert list
Mode of inheritance for gene: PIK3R1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PIK3R1 were set to 32048120; 27076228
Phenotypes for gene: PIK3R1 were set to Immunodeficiency 36 MIM#616005
Review for gene: PIK3R1 was set to GREEN
Added comment: 36 cases with PIK3R1-associated immunodeficiency were detected with c.1425+1G>A (42%), c.1425+1G>C (29%), c.1425+1G>T (13%). Four additional cases had mutations involving c.1425+2, and another had a G-C substitution at the -1 position of the splice acceptor site of exon 11. Analysis of patient mRNA demonstrated that all of the variants cause skipping of exon 11 (coding exon 10).
On the IUIS CVID phenotype gene list for human inborn errors of immunity (PMID: 32048120).
Sources: Expert list
Polydactyly v0.36 PDE6D Anand Vasudevan reviewed gene: PDE6D: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 CD96 Anand Vasudevan reviewed gene: CD96: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.36 ZSWIM6 Anand Vasudevan reviewed gene: ZSWIM6: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.36 ZNF141 Anand Vasudevan reviewed gene: ZNF141: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 WNT7A Anand Vasudevan reviewed gene: WNT7A: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 WDR60 Anand Vasudevan reviewed gene: WDR60: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 WDR35 Anand Vasudevan reviewed gene: WDR35: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 WDR34 Anand Vasudevan reviewed gene: WDR34: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 WDR19 Anand Vasudevan reviewed gene: WDR19: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 WDPCP Anand Vasudevan reviewed gene: WDPCP: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 USP9X Anand Vasudevan reviewed gene: USP9X: 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)
Polydactyly v0.36 UBE3B Anand Vasudevan reviewed gene: UBE3B: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 TWIST1 Anand Vasudevan reviewed gene: TWIST1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.36 TTC8 Anand Vasudevan reviewed gene: TTC8: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 TTC21B Anand Vasudevan reviewed gene: TTC21B: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Polydactyly v0.36 TRAF3IP1 Anand Vasudevan reviewed gene: TRAF3IP1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 TMEM67 Anand Vasudevan reviewed gene: TMEM67: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 TMEM237 Anand Vasudevan reviewed gene: TMEM237: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 TMEM231 Anand Vasudevan reviewed gene: TMEM231: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 TMEM216 Anand Vasudevan reviewed gene: TMEM216: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 TMEM138 Anand Vasudevan reviewed gene: TMEM138: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 TFAP2B Anand Vasudevan reviewed gene: TFAP2B: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.36 TFAP2A Anand Vasudevan reviewed gene: TFAP2A: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.36 TCTN3 Anand Vasudevan reviewed gene: TCTN3: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 TCTN2 Anand Vasudevan reviewed gene: TCTN2: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 TCTEX1D2 Anand Vasudevan reviewed gene: TCTEX1D2: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 TBX5 Anand Vasudevan reviewed gene: TBX5: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.36 TBX3 Anand Vasudevan reviewed gene: TBX3: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.36 TBX22 Anand Vasudevan reviewed gene: TBX22: 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)
Polydactyly v0.36 SPINT2 Anand Vasudevan reviewed gene: SPINT2: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 SMOC1 Anand Vasudevan reviewed gene: SMOC1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 SMO Anand Vasudevan edited their review of gene: SMO: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Polydactyly v0.36 SMO Anand Vasudevan reviewed gene: SMO: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 SHH Anand Vasudevan reviewed gene: SHH: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.36 SDCCAG8 Anand Vasudevan reviewed gene: SDCCAG8: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 SC5D Anand Vasudevan reviewed gene: SC5D: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 SALL4 Anand Vasudevan reviewed gene: SALL4: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.36 SALL1 Anand Vasudevan reviewed gene: SALL1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.36 RPGRIP1L Anand Vasudevan reviewed gene: RPGRIP1L: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 RBM10 Anand Vasudevan reviewed gene: RBM10: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 RAB23 Anand Vasudevan reviewed gene: RAB23: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 PROM1 Anand Vasudevan reviewed gene: PROM1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Polydactyly v0.36 PORCN Anand Vasudevan reviewed gene: PORCN: 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)
Polydactyly v0.36 PNPLA6 Anand Vasudevan reviewed gene: PNPLA6: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 PITX1 Anand Vasudevan reviewed gene: PITX1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.36 PIK3R2 Anand Vasudevan reviewed gene: PIK3R2: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.36 PIK3CA Anand Vasudevan reviewed gene: PIK3CA: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: Other
Polydactyly v0.36 OFD1 Anand Vasudevan reviewed gene: OFD1: 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)
Polydactyly v0.36 NPHP3 Anand Vasudevan reviewed gene: NPHP3: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 NEK1 Anand Vasudevan reviewed gene: NEK1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.36 MKS1 Anand Vasudevan reviewed gene: MKS1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 MKKS Anand Vasudevan reviewed gene: MKKS: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 MEGF8 Anand Vasudevan reviewed gene: MEGF8: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 MBTPS2 Anand Vasudevan reviewed gene: MBTPS2: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Polydactyly v0.36 LZTFL1 Anand Vasudevan reviewed gene: LZTFL1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 LRP4 Anand Vasudevan reviewed gene: LRP4: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Polydactyly v0.36 LMBR1 Anand Vasudevan reviewed gene: LMBR1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Polydactyly v0.36 LBR Anand Vasudevan reviewed gene: LBR: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Polydactyly v0.36 KIF7 Anand Vasudevan reviewed gene: KIF7: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 KIAA0586 Anand Vasudevan reviewed gene: KIAA0586: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 IQCE Anand Vasudevan reviewed gene: IQCE: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 INPP5E Anand Vasudevan reviewed gene: INPP5E: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 IFT80 Anand Vasudevan reviewed gene: IFT80: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 IFT52 Anand Vasudevan reviewed gene: IFT52: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 IFT43 Anand Vasudevan reviewed gene: IFT43: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 IFT27 Anand Vasudevan reviewed gene: IFT27: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 IFT172 Anand Vasudevan reviewed gene: IFT172: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 IFT140 Anand Vasudevan reviewed gene: IFT140: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 ICK Anand Vasudevan reviewed gene: ICK: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Polydactyly v0.36 HYLS1 Anand Vasudevan reviewed gene: HYLS1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 HOXA13 Anand Vasudevan reviewed gene: HOXA13: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.36 HNRNPK Anand Vasudevan reviewed gene: HNRNPK: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.36 GRIP1 Anand Vasudevan reviewed gene: GRIP1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 GPC3 Anand Vasudevan reviewed gene: GPC3: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Polydactyly v0.36 GLI3 Anand Vasudevan reviewed gene: GLI3: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.36 GLI2 Anand Vasudevan reviewed gene: GLI2: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.36 GDF5 Anand Vasudevan reviewed gene: GDF5: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Polydactyly v0.36 FREM2 Anand Vasudevan reviewed gene: FREM2: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 FRAS1 Anand Vasudevan reviewed gene: FRAS1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 FGFR3 Anand Vasudevan reviewed gene: FGFR3: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.36 FGFR2 Anand Vasudevan reviewed gene: FGFR2: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.36 FGFR1 Anand Vasudevan reviewed gene: FGFR1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.36 FGF10 Anand Vasudevan reviewed gene: FGF10: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.36 EVC2 Anand Vasudevan reviewed gene: EVC2: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Polydactyly v0.36 EVC Anand Vasudevan reviewed gene: EVC: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Polydactyly v0.36 EBP Anand Vasudevan reviewed gene: EBP: 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)
Polydactyly v0.36 DYNC2LI1 Anand Vasudevan reviewed gene: DYNC2LI1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 DYNC2H1 Anand Vasudevan reviewed gene: DYNC2H1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 DDX59 Anand Vasudevan reviewed gene: DDX59: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 CSPP1 Anand Vasudevan reviewed gene: CSPP1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 CKAP2L Anand Vasudevan reviewed gene: CKAP2L: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 CEP41 Anand Vasudevan reviewed gene: CEP41: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 CEP290 Anand Vasudevan reviewed gene: CEP290: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 CEP164 Anand Vasudevan reviewed gene: CEP164: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 CEP120 Anand Vasudevan reviewed gene: CEP120: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 CENPF Anand Vasudevan reviewed gene: CENPF: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 CCND2 Anand Vasudevan reviewed gene: CCND2: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.36 CC2D2A Anand Vasudevan reviewed gene: CC2D2A: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 C5orf42 Anand Vasudevan reviewed gene: C5orf42: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 C2CD3 Anand Vasudevan reviewed gene: C2CD3: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 BMP4 Anand Vasudevan reviewed gene: BMP4: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.36 BHLHA9 Anand Vasudevan reviewed gene: BHLHA9: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 BBS9 Anand Vasudevan reviewed gene: BBS9: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 BBS7 Anand Vasudevan reviewed gene: BBS7: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 BBS5 Anand Vasudevan reviewed gene: BBS5: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 BBS4 Anand Vasudevan reviewed gene: BBS4: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 BBS2 Anand Vasudevan reviewed gene: BBS2: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 BBS12 Anand Vasudevan reviewed gene: BBS12: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 BBS10 Anand Vasudevan reviewed gene: BBS10: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 BBS1 Anand Vasudevan reviewed gene: BBS1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 B9D2 Anand Vasudevan reviewed gene: B9D2: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 ARL6 Anand Vasudevan reviewed gene: ARL6: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.36 AKT3 Anand Vasudevan reviewed gene: AKT3: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.36 AHI1 Anand Vasudevan reviewed gene: AHI1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Common Variable Immunodeficiency v0.62 PIK3CD Bryony Thompson Added comment: Comment on mode of pathogenicity: Gain of function is the mechanism of disease (PMID: 30018075)
Common Variable Immunodeficiency v0.62 PIK3CD Bryony Thompson Mode of pathogenicity for gene: PIK3CD 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
Common Variable Immunodeficiency v0.61 PIK3CD Bryony Thompson Phenotypes for gene: PIK3CD were changed from to Immunodeficiency 14 MIM#615513
Common Variable Immunodeficiency v0.60 PIK3CD Bryony Thompson Mode of inheritance for gene: PIK3CD was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Common Variable Immunodeficiency v0.59 PIK3CD Bryony Thompson Classified gene: PIK3CD as Green List (high evidence)
Common Variable Immunodeficiency v0.59 PIK3CD Bryony Thompson Added comment: Comment on list classification: On the IUIS CVID phenotype gene list for human inborn errors of immunity (PMID: 32048120).
Common Variable Immunodeficiency v0.59 PIK3CD Bryony Thompson Gene: pik3cd has been classified as Green List (High Evidence).
Common Variable Immunodeficiency v0.58 NFKB2 Bryony Thompson Phenotypes for gene: NFKB2 were changed from to Immunodeficiency, common variable, 10 MIM#615577
Common Variable Immunodeficiency v0.57 NFKB2 Bryony Thompson Mode of inheritance for gene: NFKB2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Common Variable Immunodeficiency v0.56 NFKB2 Bryony Thompson Classified gene: NFKB2 as Green List (high evidence)
Common Variable Immunodeficiency v0.56 NFKB2 Bryony Thompson Added comment: Comment on list classification: On the IUIS CVID phenotype gene list for human inborn errors of immunity (PMID: 32048120).
Common Variable Immunodeficiency v0.56 NFKB2 Bryony Thompson Gene: nfkb2 has been classified as Green List (High Evidence).
Common Variable Immunodeficiency v0.55 NFKB1 Bryony Thompson Phenotypes for gene: NFKB1 were changed from to Immunodeficiency, common variable, 12 MIM#616576
Common Variable Immunodeficiency v0.54 NFKB1 Bryony Thompson Mode of inheritance for gene: NFKB1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Common Variable Immunodeficiency v0.53 NFKB1 Bryony Thompson Classified gene: NFKB1 as Green List (high evidence)
Common Variable Immunodeficiency v0.53 NFKB1 Bryony Thompson Added comment: Comment on list classification: On the IUIS CVID phenotype gene list for human inborn errors of immunity (PMID: 32048120).
Common Variable Immunodeficiency v0.53 NFKB1 Bryony Thompson Gene: nfkb1 has been classified as Green List (High Evidence).
Common Variable Immunodeficiency v0.52 MOGS Bryony Thompson Marked gene: MOGS as ready
Common Variable Immunodeficiency v0.52 MOGS Bryony Thompson Gene: mogs has been classified as Green List (High Evidence).
Common Variable Immunodeficiency v0.52 MOGS Bryony Thompson Classified gene: MOGS as Green List (high evidence)
Common Variable Immunodeficiency v0.52 MOGS Bryony Thompson Gene: mogs has been classified as Green List (High Evidence).
Common Variable Immunodeficiency v0.51 MOGS Bryony Thompson gene: MOGS was added
gene: MOGS was added to Common Variable Immunodeficiency. Sources: Expert list
Mode of inheritance for gene: MOGS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MOGS were set to 32048120; 10788335; 24716661; 29235540
Phenotypes for gene: MOGS were set to Congenital disorder of glycosylation, type IIb MIM#606056; Mannosyl-oligosaccharide glucosidase deficiency (MOGS)
Review for gene: MOGS was set to GREEN
Added comment: 4 cases in 3 unrelated families with immunodeficiency as a prominent feature of the condition. Analysis of patient cells suggest a loss of function mechanism. On the IUIS CVID phenotype gene list for human inborn errors of immunity (PMID: 32048120).
Sources: Expert list
Common Variable Immunodeficiency v0.50 IRF2BP2 Bryony Thompson Marked gene: IRF2BP2 as ready
Common Variable Immunodeficiency v0.50 IRF2BP2 Bryony Thompson Gene: irf2bp2 has been classified as Amber List (Moderate Evidence).
Common Variable Immunodeficiency v0.50 IRF2BP2 Bryony Thompson Classified gene: IRF2BP2 as Amber List (moderate evidence)
Common Variable Immunodeficiency v0.50 IRF2BP2 Bryony Thompson Gene: irf2bp2 has been classified as Amber List (Moderate Evidence).
Common Variable Immunodeficiency v0.49 IRF2BP2 Bryony Thompson gene: IRF2BP2 was added
gene: IRF2BP2 was added to Common Variable Immunodeficiency. Sources: Expert list
Mode of inheritance for gene: IRF2BP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IRF2BP2 were set to 27016798; 32048120
Phenotypes for gene: IRF2BP2 were set to Immunodeficiency, common variable, 14 MIM#617765
Review for gene: IRF2BP2 was set to AMBER
Added comment: A single family with 3 affected members with a heterozygous missense variant and supporting in vitro assays and assays of patient cells.
On the IUIS CVID phenotype gene list for human inborn errors of immunity (PMID: 32048120).
Sources: Expert list
Common Variable Immunodeficiency v0.48 CD19 Bryony Thompson Phenotypes for gene: CD19 were changed from to Immunodeficiency, common variable, 3 MIM#613493
Common Variable Immunodeficiency v0.47 CD19 Bryony Thompson Mode of inheritance for gene: CD19 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Common Variable Immunodeficiency v0.46 IKZF1 Bryony Thompson Mode of inheritance for gene: IKZF1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Common Variable Immunodeficiency v0.45 IKZF1 Bryony Thompson Phenotypes for gene: IKZF1 were changed from to Immunodeficiency, common variable, 13 MIM#616873
Common Variable Immunodeficiency v0.44 IKZF1 Bryony Thompson Classified gene: IKZF1 as Green List (high evidence)
Common Variable Immunodeficiency v0.44 IKZF1 Bryony Thompson Added comment: Comment on list classification: On the IUIS CVID phenotype gene list for human inborn errors of immunity (PMID: 32048120).
Common Variable Immunodeficiency v0.44 IKZF1 Bryony Thompson Gene: ikzf1 has been classified as Green List (High Evidence).
Common Variable Immunodeficiency v0.43 CD81 Bryony Thompson Classified gene: CD81 as Amber List (moderate evidence)
Common Variable Immunodeficiency v0.43 CD81 Bryony Thompson Added comment: Comment on list classification: On the IUIS CVID phenotype gene list for human inborn errors of immunity (PMID: 32048120).
Common Variable Immunodeficiency v0.43 CD81 Bryony Thompson Gene: cd81 has been classified as Amber List (Moderate Evidence).
Common Variable Immunodeficiency v0.42 MS4A1 Bryony Thompson Classified gene: MS4A1 as Amber List (moderate evidence)
Common Variable Immunodeficiency v0.42 MS4A1 Bryony Thompson Gene: ms4a1 has been classified as Amber List (Moderate Evidence).
Common Variable Immunodeficiency v0.41 MS4A1 Bryony Thompson reviewed gene: MS4A1: Rating: AMBER; Mode of pathogenicity: None; Publications: 20038800, 23966626, 32048120; Phenotypes: Immunodeficiency, common variable, 5 MIM#613495; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Common Variable Immunodeficiency v0.41 MS4A1 Bryony Thompson Deleted their review
Common Variable Immunodeficiency v0.41 MS4A1 Bryony Thompson Deleted their comment
Common Variable Immunodeficiency v0.41 MS4A1 Bryony Thompson Classified gene: MS4A1 as Red List (low evidence)
Common Variable Immunodeficiency v0.41 MS4A1 Bryony Thompson Added comment: Comment on list classification: On the IUIS CVID phenotype gene list for human inborn errors of immunity (PMID: 32048120).
Common Variable Immunodeficiency v0.41 MS4A1 Bryony Thompson Gene: ms4a1 has been classified as Red List (Low Evidence).
Paroxysmal Dyskinesia v0.30 CLCN1 Zornitza Stark Marked gene: CLCN1 as ready
Paroxysmal Dyskinesia v0.30 CLCN1 Zornitza Stark Gene: clcn1 has been classified as Green List (High Evidence).
Paroxysmal Dyskinesia v0.30 CLCN1 Zornitza Stark Phenotypes for gene: CLCN1 were changed from to Myotonia congenita, dominant, MIM# 160800; Myotonia congenita, recessive, MIM# 255700
Common Variable Immunodeficiency v0.40 CD19 Bryony Thompson Classified gene: CD19 as Green List (high evidence)
Common Variable Immunodeficiency v0.40 CD19 Bryony Thompson Added comment: Comment on list classification: On the IUIS CVID phenotype gene list for human inborn errors of immunity (PMID: 32048120).
Common Variable Immunodeficiency v0.40 CD19 Bryony Thompson Gene: cd19 has been classified as Green List (High Evidence).
Common Variable Immunodeficiency v0.39 ATP6AP1 Bryony Thompson Classified gene: ATP6AP1 as Green List (high evidence)
Common Variable Immunodeficiency v0.39 ATP6AP1 Bryony Thompson Added comment: Comment on list classification: On the IUIS CVID phenotype gene list for human inborn errors of immunity (PMID: 32048120).
Common Variable Immunodeficiency v0.39 ATP6AP1 Bryony Thompson Gene: atp6ap1 has been classified as Green List (High Evidence).
Common Variable Immunodeficiency v0.38 ARHGEF1 Bryony Thompson Classified gene: ARHGEF1 as Amber List (moderate evidence)
Common Variable Immunodeficiency v0.38 ARHGEF1 Bryony Thompson Added comment: Comment on list classification: On the IUIS CVID phenotype gene list for human inborn errors of immunity (PMID: 32048120).
Common Variable Immunodeficiency v0.38 ARHGEF1 Bryony Thompson Gene: arhgef1 has been classified as Amber List (Moderate Evidence).
Common Variable Immunodeficiency v0.37 CR2 Bryony Thompson Classified gene: CR2 as Amber List (moderate evidence)
Common Variable Immunodeficiency v0.37 CR2 Bryony Thompson Added comment: Comment on list classification: On the IUIS CVID phenotype gene list for human inborn errors of immunity (PMID: 32048120).
Common Variable Immunodeficiency v0.37 CR2 Bryony Thompson Gene: cr2 has been classified as Amber List (Moderate Evidence).
Common Variable Immunodeficiency v0.36 ARHGEF1 Bryony Thompson Marked gene: ARHGEF1 as ready
Common Variable Immunodeficiency v0.36 ARHGEF1 Bryony Thompson Gene: arhgef1 has been classified as Amber List (Moderate Evidence).
Common Variable Immunodeficiency v0.36 ARHGEF1 Bryony Thompson Classified gene: ARHGEF1 as Amber List (moderate evidence)
Common Variable Immunodeficiency v0.36 ARHGEF1 Bryony Thompson Gene: arhgef1 has been classified as Amber List (Moderate Evidence).
Common Variable Immunodeficiency v0.35 ARHGEF1 Bryony Thompson edited their review of gene: ARHGEF1: Changed phenotypes: Immunodeficiency 62 MIM#618459, ARHGEF1 deficiency
Common Variable Immunodeficiency v0.35 ARHGEF1 Bryony Thompson gene: ARHGEF1 was added
gene: ARHGEF1 was added to Common Variable Immunodeficiency. Sources: Expert list
Mode of inheritance for gene: ARHGEF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARHGEF1 were set to 32048120; 30521495; 16286020
Review for gene: ARHGEF1 was set to AMBER
Added comment: Two siblings in a single family reported with compound heterozygous loss of function variants, with supporting assays in patient cells and in vitro. A null mouse model also demonstrates immunodeficiency. On the IUIS CVID phenotype gene list for human inborn errors of immunity.
Sources: Expert list
Paroxysmal Dyskinesia v0.29 CLCN1 Sue White Classified gene: CLCN1 as Green List (high evidence)
Paroxysmal Dyskinesia v0.29 CLCN1 Sue White Gene: clcn1 has been classified as Green List (High Evidence).
Paroxysmal Dyskinesia v0.28 CLCN1 Sue White gene: CLCN1 was added
gene: CLCN1 was added to Paroxysmal Dyskinesia. Sources: Expert Review
Mode of inheritance for gene: CLCN1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Added comment: Mono- and biallelic variants cause mytonia congenita, which is an important differential diagnosis to other movement disorder presentations
Sources: Expert Review
Genetic Epilepsy v0.759 NSDHL Zornitza Stark Marked gene: NSDHL as ready
Genetic Epilepsy v0.759 NSDHL Zornitza Stark Gene: nsdhl has been classified as Green List (High Evidence).
Genetic Epilepsy v0.759 NSDHL Zornitza Stark Phenotypes for gene: NSDHL were changed from to CK syndrome (MIM#300831)
Genetic Epilepsy v0.758 NSDHL Zornitza Stark Publications for gene: NSDHL were set to
Genetic Epilepsy v0.757 NSDHL Zornitza Stark Mode of inheritance for gene: NSDHL was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.2779 NSDHL Zornitza Stark Marked gene: NSDHL as ready
Intellectual disability syndromic and non-syndromic v0.2779 NSDHL Zornitza Stark Gene: nsdhl has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2779 NSDHL Zornitza Stark Phenotypes for gene: NSDHL were changed from to CK syndrome (MIM#300831)
Intellectual disability syndromic and non-syndromic v0.2778 NSDHL Zornitza Stark Publications for gene: NSDHL were set to
Intellectual disability syndromic and non-syndromic v0.2777 NSDHL Zornitza Stark Mode of inheritance for gene: NSDHL was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.3433 NR0B1 Zornitza Stark Marked gene: NR0B1 as ready
Mendeliome v0.3433 NR0B1 Zornitza Stark Added comment: Comment when marking as ready: Note 46XY reversal disorder is only associated with duplications.
Mendeliome v0.3433 NR0B1 Zornitza Stark Gene: nr0b1 has been classified as Green List (High Evidence).
Mendeliome v0.3433 NR0B1 Zornitza Stark Phenotypes for gene: NR0B1 were changed from Adrenal hypoplasia, congenital (MIM# 300200) to Adrenal hypoplasia, congenital (MIM# 300200); 46XY sex reversal 2, dosage-sensitive, MIM# 300018
Mendeliome v0.3432 NR0B1 Zornitza Stark Classified gene: NR0B1 as Green List (high evidence)
Mendeliome v0.3432 NR0B1 Zornitza Stark Gene: nr0b1 has been classified as Green List (High Evidence).
Mendeliome v0.3431 NR0B1 Zornitza Stark Classified gene: NR0B1 as Amber List (moderate evidence)
Mendeliome v0.3431 NR0B1 Zornitza Stark Gene: nr0b1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3430 NR0B1 Zornitza Stark Tag SV/CNV tag was added to gene: NR0B1.
Mendeliome v0.3430 NR0B1 Zornitza Stark Marked gene: NR0B1 as ready
Mendeliome v0.3430 NR0B1 Zornitza Stark Gene: nr0b1 has been classified as Green List (High Evidence).
Mendeliome v0.3430 NR0B1 Zornitza Stark Phenotypes for gene: NR0B1 were changed from to Adrenal hypoplasia, congenital (MIM# 300200)
Mendeliome v0.3429 NR0B1 Zornitza Stark Publications for gene: NR0B1 were set to
Mendeliome v0.3428 NR0B1 Zornitza Stark Mode of inheritance for gene: NR0B1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.3427 NSDHL Zornitza Stark Marked gene: NSDHL as ready
Mendeliome v0.3427 NSDHL Zornitza Stark Gene: nsdhl has been classified as Green List (High Evidence).
Mendeliome v0.3427 NSDHL Zornitza Stark Phenotypes for gene: NSDHL were changed from to CHILD syndrome (MMIM#308050)
Mendeliome v0.3426 NSDHL Zornitza Stark Publications for gene: NSDHL were set to
Mendeliome v0.3425 NSDHL Zornitza Stark Mode of inheritance for gene: NSDHL was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cholestasis v0.30 TFR2 Zornitza Stark Marked gene: TFR2 as ready
Cholestasis v0.30 TFR2 Zornitza Stark Gene: tfr2 has been classified as Green List (High Evidence).
Cholestasis v0.30 TFR2 Zornitza Stark Phenotypes for gene: TFR2 were changed from to Haemochromatosis, type 3 (MIM#604250)
Cholestasis v0.29 TFR2 Zornitza Stark Publications for gene: TFR2 were set to
Cholestasis v0.28 TFR2 Zornitza Stark Mode of inheritance for gene: TFR2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.27 TFR2 Zornitza Stark reviewed gene: TFR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24847265, 29743178; Phenotypes: Haemochromatosis, type 3 (MIM#604250); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3424 TFR2 Zornitza Stark Mode of inheritance for gene: TFR2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3423 TFR2 Zornitza Stark Marked gene: TFR2 as ready
Mendeliome v0.3423 TFR2 Zornitza Stark Gene: tfr2 has been classified as Green List (High Evidence).
Mendeliome v0.3423 TFR2 Zornitza Stark Phenotypes for gene: TFR2 were changed from Hemochromatosis, type 3 (MIM#604250) to Haemochromatosis, type 3 (MIM#604250)
Mendeliome v0.3422 TFR2 Zornitza Stark Phenotypes for gene: TFR2 were changed from to Hemochromatosis, type 3 (MIM#604250)
Mendeliome v0.3421 TFR2 Zornitza Stark Publications for gene: TFR2 were set to
Mendeliome v0.3420 TFR2 Zornitza Stark Mode of inheritance for gene: TFR2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Peroxisomal Disorders v0.15 EBP Zornitza Stark Marked gene: EBP as ready
Peroxisomal Disorders v0.15 EBP Zornitza Stark Added comment: Comment when marking as ready: Enzyme is located primarily in ER, phenotypic overlap with peroxisomal disorders.
Peroxisomal Disorders v0.15 EBP Zornitza Stark Gene: ebp has been classified as Amber List (Moderate Evidence).
Peroxisomal Disorders v0.15 EBP Zornitza Stark Classified gene: EBP as Amber List (moderate evidence)
Peroxisomal Disorders v0.15 EBP Zornitza Stark Gene: ebp has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v0.36 EBP Zornitza Stark Marked gene: EBP as ready
Skeletal dysplasia v0.36 EBP Zornitza Stark Gene: ebp has been classified as Green List (High Evidence).
Skeletal dysplasia v0.36 EBP Zornitza Stark Publications for gene: EBP were set to
Peroxisomal Disorders v0.14 FAR1 Zornitza Stark Marked gene: FAR1 as ready
Peroxisomal Disorders v0.14 FAR1 Zornitza Stark Gene: far1 has been classified as Amber List (Moderate Evidence).
Peroxisomal Disorders v0.14 FAR1 Zornitza Stark Classified gene: FAR1 as Amber List (moderate evidence)
Peroxisomal Disorders v0.14 FAR1 Zornitza Stark Gene: far1 has been classified as Amber List (Moderate Evidence).
Peroxisomal Disorders v0.13 ARSE Zornitza Stark Marked gene: ARSE as ready
Peroxisomal Disorders v0.13 ARSE Zornitza Stark Gene: arse has been classified as Green List (High Evidence).
Peroxisomal Disorders v0.13 ARSE Zornitza Stark Classified gene: ARSE as Green List (high evidence)
Peroxisomal Disorders v0.13 ARSE Zornitza Stark Gene: arse has been classified as Green List (High Evidence).
Peroxisomal Disorders v0.12 Zornitza Stark removed gene:AGK from the panel
Peroxisomal Disorders v0.11 ACBD5 Zornitza Stark Marked gene: ACBD5 as ready
Peroxisomal Disorders v0.11 ACBD5 Zornitza Stark Gene: acbd5 has been classified as Green List (High Evidence).
Peroxisomal Disorders v0.11 ACBD5 Zornitza Stark Phenotypes for gene: ACBD5 were changed from to Retinal dystrophy with leukodystrophy (MIM#618863)
Peroxisomal Disorders v0.10 ACBD5 Zornitza Stark Publications for gene: ACBD5 were set to
Peroxisomal Disorders v0.9 ACBD5 Zornitza Stark Mode of inheritance for gene: ACBD5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3419 ABCD3 Zornitza Stark Marked gene: ABCD3 as ready
Mendeliome v0.3419 ABCD3 Zornitza Stark Gene: abcd3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3419 ABCD3 Zornitza Stark Phenotypes for gene: ABCD3 were changed from to Bile acid synthesis defect, congenital, 5 (MIM#616278)
Mendeliome v0.3418 ABCD3 Zornitza Stark Publications for gene: ABCD3 were set to
Mendeliome v0.3417 ABCD3 Zornitza Stark Mode of inheritance for gene: ABCD3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3416 ABCD3 Zornitza Stark Classified gene: ABCD3 as Amber List (moderate evidence)
Mendeliome v0.3416 ABCD3 Zornitza Stark Gene: abcd3 has been classified as Amber List (Moderate Evidence).
Peroxisomal Disorders v0.8 ABCD3 Zornitza Stark Marked gene: ABCD3 as ready
Peroxisomal Disorders v0.8 ABCD3 Zornitza Stark Gene: abcd3 has been classified as Red List (Low Evidence).
Peroxisomal Disorders v0.8 ABCD3 Zornitza Stark Phenotypes for gene: ABCD3 were changed from to Bile acid synthesis defect, congenital, 5 (MIM#616278)
Peroxisomal Disorders v0.7 ABCD3 Zornitza Stark Publications for gene: ABCD3 were set to
Peroxisomal Disorders v0.6 ABCD3 Zornitza Stark Mode of inheritance for gene: ABCD3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Peroxisomal Disorders v0.5 ABCD3 Zornitza Stark Classified gene: ABCD3 as Red List (low evidence)
Peroxisomal Disorders v0.5 ABCD3 Zornitza Stark Gene: abcd3 has been classified as Red List (Low Evidence).
Pituitary hormone deficiency v0.4 TBC1D32 Zornitza Stark Marked gene: TBC1D32 as ready
Pituitary hormone deficiency v0.4 TBC1D32 Zornitza Stark Gene: tbc1d32 has been classified as Amber List (Moderate Evidence).
Pituitary hormone deficiency v0.4 TBC1D32 Zornitza Stark Classified gene: TBC1D32 as Amber List (moderate evidence)
Pituitary hormone deficiency v0.4 TBC1D32 Zornitza Stark Gene: tbc1d32 has been classified as Amber List (Moderate Evidence).
Pituitary hormone deficiency v0.3 TBC1D32 Zornitza Stark gene: TBC1D32 was added
gene: TBC1D32 was added to Pituitary hormone deficiency. Sources: Literature
Mode of inheritance for gene: TBC1D32 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBC1D32 were set to 32573025; 32060556
Phenotypes for gene: TBC1D32 were set to Syndromic hypopituitarism
Review for gene: TBC1D32 was set to AMBER
Added comment: Two families reported with syndromic hypopituitarism and bi-allelic variants in this gene.
Sources: Literature
Mendeliome v0.3415 TBC1D32 Zornitza Stark Publications for gene: TBC1D32 were set to 24285566
Mendeliome v0.3414 TBC1D32 Zornitza Stark Classified gene: TBC1D32 as Amber List (moderate evidence)
Mendeliome v0.3414 TBC1D32 Zornitza Stark Gene: tbc1d32 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3413 TBC1D32 Zornitza Stark changed review comment from: Three families reported, but phenotypes are broad, some suggestive of ciliopathy.; to: Three families reported now, but phenotypes are broad, some suggestive of ciliopathy.
Mendeliome v0.3413 TBC1D32 Zornitza Stark edited their review of gene: TBC1D32: Added comment: Three families reported, but phenotypes are broad, some suggestive of ciliopathy.; Changed rating: AMBER; Changed publications: 24285566, 32573025, 32060556; Changed phenotypes: Orofaciodigital syndrome type IX, syndromic hypopituitarism
Ciliopathies v0.195 TBC1D32 Zornitza Stark Publications for gene: TBC1D32 were set to 24285566
Ciliopathies v0.194 TBC1D32 Zornitza Stark Classified gene: TBC1D32 as Amber List (moderate evidence)
Ciliopathies v0.194 TBC1D32 Zornitza Stark Gene: tbc1d32 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.756 NSDHL Crystle Lee reviewed gene: NSDHL: Rating: GREEN; Mode of pathogenicity: None; Publications: 21129721, 15689440, 25900314; Phenotypes: CK syndrome (MIM#300831); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.2776 NSDHL Crystle Lee reviewed gene: NSDHL: Rating: GREEN; Mode of pathogenicity: None; Publications: 21129721, 15689440, 25900314; Phenotypes: CK syndrome (MIM#300831); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.3413 NR0B1 Ain Roesley reviewed gene: NR0B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19508677, 26030781; Phenotypes: Adrenal hypoplasia, congenital (MIM# 300200); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.3413 NSDHL Crystle Lee reviewed gene: NSDHL: Rating: GREEN; Mode of pathogenicity: None; Publications: 15689440; Phenotypes: CHILD syndrome (MMIM#308050); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.3413 TFR2 Teresa Zhao reviewed gene: TFR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24847265, 29743178; Phenotypes: Hemochromatosis, type 3 (MIM#604250); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.3413 ORMDL3 Zornitza Stark Marked gene: ORMDL3 as ready
Mendeliome v0.3413 ORMDL3 Zornitza Stark Gene: ormdl3 has been classified as Red List (Low Evidence).
Mendeliome v0.3413 ORMDL3 Zornitza Stark Classified gene: ORMDL3 as Red List (low evidence)
Mendeliome v0.3413 ORMDL3 Zornitza Stark Gene: ormdl3 has been classified as Red List (Low Evidence).
Mendeliome v0.3412 ORMDL3 Zornitza Stark reviewed gene: ORMDL3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Peroxisomal Disorders v0.4 EBP Crystle Lee gene: EBP was added
gene: EBP was added to Peroxisomal Disorders. Sources: Expert Review
Mode of inheritance for gene: EBP 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: EBP were set to 12509714
Phenotypes for gene: EBP were set to Chondrodysplasia punctata, X-linked dominant (MIM#302960)
Review for gene: EBP was set to AMBER
Added comment: Well reported in females with the associated condition.
Sources: Expert Review
Skeletal dysplasia v0.35 EBP Crystle Lee reviewed gene: EBP: Rating: GREEN; Mode of pathogenicity: None; Publications: 12509714; Phenotypes: Chondrodysplasia punctata, X-linked dominant (MIM#302960); Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Peroxisomal Disorders v0.4 FAR1 Crystle Lee gene: FAR1 was added
gene: FAR1 was added to Peroxisomal Disorders. Sources: Expert Review
Mode of inheritance for gene: FAR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAR1 were set to 25439727
Phenotypes for gene: FAR1 were set to Peroxisomal fatty acyl-CoA reductase 1 disorder (MIM#616154)
Review for gene: FAR1 was set to AMBER
Added comment: 3 variants from 2 families reported with the associated phenotype in 2014 with supporting functional studies. Amber pending additional reports.

PMID: 25439727: 3 siblings from 2 families affected by severe ID, early-onset epilepsy, microcephaly, congenital cataracts, growth retardation, and spasticity.
Sources: Expert Review
Peroxisomal Disorders v0.4 ARSE Crystle Lee gene: ARSE was added
gene: ARSE was added to Peroxisomal Disorders. Sources: Expert Review
Mode of inheritance for gene: ARSE was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ARSE were set to 23470839
Phenotypes for gene: ARSE were set to Chondrodysplasia punctata, X-linked recessive (MIM#302950)
Review for gene: ARSE was set to AMBER
Added comment: Well reported in males with Chondrodysplasia punctata due to deficiency of arylsulfatase E activity.
Sources: Expert Review
Peroxisomal Disorders v0.4 AGK Crystle Lee gene: AGK was added
gene: AGK was added to Peroxisomal Disorders. Sources: Expert Review
Mode of inheritance for gene: AGK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AGK were set to 22284826
Phenotypes for gene: AGK were set to Sengers syndrome (MIM#212350)
Review for gene: AGK was set to AMBER
Added comment: >5 families reported with Sengers syndrome, a mitochodrial condition. Unsure if qualifies for inclusion in this panel
Sources: Expert Review
Peroxisomal Disorders v0.4 ACBD5 Crystle Lee reviewed gene: ACBD5: Rating: GREEN; Mode of pathogenicity: None; Publications: 27799409, 23105016; Phenotypes: Retinal dystrophy with leukodystrophy (MIM#618863); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3412 ABCD3 Crystle Lee reviewed gene: ABCD3: Rating: AMBER; Mode of pathogenicity: None; Publications: 25168382; Phenotypes: ?Bile acid synthesis defect, congenital, 5 (MIM#616278); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Peroxisomal Disorders v0.4 ABCD3 Crystle Lee reviewed gene: ABCD3: Rating: RED; Mode of pathogenicity: None; Publications: 25168382; Phenotypes: ?Bile acid synthesis defect, congenital, 5 (MIM#616278); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliopathies v0.193 TBC1D32 Russell Gear reviewed gene: TBC1D32: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 32573025, PMID: 32060556; Phenotypes: Orofacial digital syndrome type IX, syndromic hypopituitarism; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.167 NR0B1 Zornitza Stark Marked gene: NR0B1 as ready
Differences of Sex Development v0.167 NR0B1 Zornitza Stark Gene: nr0b1 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.167 NR0B1 Zornitza Stark Phenotypes for gene: NR0B1 were changed from to 46XY sex reversal 2, dosage-sensitive, MIM# 300018
Differences of Sex Development v0.166 NR0B1 Zornitza Stark Publications for gene: NR0B1 were set to
Differences of Sex Development v0.165 NR0B1 Zornitza Stark Mode of inheritance for gene: NR0B1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Differences of Sex Development v0.164 NR0B1 Zornitza Stark Classified gene: NR0B1 as Amber List (moderate evidence)
Differences of Sex Development v0.164 NR0B1 Zornitza Stark Gene: nr0b1 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.163 NR0B1 Zornitza Stark Tag SV/CNV tag was added to gene: NR0B1.
Differences of Sex Development v0.163 NR0B1 Zornitza Stark reviewed gene: NR0B1: Rating: AMBER; Mode of pathogenicity: None; Publications: 7951319; Phenotypes: 46XY sex reversal 2, dosage-sensitive, MIM# 300018; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Differences of Sex Development v0.161 HOXA13 Zornitza Stark Marked gene: HOXA13 as ready
Differences of Sex Development v0.161 HOXA13 Zornitza Stark Gene: hoxa13 has been classified as Green List (High Evidence).
Differences of Sex Development v0.161 PROKR2 Zornitza Stark Marked gene: PROKR2 as ready
Differences of Sex Development v0.161 PROKR2 Zornitza Stark Gene: prokr2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.161 PROKR2 Zornitza Stark Phenotypes for gene: PROKR2 were changed from to Hypogonadotropic hypogonadism 3 with or without anosmia, MIM# 244200
Differences of Sex Development v0.160 PROKR2 Zornitza Stark Publications for gene: PROKR2 were set to
Differences of Sex Development v0.159 PROKR2 Zornitza Stark Mode of inheritance for gene: PROKR2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3412 NSMF Zornitza Stark Marked gene: NSMF as ready
Mendeliome v0.3412 NSMF Zornitza Stark Gene: nsmf has been classified as Red List (Low Evidence).
Mendeliome v0.3412 NSMF Zornitza Stark Phenotypes for gene: NSMF were changed from to Hypogonadotropic hypogonadism 9 with or without anosmia, MIM# 614838
Mendeliome v0.3411 NSMF Zornitza Stark Publications for gene: NSMF were set to
Mendeliome v0.3410 NSMF Zornitza Stark Mode of inheritance for gene: NSMF was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3409 NSMF Zornitza Stark Classified gene: NSMF as Red List (low evidence)
Mendeliome v0.3409 NSMF Zornitza Stark Gene: nsmf has been classified as Red List (Low Evidence).
Mendeliome v0.3408 NSMF Zornitza Stark reviewed gene: NSMF: Rating: RED; Mode of pathogenicity: None; Publications: 15362570, 17235395, 21700882; Phenotypes: Hypogonadotropic hypogonadism 9 with or without anosmia, MIM# 614838; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Callosome v0.172 NSMF Zornitza Stark Marked gene: NSMF as ready
Callosome v0.172 NSMF Zornitza Stark Gene: nsmf has been classified as Red List (Low Evidence).
Callosome v0.172 NSMF Zornitza Stark Phenotypes for gene: NSMF were changed from to Hypogonadotropic hypogonadism 9 with or without anosmia, MIM# 614838
Callosome v0.171 NSMF Zornitza Stark Mode of inheritance for gene: NSMF was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Callosome v0.170 NSMF Zornitza Stark Classified gene: NSMF as Red List (low evidence)
Callosome v0.170 NSMF Zornitza Stark Gene: nsmf has been classified as Red List (Low Evidence).
Callosome v0.169 NSMF Zornitza Stark reviewed gene: NSMF: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypogonadotropic hypogonadism 9 with or without anosmia, MIM# 614838; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.157 NSMF Zornitza Stark Marked gene: NSMF as ready
Differences of Sex Development v0.157 NSMF Zornitza Stark Gene: nsmf has been classified as Red List (Low Evidence).
Differences of Sex Development v0.157 NSMF Zornitza Stark gene: NSMF was added
gene: NSMF was added to Disorders of Sex Differentiation. Sources: Expert list
Mode of inheritance for gene: NSMF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NSMF were set to 15362570; 17235395; 21700882
Phenotypes for gene: NSMF were set to Hypogonadotropic hypogonadism 9 with or without anosmia, MIM# 614838
Review for gene: NSMF was set to RED
Added comment: Rare variants reported in individuals with IHH; however, variants in other IHH genes also present, and at least one of the variants has a very high population frequency in gnomad (intronic 8-bp deletion ending 14 bp before exon 10 (1159-14_-22del), present in 258 individuals).
Sources: Expert list
Differences of Sex Development v0.156 SPRY4 Zornitza Stark Tag disputed tag was added to gene: SPRY4.
Mendeliome v0.3408 SPRY4 Zornitza Stark Marked gene: SPRY4 as ready
Mendeliome v0.3408 SPRY4 Zornitza Stark Gene: spry4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3408 SPRY4 Zornitza Stark Tag disputed tag was added to gene: SPRY4.
Mendeliome v0.3408 SPRY4 Zornitza Stark Phenotypes for gene: SPRY4 were changed from to Hypogonadotropic hypogonadism 17 with or without anosmia, MIM# 615266
Mendeliome v0.3407 SPRY4 Zornitza Stark Publications for gene: SPRY4 were set to
Mendeliome v0.3406 SPRY4 Zornitza Stark Mode of inheritance for gene: SPRY4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3405 SPRY4 Zornitza Stark Classified gene: SPRY4 as Amber List (moderate evidence)
Mendeliome v0.3405 SPRY4 Zornitza Stark Gene: spry4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3404 SPRY4 Zornitza Stark reviewed gene: SPRY4: Rating: AMBER; Mode of pathogenicity: None; Publications: 23643382; Phenotypes: Hypogonadotropic hypogonadism 17 with or without anosmia, MIM# 615266; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Callosome v0.169 SPRY4 Zornitza Stark Marked gene: SPRY4 as ready
Callosome v0.169 SPRY4 Zornitza Stark Gene: spry4 has been classified as Red List (Low Evidence).
Callosome v0.169 SPRY4 Zornitza Stark Phenotypes for gene: SPRY4 were changed from to Hypogonadotropic hypogonadism 17 with or without anosmia, MIM# 615266
Callosome v0.168 SPRY4 Zornitza Stark Publications for gene: SPRY4 were set to
Callosome v0.167 SPRY4 Zornitza Stark Mode of inheritance for gene: SPRY4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Callosome v0.166 SPRY4 Zornitza Stark Classified gene: SPRY4 as Red List (low evidence)
Callosome v0.166 SPRY4 Zornitza Stark Gene: spry4 has been classified as Red List (Low Evidence).
Callosome v0.165 SPRY4 Zornitza Stark reviewed gene: SPRY4: Rating: RED; Mode of pathogenicity: None; Publications: 23643382; Phenotypes: Hypogonadotropic hypogonadism 17 with or without anosmia, MIM# 615266; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.156 SPRY4 Zornitza Stark Marked gene: SPRY4 as ready
Differences of Sex Development v0.156 SPRY4 Zornitza Stark Gene: spry4 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.156 SPRY4 Zornitza Stark Classified gene: SPRY4 as Amber List (moderate evidence)
Differences of Sex Development v0.156 SPRY4 Zornitza Stark Gene: spry4 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.155 SPRY4 Zornitza Stark gene: SPRY4 was added
gene: SPRY4 was added to Disorders of Sex Differentiation. Sources: Expert list
Mode of inheritance for gene: SPRY4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPRY4 were set to 23643382
Phenotypes for gene: SPRY4 were set to Hypogonadotropic hypogonadism 17 with or without anosmia, MIM# 615266
Review for gene: SPRY4 was set to AMBER
Added comment: 14 unrelated individuals reported originally. Three of these had variants in other IHH genes. The p.Lys177Arg variant is present in 454 individuals in gnomad, p.Ser241Tyr is present in 1279 individuals including 6 homozygotes, p.Val304Ile is present in 457 individuals. These population frequencies cast doubt on the gene-disease relationship.
Sources: Expert list
Mendeliome v0.3404 KISS1 Zornitza Stark Marked gene: KISS1 as ready
Mendeliome v0.3404 KISS1 Zornitza Stark Gene: kiss1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3404 KISS1 Zornitza Stark Phenotypes for gene: KISS1 were changed from to Hypogonadotropic hypogonadism 13 with or without anosmia, MIM# 614842
Mendeliome v0.3403 KISS1 Zornitza Stark Publications for gene: KISS1 were set to
Mendeliome v0.3402 KISS1 Zornitza Stark Mode of inheritance for gene: KISS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3401 KISS1 Zornitza Stark Classified gene: KISS1 as Amber List (moderate evidence)
Mendeliome v0.3401 KISS1 Zornitza Stark Gene: kiss1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3400 KISS1 Zornitza Stark reviewed gene: KISS1: Rating: AMBER; Mode of pathogenicity: None; Publications: 22335740, 25783047, 22766261, 17563351; Phenotypes: Hypogonadotropic hypogonadism 13 with or without anosmia, MIM# 614842; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Callosome v0.165 KISS1 Zornitza Stark Marked gene: KISS1 as ready
Callosome v0.165 KISS1 Zornitza Stark Gene: kiss1 has been classified as Red List (Low Evidence).
Callosome v0.165 KISS1 Zornitza Stark Phenotypes for gene: KISS1 were changed from to Hypogonadotropic hypogonadism 13 with or without anosmia, MIM# 614842
Callosome v0.164 KISS1 Zornitza Stark Publications for gene: KISS1 were set to
Callosome v0.163 KISS1 Zornitza Stark Mode of inheritance for gene: KISS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Callosome v0.162 KISS1 Zornitza Stark Classified gene: KISS1 as Red List (low evidence)
Callosome v0.162 KISS1 Zornitza Stark Gene: kiss1 has been classified as Red List (Low Evidence).
Callosome v0.161 KISS1 Zornitza Stark reviewed gene: KISS1: Rating: RED; Mode of pathogenicity: None; Publications: 22335740, 25783047, 22766261, 17563351; Phenotypes: Hypogonadotropic hypogonadism 13 with or without anosmia, MIM# 614842; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.154 KISS1 Zornitza Stark Marked gene: KISS1 as ready
Differences of Sex Development v0.154 KISS1 Zornitza Stark Gene: kiss1 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.154 KISS1 Zornitza Stark Classified gene: KISS1 as Amber List (moderate evidence)
Differences of Sex Development v0.154 KISS1 Zornitza Stark Gene: kiss1 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.153 KISS1 Zornitza Stark gene: KISS1 was added
gene: KISS1 was added to Disorders of Sex Differentiation. Sources: Expert list
Mode of inheritance for gene: KISS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KISS1 were set to 22335740; 25783047; 22766261; 17563351
Phenotypes for gene: KISS1 were set to Hypogonadotropic hypogonadism 13 with or without anosmia, MIM# 614842
Review for gene: KISS1 was set to AMBER
Added comment: Reported in Turkish families, supportive mouse model, but no variants identified in other cohorts. Role of KISS1 receptor much more established.
Sources: Expert list
Differences of Sex Development v0.152 TACR3 Zornitza Stark Marked gene: TACR3 as ready
Differences of Sex Development v0.152 TACR3 Zornitza Stark Gene: tacr3 has been classified as Green List (High Evidence).
Differences of Sex Development v0.152 TACR3 Zornitza Stark Classified gene: TACR3 as Green List (high evidence)
Differences of Sex Development v0.152 TACR3 Zornitza Stark Gene: tacr3 has been classified as Green List (High Evidence).
Differences of Sex Development v0.151 TACR3 Zornitza Stark gene: TACR3 was added
gene: TACR3 was added to Disorders of Sex Differentiation. Sources: Expert list
Mode of inheritance for gene: TACR3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TACR3 were set to 20332248; 19079066
Phenotypes for gene: TACR3 were set to Hypogonadotropic hypogonadism 11 with or without anosmia, MIM# 614840
Review for gene: TACR3 was set to GREEN
Added comment: Multiple families reported.
Sources: Expert list
Mendeliome v0.3400 INSL3 Zornitza Stark Marked gene: INSL3 as ready
Mendeliome v0.3400 INSL3 Zornitza Stark Gene: insl3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3400 INSL3 Zornitza Stark Phenotypes for gene: INSL3 were changed from to Cryptorchidism, MIM# 219050
Mendeliome v0.3399 INSL3 Zornitza Stark Publications for gene: INSL3 were set to
Mendeliome v0.3398 INSL3 Zornitza Stark Mode of inheritance for gene: INSL3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3397 INSL3 Zornitza Stark Classified gene: INSL3 as Amber List (moderate evidence)
Mendeliome v0.3397 INSL3 Zornitza Stark Gene: insl3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3396 INSL3 Zornitza Stark reviewed gene: INSL3: Rating: AMBER; Mode of pathogenicity: None; Publications: 12601553, 12970298, 11095425; Phenotypes: Cryptorchidism, MIM# 219050; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.150 INSL3 Zornitza Stark Marked gene: INSL3 as ready
Differences of Sex Development v0.150 INSL3 Zornitza Stark Gene: insl3 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.150 INSL3 Zornitza Stark Phenotypes for gene: INSL3 were changed from to Cryptorchidism, MIM# 219050
Differences of Sex Development v0.149 INSL3 Zornitza Stark Publications for gene: INSL3 were set to
Differences of Sex Development v0.148 INSL3 Zornitza Stark Mode of inheritance for gene: INSL3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.147 INSL3 Zornitza Stark Classified gene: INSL3 as Amber List (moderate evidence)
Differences of Sex Development v0.147 INSL3 Zornitza Stark Gene: insl3 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.146 INSL3 Zornitza Stark reviewed gene: INSL3: Rating: AMBER; Mode of pathogenicity: None; Publications: 12601553, 12970298, 11095425; Phenotypes: Cryptorchidism, MIM# 219050; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Callosome v0.161 IL17RD Zornitza Stark Marked gene: IL17RD as ready
Callosome v0.161 IL17RD Zornitza Stark Gene: il17rd has been classified as Red List (Low Evidence).
Callosome v0.161 IL17RD Zornitza Stark Phenotypes for gene: IL17RD were changed from to Hypogonadotropic hypogonadism 18 with or without anosmia, MIM# 615267
Callosome v0.160 IL17RD Zornitza Stark Classified gene: IL17RD as Red List (low evidence)
Callosome v0.160 IL17RD Zornitza Stark Gene: il17rd has been classified as Red List (Low Evidence).
Callosome v0.159 IL17RD Zornitza Stark reviewed gene: IL17RD: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypogonadotropic hypogonadism 18 with or without anosmia, MIM# 615267; Mode of inheritance: None
Mendeliome v0.3396 IL17RD Zornitza Stark Marked gene: IL17RD as ready
Mendeliome v0.3396 IL17RD Zornitza Stark Gene: il17rd has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3396 IL17RD Zornitza Stark Phenotypes for gene: IL17RD were changed from to Hypogonadotropic hypogonadism 18 with or without anosmia, MIM# 615267
Mendeliome v0.3395 IL17RD Zornitza Stark Publications for gene: IL17RD were set to
Mendeliome v0.3394 IL17RD Zornitza Stark Mode of inheritance for gene: IL17RD was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3393 IL17RD Zornitza Stark Classified gene: IL17RD as Amber List (moderate evidence)
Mendeliome v0.3393 IL17RD Zornitza Stark Gene: il17rd has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3392 IL17RD Zornitza Stark reviewed gene: IL17RD: Rating: AMBER; Mode of pathogenicity: None; Publications: 23643382, 32389901; Phenotypes: Hypogonadotropic hypogonadism 18 with or without anosmia, MIM# 615267; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Differences of Sex Development v0.146 IL17RD Zornitza Stark Tag disputed tag was added to gene: IL17RD.
Differences of Sex Development v0.146 IL17RD Zornitza Stark Marked gene: IL17RD as ready
Differences of Sex Development v0.146 IL17RD Zornitza Stark Gene: il17rd has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.146 IL17RD Zornitza Stark Phenotypes for gene: IL17RD were changed from to Hypogonadotropic hypogonadism 18 with or without anosmia, MIM# 615267
Differences of Sex Development v0.145 IL17RD Zornitza Stark Publications for gene: IL17RD were set to
Differences of Sex Development v0.144 IL17RD Zornitza Stark Mode of inheritance for gene: IL17RD was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Differences of Sex Development v0.143 IL17RD Zornitza Stark Classified gene: IL17RD as Amber List (moderate evidence)
Differences of Sex Development v0.143 IL17RD Zornitza Stark Gene: il17rd has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.142 IL17RD Zornitza Stark edited their review of gene: IL17RD: Changed rating: AMBER
Differences of Sex Development v0.142 IL17RD Zornitza Stark reviewed gene: IL17RD: Rating: GREEN; Mode of pathogenicity: None; Publications: 23643382, 32389901; Phenotypes: Hypogonadotropic hypogonadism 18 with or without anosmia, MIM# 615267; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Differences of Sex Development v0.142 HSD17B4 Zornitza Stark Marked gene: HSD17B4 as ready
Differences of Sex Development v0.142 HSD17B4 Zornitza Stark Gene: hsd17b4 has been classified as Green List (High Evidence).
Differences of Sex Development v0.142 HSD17B4 Zornitza Stark Phenotypes for gene: HSD17B4 were changed from to Perrault syndrome 1, MIM# 233400
Differences of Sex Development v0.141 HSD17B4 Zornitza Stark Publications for gene: HSD17B4 were set to
Differences of Sex Development v0.140 HSD17B4 Zornitza Stark Mode of inheritance for gene: HSD17B4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.139 HSD17B4 Zornitza Stark reviewed gene: HSD17B4: Rating: GREEN; Mode of pathogenicity: None; Publications: 24553428, 23181892; Phenotypes: Perrault syndrome 1, MIM# 233400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Callosome v0.159 HS6ST1 Zornitza Stark Marked gene: HS6ST1 as ready
Callosome v0.159 HS6ST1 Zornitza Stark Gene: hs6st1 has been classified as Red List (Low Evidence).
Callosome v0.159 HS6ST1 Zornitza Stark Phenotypes for gene: HS6ST1 were changed from to {Hypogonadotropic hypogonadism 15 with or without anosmia} 614880
Callosome v0.158 HS6ST1 Zornitza Stark Publications for gene: HS6ST1 were set to
Callosome v0.157 HS6ST1 Zornitza Stark Mode of inheritance for gene: HS6ST1 was changed from Unknown to Other
Callosome v0.156 HS6ST1 Zornitza Stark Classified gene: HS6ST1 as Red List (low evidence)
Callosome v0.156 HS6ST1 Zornitza Stark Gene: hs6st1 has been classified as Red List (Low Evidence).
Callosome v0.155 HS6ST1 Zornitza Stark reviewed gene: HS6ST1: Rating: RED; Mode of pathogenicity: None; Publications: 21700882; Phenotypes: {Hypogonadotropic hypogonadism 15 with or without anosmia} 614880; Mode of inheritance: Other
Mendeliome v0.3392 HS6ST1 Zornitza Stark Mode of inheritance for gene: HS6ST1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to Other
Mendeliome v0.3391 HS6ST1 Zornitza Stark edited their review of gene: HS6ST1: Changed mode of inheritance: Other
Mendeliome v0.3391 HS6ST1 Zornitza Stark Marked gene: HS6ST1 as ready
Mendeliome v0.3391 HS6ST1 Zornitza Stark Gene: hs6st1 has been classified as Red List (Low Evidence).
Mendeliome v0.3391 HS6ST1 Zornitza Stark Phenotypes for gene: HS6ST1 were changed from to {Hypogonadotropic hypogonadism 15 with or without anosmia} 614880
Mendeliome v0.3390 HS6ST1 Zornitza Stark Publications for gene: HS6ST1 were set to
Mendeliome v0.3389 HS6ST1 Zornitza Stark Mode of inheritance for gene: HS6ST1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3388 HS6ST1 Zornitza Stark Classified gene: HS6ST1 as Red List (low evidence)
Mendeliome v0.3388 HS6ST1 Zornitza Stark Gene: hs6st1 has been classified as Red List (Low Evidence).
Mendeliome v0.3387 HS6ST1 Zornitza Stark reviewed gene: HS6ST1: Rating: RED; Mode of pathogenicity: None; Publications: 21700882; Phenotypes: {Hypogonadotropic hypogonadism 15 with or without anosmia} 614880; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.139 HS6ST1 Zornitza Stark Marked gene: HS6ST1 as ready
Differences of Sex Development v0.139 HS6ST1 Zornitza Stark Gene: hs6st1 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.139 HS6ST1 Zornitza Stark Phenotypes for gene: HS6ST1 were changed from to {Hypogonadotropic hypogonadism 15 with or without anosmia} 614880
Differences of Sex Development v0.138 HS6ST1 Zornitza Stark Publications for gene: HS6ST1 were set to
Differences of Sex Development v0.137 HS6ST1 Zornitza Stark Mode of inheritance for gene: HS6ST1 was changed from Unknown to Other
Differences of Sex Development v0.136 HS6ST1 Zornitza Stark Classified gene: HS6ST1 as Red List (low evidence)
Differences of Sex Development v0.136 HS6ST1 Zornitza Stark Gene: hs6st1 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.135 HS6ST1 Zornitza Stark reviewed gene: HS6ST1: Rating: RED; Mode of pathogenicity: None; Publications: 21700882; Phenotypes: {Hypogonadotropic hypogonadism 15 with or without anosmia} 614880; Mode of inheritance: Other
Differences of Sex Development v0.135 HOXA13 Zornitza Stark Phenotypes for gene: HOXA13 were changed from to Hand-foot-uterus syndrome, MIM# 140000
Differences of Sex Development v0.134 HOXA13 Zornitza Stark Publications for gene: HOXA13 were set to
Differences of Sex Development v0.133 HOXA13 Zornitza Stark Mode of inheritance for gene: HOXA13 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.132 HOXA13 Zornitza Stark reviewed gene: HOXA13: Rating: GREEN; Mode of pathogenicity: None; Publications: 10839976, 9020844; Phenotypes: Hand-foot-uterus syndrome, MIM# 140000; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.132 HESX1 Zornitza Stark Marked gene: HESX1 as ready
Differences of Sex Development v0.132 HESX1 Zornitza Stark Gene: hesx1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.132 HESX1 Zornitza Stark Phenotypes for gene: HESX1 were changed from to Pituitary hormone deficiency, combined, 5, MIM# 182230
Differences of Sex Development v0.131 HESX1 Zornitza Stark Mode of inheritance for gene: HESX1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Differences of Sex Development v0.130 HESX1 Zornitza Stark reviewed gene: HESX1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pituitary hormone deficiency, combined, 5, MIM# 182230; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Callosome v0.155 GNRH1 Zornitza Stark Marked gene: GNRH1 as ready
Callosome v0.155 GNRH1 Zornitza Stark Gene: gnrh1 has been classified as Red List (Low Evidence).
Callosome v0.155 GNRH1 Zornitza Stark Phenotypes for gene: GNRH1 were changed from to Hypogonadotropic hypogonadism 12 with or without anosmia, MIM# 614841
Callosome v0.154 GNRH1 Zornitza Stark Mode of inheritance for gene: GNRH1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Callosome v0.153 GNRH1 Zornitza Stark Classified gene: GNRH1 as Red List (low evidence)
Callosome v0.153 GNRH1 Zornitza Stark Gene: gnrh1 has been classified as Red List (Low Evidence).
Callosome v0.152 GNRH1 Zornitza Stark reviewed gene: GNRH1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypogonadotropic hypogonadism 12 with or without anosmia, MIM# 614841; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3387 GNRH1 Zornitza Stark Marked gene: GNRH1 as ready
Mendeliome v0.3387 GNRH1 Zornitza Stark Gene: gnrh1 has been classified as Green List (High Evidence).
Mendeliome v0.3387 GNRH1 Zornitza Stark Phenotypes for gene: GNRH1 were changed from to Hypogonadotropic hypogonadism 12 with or without anosmia, MIM# 614841
Mendeliome v0.3386 GNRH1 Zornitza Stark Publications for gene: GNRH1 were set to
Mendeliome v0.3385 GNRH1 Zornitza Stark Mode of inheritance for gene: GNRH1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3384 GNRH1 Zornitza Stark reviewed gene: GNRH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19535795, 19567835, 32134721, 31200363, 26595427; Phenotypes: Hypogonadotropic hypogonadism 12 with or without anosmia, MIM# 614841; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.130 GNRH1 Zornitza Stark Marked gene: GNRH1 as ready
Differences of Sex Development v0.130 GNRH1 Zornitza Stark Gene: gnrh1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.130 GNRH1 Zornitza Stark Phenotypes for gene: GNRH1 were changed from to Hypogonadotropic hypogonadism 12 with or without anosmia, MIM# 614841
Differences of Sex Development v0.129 GNRH1 Zornitza Stark Publications for gene: GNRH1 were set to
Differences of Sex Development v0.128 GNRH1 Zornitza Stark Mode of inheritance for gene: GNRH1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.127 GNRH1 Zornitza Stark reviewed gene: GNRH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19535795, 19567835, 32134721, 31200363, 26595427; Phenotypes: Hypogonadotropic hypogonadism 12 with or without anosmia, MIM# 614841; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2776 ZNF462 Zornitza Stark Phenotypes for gene: ZNF462 were changed from Weiss-Kruszka syndrome; OMIM# 618619 to Weiss-Kruszka syndrome, OMIM# 618619
Intellectual disability syndromic and non-syndromic v0.2775 ZNF462 Zornitza Stark Publications for gene: ZNF462 were set to PubMed: 31361404; 28513610
Mendeliome v0.3384 KIF3B Zornitza Stark Phenotypes for gene: KIF3B were changed from hepatic fibrosis; retinitis pigmentosa; postaxial polydactyly to hepatic fibrosis; retinitis pigmentosa; postaxial polydactyly; Retinitis pigmentosa 89, MIM#618955
Mendeliome v0.3383 KIF3B Zornitza Stark edited their review of gene: KIF3B: Changed phenotypes: hepatic fibrosis, retinitis pigmentosa, postaxial polydactyly, Retinitis pigmentosa 89, MIM#618955
Ciliopathies v0.193 KIF3B Zornitza Stark Phenotypes for gene: KIF3B were changed from hepatic fibrosis; retinitis pigmentosa; postaxial polydactyly to hepatic fibrosis; retinitis pigmentosa; postaxial polydactyly; Retinitis pigmentosa 89, MIM#618955
Ciliopathies v0.192 KIF3B Zornitza Stark edited their review of gene: KIF3B: Changed phenotypes: hepatic fibrosis, retinitis pigmentosa, postaxial polydactyly, Retinitis pigmentosa 89, MIM#618955
Genetic Epilepsy v0.756 CUX2 Zornitza Stark Marked gene: CUX2 as ready
Genetic Epilepsy v0.756 CUX2 Zornitza Stark Gene: cux2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.756 CUX2 Zornitza Stark Phenotypes for gene: CUX2 were changed from to Epileptic encephalopathy, early infantile, 67, MIM#618141
Genetic Epilepsy v0.755 CUX2 Zornitza Stark Publications for gene: CUX2 were set to
Genetic Epilepsy v0.754 CUX2 Zornitza Stark Mode of inheritance for gene: CUX2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.753 CUX2 Zornitza Stark reviewed gene: CUX2: Rating: GREEN; Mode of pathogenicity: None; Publications: 2963073, 29795476; Phenotypes: Epileptic encephalopathy, early infantile, 67, MIM#618141; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3383 CUX2 Zornitza Stark Marked gene: CUX2 as ready
Mendeliome v0.3383 CUX2 Zornitza Stark Added comment: Comment when marking as ready: At least 10 individuals reported with same recurrent de novo missense variant.
Mendeliome v0.3383 CUX2 Zornitza Stark Gene: cux2 has been classified as Green List (High Evidence).
Mendeliome v0.3383 CUX2 Zornitza Stark Phenotypes for gene: CUX2 were changed from to Epileptic encephalopathy, early infantile, 67, MIM#618141
Mendeliome v0.3382 CUX2 Zornitza Stark Publications for gene: CUX2 were set to
Mendeliome v0.3381 CUX2 Zornitza Stark Mode of inheritance for gene: CUX2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Disorders of Glycosylation v0.96 DPM1 Zornitza Stark Marked gene: DPM1 as ready
Congenital Disorders of Glycosylation v0.96 DPM1 Zornitza Stark Gene: dpm1 has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v0.96 DPM1 Zornitza Stark Phenotypes for gene: DPM1 were changed from to Congenital disorder of glycosylation, type Ie, MIM# 608799
Congenital Disorders of Glycosylation v0.95 DPM1 Zornitza Stark Publications for gene: DPM1 were set to
Congenital Disorders of Glycosylation v0.94 DPM1 Zornitza Stark Mode of inheritance for gene: DPM1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.93 DPM1 Zornitza Stark reviewed gene: DPM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23856421, 16641202, 10642602, 10642597; Phenotypes: Congenital disorder of glycosylation, type Ie, 608799; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3380 DPM1 Zornitza Stark Marked gene: DPM1 as ready
Mendeliome v0.3380 DPM1 Zornitza Stark Gene: dpm1 has been classified as Green List (High Evidence).
Mendeliome v0.3380 DPM1 Zornitza Stark Phenotypes for gene: DPM1 were changed from to Congenital disorder of glycosylation, type Ie, 608799
Mendeliome v0.3379 DPM1 Zornitza Stark Publications for gene: DPM1 were set to
Mendeliome v0.3378 DPM1 Zornitza Stark Mode of inheritance for gene: DPM1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3377 CUX2 Elena Savva reviewed gene: CUX2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 2963073, 29795476; Phenotypes: Epileptic encephalopathy, early infantile, 67, 618141; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Periventricular Grey Matter Heterotopia v0.10 Bryony Thompson Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Mendeliome v0.3377 DPM1 Elena Savva reviewed gene: DPM1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 23856421; Phenotypes: Congenital disorder of glycosylation, type Ie, 608799; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3377 GIPC1 Zornitza Stark Marked gene: GIPC1 as ready
Mendeliome v0.3377 GIPC1 Zornitza Stark Gene: gipc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3377 GIPC1 Zornitza Stark Classified gene: GIPC1 as Amber List (moderate evidence)
Mendeliome v0.3377 GIPC1 Zornitza Stark Gene: gipc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3376 GIPC1 Zornitza Stark gene: GIPC1 was added
gene: GIPC1 was added to Mendeliome. Sources: Literature
5'UTR, STR tags were added to gene: GIPC1.
Mode of inheritance for gene: GIPC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GIPC1 were set to 32413282
Phenotypes for gene: GIPC1 were set to Oculopharyngodistal myopathy-2 (OPDM2), MIM#618940
Review for gene: GIPC1 was set to AMBER
Added comment: 19 families reported with heterozygous trinucleotide repeat expansion in the 5-prime untranslated region and onset of distal muscle weakness, mainly of the lower limbs, and/or ophthalmoplegia in the second or third decades of life. Note this is unlikely to be tractable currently by most NGS assays.
Sources: Literature
Mendeliome v0.3375 SMC3 Zornitza Stark Marked gene: SMC3 as ready
Mendeliome v0.3375 SMC3 Zornitza Stark Gene: smc3 has been classified as Green List (High Evidence).
Mendeliome v0.3375 SMC3 Zornitza Stark Phenotypes for gene: SMC3 were changed from to Cornelia de Lange syndrome 3, MIM#610759
Mendeliome v0.3374 SMC3 Zornitza Stark Publications for gene: SMC3 were set to
Mendeliome v0.3373 SMC3 Zornitza Stark Mode of inheritance for gene: SMC3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2774 DEAF1 Zornitza Stark Marked gene: DEAF1 as ready
Intellectual disability syndromic and non-syndromic v0.2774 DEAF1 Zornitza Stark Gene: deaf1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2774 DEAF1 Zornitza Stark Phenotypes for gene: DEAF1 were changed from to Neurodevelopmental disorder with hypotonia, impaired expressive language, and with or without seizures 617171; Vulto-van Silfout-de Vries syndrome 615828
Intellectual disability syndromic and non-syndromic v0.2773 DEAF1 Zornitza Stark Publications for gene: DEAF1 were set to
Intellectual disability syndromic and non-syndromic v0.2772 DEAF1 Zornitza Stark Mode of inheritance for gene: DEAF1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2771 DEAF1 Zornitza Stark reviewed gene: DEAF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30923367, 24726472, 26048982, 28940898, 26834045; Phenotypes: Neurodevelopmental disorder with hypotonia, impaired expressive language, and with or without seizures 617171, Vulto-van Silfout-de Vries syndrome 615828; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3372 DEAF1 Zornitza Stark Marked gene: DEAF1 as ready
Mendeliome v0.3372 DEAF1 Zornitza Stark Gene: deaf1 has been classified as Green List (High Evidence).
Mendeliome v0.3372 DEAF1 Zornitza Stark Phenotypes for gene: DEAF1 were changed from to Neurodevelopmental disorder with hypotonia, impaired expressive language, and with or without seizures 617171; Vulto-van Silfout-de Vries syndrome 615828
Mendeliome v0.3371 DEAF1 Zornitza Stark Publications for gene: DEAF1 were set to
Mendeliome v0.3370 DEAF1 Zornitza Stark Mode of pathogenicity for gene: DEAF1 was changed from to Other
Mendeliome v0.3369 DEAF1 Zornitza Stark Mode of inheritance for gene: DEAF1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Multiple pterygium syndrome_Fetal akinesia sequence v0.3 RIPK4 Zornitza Stark Marked gene: RIPK4 as ready
Multiple pterygium syndrome_Fetal akinesia sequence v0.3 RIPK4 Zornitza Stark Gene: ripk4 has been classified as Green List (High Evidence).
Multiple pterygium syndrome_Fetal akinesia sequence v0.3 RIPK4 Zornitza Stark Classified gene: RIPK4 as Green List (high evidence)
Multiple pterygium syndrome_Fetal akinesia sequence v0.3 RIPK4 Zornitza Stark Gene: ripk4 has been classified as Green List (High Evidence).
Multiple pterygium syndrome_Fetal akinesia sequence v0.2 RIPK4 Zornitza Stark gene: RIPK4 was added
gene: RIPK4 was added to Multiple pterygium syndrome. Sources: Expert Review
Mode of inheritance for gene: RIPK4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RIPK4 were set to 28940926; 22197489; 22197488
Phenotypes for gene: RIPK4 were set to Popliteal pterygium syndrome, Bartsocas-Papas type, MIM# 263650
Review for gene: RIPK4 was set to GREEN
Added comment: At least three unrelated families reported.
Sources: Expert Review
Arthrogryposis v0.189 RIPK4 Zornitza Stark Marked gene: RIPK4 as ready
Arthrogryposis v0.189 RIPK4 Zornitza Stark Gene: ripk4 has been classified as Green List (High Evidence).
Arthrogryposis v0.189 RIPK4 Zornitza Stark Phenotypes for gene: RIPK4 were changed from to Popliteal pterygium syndrome, Bartsocas-Papas type, MIM# 263650
Arthrogryposis v0.188 RIPK4 Zornitza Stark Publications for gene: RIPK4 were set to
Arthrogryposis v0.187 RIPK4 Zornitza Stark Mode of inheritance for gene: RIPK4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.186 RIPK4 Zornitza Stark reviewed gene: RIPK4: Rating: GREEN; Mode of pathogenicity: None; Publications: 28940926, 22197489, 22197488; Phenotypes: Popliteal pterygium syndrome, Bartsocas-Papas type, MIM# 263650; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3368 SMC3 Elena Savva reviewed gene: SMC3: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 18996922, 25655089, 31334757; Phenotypes: ornelia de Lange syndrome 3, 610759; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.3368 DEAF1 Elena Savva reviewed gene: DEAF1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID 30923367, PMID 24726472; Phenotypes: Neurodevelopmental disorder with hypotonia, impaired expressive language, and with or without seizures 617171, Vulto-van Silfout-de Vries syndrome 615828; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.753 GRM7 Zornitza Stark Phenotypes for gene: GRM7 were changed from Epilepsy, microcephaly, developmental delay to Epilepsy, microcephaly, developmental delay; neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities (NEDSHBA), MIM#618922
Microcephaly v0.140 GRM7 Zornitza Stark Phenotypes for gene: GRM7 were changed from Epilepsy, microcephaly, developmental delay to Epilepsy, microcephaly, developmental delay; neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities (NEDSHBA), MIM#618922
Microcephaly v0.139 GRM7 Zornitza Stark edited their review of gene: GRM7: Changed phenotypes: Epilepsy, microcephaly, developmental delay, neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities (NEDSHBA), MIM#618922
Mendeliome v0.3368 GRM7 Zornitza Stark Phenotypes for gene: GRM7 were changed from Epilepsy, microcephaly, developmental delay to Epilepsy, microcephaly, developmental delay; neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities (NEDSHBA), MIM#618922
Mendeliome v0.3367 GRM7 Zornitza Stark edited their review of gene: GRM7: Changed phenotypes: Epilepsy, microcephaly, developmental delay, neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities (NEDSHBA), MIM#618922
Intellectual disability syndromic and non-syndromic v0.2771 GRM7 Zornitza Stark Phenotypes for gene: GRM7 were changed from Epilepsy, microcephaly, developmental delay to Epilepsy, microcephaly, developmental delay; neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities (NEDSHBA), MIM#618922
Intellectual disability syndromic and non-syndromic v0.2770 GRM7 Zornitza Stark edited their review of gene: GRM7: Changed phenotypes: Epilepsy, microcephaly, developmental delay, neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities (NEDSHBA), MIM#618922
Mendeliome v0.3367 CLCC1 Zornitza Stark Phenotypes for gene: CLCC1 were changed from Retinitis pigmentosa 32 to Retinitis pigmentosa 32, MIM# 609913
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.56 CLCC1 Zornitza Stark Phenotypes for gene: CLCC1 were changed from Retinitis pigmentosa 32 to Retinitis pigmentosa 32, MIM# 609913
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.55 CLCC1 Zornitza Stark reviewed gene: CLCC1: Rating: AMBER; Mode of pathogenicity: None; Publications: 30157172; Phenotypes: Retinitis pigmentosa 32, MIM# 609913; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3366 ABCC9 Zornitza Stark Marked gene: ABCC9 as ready
Mendeliome v0.3366 ABCC9 Zornitza Stark Gene: abcc9 has been classified as Green List (High Evidence).
Mendeliome v0.3366 ABCC9 Zornitza Stark Phenotypes for gene: ABCC9 were changed from to Hypertrichotic osteochondrodysplasia, MIM# 239850; Cantu syndrome; mild ID, similar facies, myopathy, cerebral white matter hyperintensities; cardiac systolic dysfunction
Mendeliome v0.3365 ABCC9 Zornitza Stark Publications for gene: ABCC9 were set to
Mendeliome v0.3364 ABCC9 Zornitza Stark Mode of inheritance for gene: ABCC9 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3363 ABCC9 Zornitza Stark reviewed gene: ABCC9: Rating: GREEN; Mode of pathogenicity: Other; Publications: 31575858, 22610116, 22608503; Phenotypes: Hypertrichotic osteochondrodysplasia, MIM# 239850, Cantu syndrome, mild ID, similar facies, myopathy, cerebral white matter hyperintensities, cardiac systolic dysfunction; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Disorders of Glycosylation v0.93 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Rare Disease
Differences of Sex Development v0.127 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Rare Disease
Mendeliome v0.3363 TSPYL1 Zornitza Stark Marked gene: TSPYL1 as ready
Mendeliome v0.3363 TSPYL1 Zornitza Stark Gene: tspyl1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3363 TSPYL1 Zornitza Stark Phenotypes for gene: TSPYL1 were changed from to Sudden infant death with dysgenesis of the testes syndrome (MIM#608800)
Mendeliome v0.3362 TSPYL1 Zornitza Stark Publications for gene: TSPYL1 were set to
Mendeliome v0.3361 TSPYL1 Zornitza Stark Mode of inheritance for gene: TSPYL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3360 TSPYL1 Zornitza Stark Classified gene: TSPYL1 as Amber List (moderate evidence)
Mendeliome v0.3360 TSPYL1 Zornitza Stark Gene: tspyl1 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.126 TSPYL1 Zornitza Stark Tag disputed tag was added to gene: TSPYL1.
Mendeliome v0.3359 TSPYL1 Zornitza Stark reviewed gene: TSPYL1: Rating: AMBER; Mode of pathogenicity: None; Publications: 15273283, 19463995, 22137496, 25449952, 16418600; Phenotypes: Sudden infant death with dysgenesis of the testes syndrome (MIM#608800); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.126 TSPYL1 Zornitza Stark Classified gene: TSPYL1 as Amber List (moderate evidence)
Differences of Sex Development v0.126 TSPYL1 Zornitza Stark Gene: tspyl1 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.125 TSPYL1 Zornitza Stark Marked gene: TSPYL1 as ready
Differences of Sex Development v0.125 TSPYL1 Zornitza Stark Gene: tspyl1 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.125 TSPYL1 Zornitza Stark Phenotypes for gene: TSPYL1 were changed from to Sudden infant death with dysgenesis of the testes syndrome (MIM#608800)
Differences of Sex Development v0.124 TSPYL1 Zornitza Stark Publications for gene: TSPYL1 were set to
Differences of Sex Development v0.123 TSPYL1 Zornitza Stark Mode of inheritance for gene: TSPYL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.122 TSPYL1 Zornitza Stark Classified gene: TSPYL1 as Red List (low evidence)
Differences of Sex Development v0.122 TSPYL1 Zornitza Stark Gene: tspyl1 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.121 WDR11 Zornitza Stark Marked gene: WDR11 as ready
Differences of Sex Development v0.121 WDR11 Zornitza Stark Gene: wdr11 has been classified as Green List (High Evidence).
Differences of Sex Development v0.121 WDR11 Zornitza Stark Phenotypes for gene: WDR11 were changed from to Hypogonadotropic hypogonadism 14 with or without anosmia, MIM#614858
Differences of Sex Development v0.120 WDR11 Zornitza Stark Publications for gene: WDR11 were set to
Differences of Sex Development v0.119 WDR11 Zornitza Stark Mode of inheritance for gene: WDR11 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.118 KISS1R Zornitza Stark Marked gene: KISS1R as ready
Differences of Sex Development v0.118 KISS1R Zornitza Stark Gene: kiss1r has been classified as Green List (High Evidence).
Differences of Sex Development v0.118 KISS1R Zornitza Stark Phenotypes for gene: KISS1R were changed from to Hypogonadotropic hypogonadism 8 with or without anosmia (MIM#614837)
Differences of Sex Development v0.117 KISS1R Zornitza Stark Publications for gene: KISS1R were set to
Differences of Sex Development v0.116 KISS1R Zornitza Stark Mode of inheritance for gene: KISS1R was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.92 PIGM Zornitza Stark Phenotypes for gene: PIGM were changed from portal vein thrombosis; persistent absence seizures; macrocephaly; infantile-onset cerebrovascular thrombotic events; portal vein thrombosis; persistent absence seizures; macrocephaly; infantile-onset cerebrovascular thrombotic events to portal vein thrombosis; persistent absence seizures; macrocephaly; infantile-onset cerebrovascular thrombotic events; portal vein thrombosis; persistent absence seizures; macrocephaly; infantile-onset cerebrovascular thrombotic events
Congenital Disorders of Glycosylation v0.92 PIGM Zornitza Stark Phenotypes for gene: PIGM were changed from portal vein thrombosis; persistent absence seizures; macrocephaly; infantile-onset cerebrovascular thrombotic events to portal vein thrombosis; persistent absence seizures; macrocephaly; infantile-onset cerebrovascular thrombotic events; portal vein thrombosis; persistent absence seizures; macrocephaly; infantile-onset cerebrovascular thrombotic events
Mendeliome v0.3359 PIGM Zornitza Stark Marked gene: PIGM as ready
Mendeliome v0.3359 PIGM Zornitza Stark Gene: pigm has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3359 PIGM Zornitza Stark Phenotypes for gene: PIGM were changed from to Glycosylphosphatidylinositol deficiency, MIM# 610293; portal vein thrombosis; persistent absence seizures; macrocephaly; infantile-onset cerebrovascular thrombotic events
Mendeliome v0.3358 PIGM Zornitza Stark Publications for gene: PIGM were set to
Mendeliome v0.3357 PIGM Zornitza Stark Mode of inheritance for gene: PIGM was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3356 PIGM Zornitza Stark Classified gene: PIGM as Amber List (moderate evidence)
Mendeliome v0.3356 PIGM Zornitza Stark Gene: pigm has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3355 PIGM Zornitza Stark Tag founder tag was added to gene: PIGM.
Differences of Sex Development v0.115 LEP Zornitza Stark Marked gene: LEP as ready
Differences of Sex Development v0.115 LEP Zornitza Stark Gene: lep has been classified as Green List (High Evidence).
Mendeliome v0.3355 LEP Zornitza Stark Marked gene: LEP as ready
Mendeliome v0.3355 LEP Zornitza Stark Gene: lep has been classified as Green List (High Evidence).
Mendeliome v0.3355 LEP Zornitza Stark Phenotypes for gene: LEP were changed from to Obesity, morbid, due to leptin deficiency (MIM#614962)
Mendeliome v0.3354 LEP Zornitza Stark Publications for gene: LEP were set to
Mendeliome v0.3353 LEP Zornitza Stark Mode of inheritance for gene: LEP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.115 LEP Zornitza Stark Phenotypes for gene: LEP were changed from Obesity, morbid, due to leptin deficiency (MIM#614962) to Obesity, morbid, due to leptin deficiency (MIM#614962)
Congenital Disorders of Glycosylation v0.91 ST3GAL3 Zornitza Stark Marked gene: ST3GAL3 as ready
Congenital Disorders of Glycosylation v0.91 ST3GAL3 Zornitza Stark Gene: st3gal3 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.115 LEP Zornitza Stark Phenotypes for gene: LEP were changed from to Obesity, morbid, due to leptin deficiency (MIM#614962)
Differences of Sex Development v0.114 LEP Zornitza Stark Publications for gene: LEP were set to
Differences of Sex Development v0.113 LEP Zornitza Stark Mode of inheritance for gene: LEP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.91 NUS1 Zornitza Stark Marked gene: NUS1 as ready
Congenital Disorders of Glycosylation v0.91 NUS1 Zornitza Stark Gene: nus1 has been classified as Amber List (Moderate Evidence).
Congenital Disorders of Glycosylation v0.91 ST3GAL3 Zornitza Stark Phenotypes for gene: ST3GAL3 were changed from to Mental retardation, autosomal recessive 12 MIM# 611090
Congenital Disorders of Glycosylation v0.91 NUS1 Zornitza Stark Publications for gene: NUS1 were set to
Mendeliome v0.3352 LEPR Zornitza Stark Marked gene: LEPR as ready
Mendeliome v0.3352 LEPR Zornitza Stark Gene: lepr has been classified as Green List (High Evidence).
Mendeliome v0.3352 LEPR Zornitza Stark Phenotypes for gene: LEPR were changed from to Obesity, morbid, due to leptin receptor deficiency (MIM#614963)
Mendeliome v0.3351 LEPR Zornitza Stark Publications for gene: LEPR were set to
Mendeliome v0.3350 LEPR Zornitza Stark Mode of inheritance for gene: LEPR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.112 LEPR Zornitza Stark Marked gene: LEPR as ready
Differences of Sex Development v0.112 LEPR Zornitza Stark Gene: lepr has been classified as Green List (High Evidence).
Differences of Sex Development v0.112 LEPR Zornitza Stark Phenotypes for gene: LEPR were changed from to Obesity, morbid, due to leptin receptor deficiency (MIM#614963)
Differences of Sex Development v0.111 LEPR Zornitza Stark Publications for gene: LEPR were set to
Differences of Sex Development v0.110 LEPR Zornitza Stark Mode of inheritance for gene: LEPR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.109 FGF17 Zornitza Stark Marked gene: FGF17 as ready
Differences of Sex Development v0.109 FGF17 Zornitza Stark Added comment: Comment when marking as ready: Borderline Green/Amber: contribution may not be monogenic.
Differences of Sex Development v0.109 FGF17 Zornitza Stark Gene: fgf17 has been classified as Green List (High Evidence).
Differences of Sex Development v0.109 FGF17 Zornitza Stark Publications for gene: FGF17 were set to
Differences of Sex Development v0.108 FGF17 Zornitza Stark Mode of inheritance for gene: FGF17 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.107 FGF17 Zornitza Stark reviewed gene: FGF17: Rating: GREEN; Mode of pathogenicity: None; Publications: 23643382, 31748124; Phenotypes: Hypogonadotropic hypogonadism 20 with or without anosmia, MIM# 615270; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.107 LHB Zornitza Stark Marked gene: LHB as ready
Differences of Sex Development v0.107 LHB Zornitza Stark Gene: lhb has been classified as Green List (High Evidence).
Differences of Sex Development v0.107 LHB Zornitza Stark Phenotypes for gene: LHB were changed from to Hypogonadotropic hypogonadism 23 with or without anosmia (MIM#228300)
Differences of Sex Development v0.106 LHB Zornitza Stark Publications for gene: LHB were set to
Differences of Sex Development v0.105 LHB Zornitza Stark Mode of inheritance for gene: LHB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.104 FEZF1 Zornitza Stark Marked gene: FEZF1 as ready
Differences of Sex Development v0.104 FEZF1 Zornitza Stark Gene: fezf1 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.104 FEZF1 Zornitza Stark Phenotypes for gene: FEZF1 were changed from to Hypogonadotropic hypogonadism 22, with or without anosmia 616030
Differences of Sex Development v0.103 FEZF1 Zornitza Stark Publications for gene: FEZF1 were set to
Differences of Sex Development v0.102 FEZF1 Zornitza Stark Mode of inheritance for gene: FEZF1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.101 FEZF1 Zornitza Stark Classified gene: FEZF1 as Amber List (moderate evidence)
Differences of Sex Development v0.101 FEZF1 Zornitza Stark Gene: fezf1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3349 FEZF1 Zornitza Stark Marked gene: FEZF1 as ready
Mendeliome v0.3349 FEZF1 Zornitza Stark Gene: fezf1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3349 FEZF1 Zornitza Stark Phenotypes for gene: FEZF1 were changed from to Hypogonadotropic hypogonadism 22, with or without anosmia, MIM# 616030
Mendeliome v0.3348 FEZF1 Zornitza Stark Publications for gene: FEZF1 were set to
Mendeliome v0.3347 FEZF1 Zornitza Stark Mode of inheritance for gene: FEZF1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3346 FEZF1 Zornitza Stark Classified gene: FEZF1 as Amber List (moderate evidence)
Mendeliome v0.3346 FEZF1 Zornitza Stark Gene: fezf1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3345 ESR2 Zornitza Stark Marked gene: ESR2 as ready
Mendeliome v0.3345 ESR2 Zornitza Stark Gene: esr2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3345 ESR2 Zornitza Stark Phenotypes for gene: ESR2 were changed from to 46,XY disorder of sex development; Ovarian dysgenesis 8, MIM# 618187
Mendeliome v0.3344 ESR2 Zornitza Stark Publications for gene: ESR2 were set to
Mendeliome v0.3343 ESR2 Zornitza Stark Mode of inheritance for gene: ESR2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3342 ESR2 Zornitza Stark reviewed gene: ESR2: Rating: AMBER; Mode of pathogenicity: None; Publications: 29261182, 9861029, 30113650; Phenotypes: 46,XY disorder of sex development, Ovarian dysgenesis 8, MIM# 618187; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.90 NUS1 Zornitza Stark Phenotypes for gene: NUS1 were changed from to Congenital disorder of glycosylation, type 1aa, MIM#610463
Differences of Sex Development v0.100 ESR2 Zornitza Stark Marked gene: ESR2 as ready
Differences of Sex Development v0.100 ESR2 Zornitza Stark Gene: esr2 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.100 ESR2 Zornitza Stark Phenotypes for gene: ESR2 were changed from 46,XY Disorders of Sex Development to 46,XY Disorders of Sex Development; Ovarian dysgenesis 8, MIM# 618187
Differences of Sex Development v0.99 ESR2 Zornitza Stark Publications for gene: ESR2 were set to 29261182; 9861029
Differences of Sex Development v0.98 ESR2 Zornitza Stark Classified gene: ESR2 as Amber List (moderate evidence)
Differences of Sex Development v0.98 ESR2 Zornitza Stark Gene: esr2 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.97 ESR2 Zornitza Stark reviewed gene: ESR2: Rating: AMBER; Mode of pathogenicity: None; Publications: 30113650; Phenotypes: Ovarian dysgenesis 8, MIM# 618187; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.97 ERAL1 Zornitza Stark Marked gene: ERAL1 as ready
Differences of Sex Development v0.97 ERAL1 Zornitza Stark Gene: eral1 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.97 ERAL1 Zornitza Stark Classified gene: ERAL1 as Red List (low evidence)
Differences of Sex Development v0.97 ERAL1 Zornitza Stark Gene: eral1 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.96 ERAL1 Zornitza Stark reviewed gene: ERAL1: Rating: RED; Mode of pathogenicity: None; Publications: 28449065; Phenotypes: Perrault syndrome 6, MIM# 617565; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.96 MKKS Zornitza Stark reviewed gene: MKKS: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Bardet-Biedl syndrome 6 (MIM#605231), McKusick-Kaufman syndrome (MIM#236700); Mode of inheritance: None
Differences of Sex Development v0.96 MKKS Zornitza Stark Marked gene: MKKS as ready
Differences of Sex Development v0.96 MKKS Zornitza Stark Gene: mkks has been classified as Red List (Low Evidence).
Differences of Sex Development v0.96 MKKS Zornitza Stark Phenotypes for gene: MKKS were changed from to Bardet-Biedl syndrome 6 (MIM#605231); McKusick-Kaufman syndrome (MIM#236700)
Differences of Sex Development v0.95 MKKS Zornitza Stark Publications for gene: MKKS were set to
Differences of Sex Development v0.94 MKKS Zornitza Stark Mode of inheritance for gene: MKKS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.93 MKKS Zornitza Stark Classified gene: MKKS as Red List (low evidence)
Differences of Sex Development v0.93 MKKS Zornitza Stark Gene: mkks has been classified as Red List (Low Evidence).
Congenital Disorders of Glycosylation v0.89 ST3GAL3 Zornitza Stark Publications for gene: ST3GAL3 were set to
Congenital Disorders of Glycosylation v0.88 CCDC115 Zornitza Stark Marked gene: CCDC115 as ready
Congenital Disorders of Glycosylation v0.88 CCDC115 Zornitza Stark Gene: ccdc115 has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v0.88 CCDC115 Zornitza Stark Classified gene: CCDC115 as Green List (high evidence)
Congenital Disorders of Glycosylation v0.88 CCDC115 Zornitza Stark Gene: ccdc115 has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v0.87 ST3GAL3 Zornitza Stark Mode of inheritance for gene: ST3GAL3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.86 B3GLCT Zornitza Stark Marked gene: B3GLCT as ready
Congenital Disorders of Glycosylation v0.86 B3GLCT Zornitza Stark Gene: b3glct has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v0.86 ST3GAL3 Zornitza Stark Classified gene: ST3GAL3 as Amber List (moderate evidence)
Congenital Disorders of Glycosylation v0.86 ST3GAL3 Zornitza Stark Gene: st3gal3 has been classified as Amber List (Moderate Evidence).
Congenital Disorders of Glycosylation v0.85 B3GLCT Zornitza Stark Classified gene: B3GLCT as Green List (high evidence)
Congenital Disorders of Glycosylation v0.85 B3GLCT Zornitza Stark Gene: b3glct has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v0.84 PAPSS2 Zornitza Stark Marked gene: PAPSS2 as ready
Congenital Disorders of Glycosylation v0.84 PAPSS2 Zornitza Stark Gene: papss2 has been classified as Red List (Low Evidence).
Congenital Disorders of Glycosylation v0.84 TMEM199 Zornitza Stark Marked gene: TMEM199 as ready
Congenital Disorders of Glycosylation v0.84 TMEM199 Zornitza Stark Gene: tmem199 has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v0.84 TMEM199 Zornitza Stark Classified gene: TMEM199 as Green List (high evidence)
Congenital Disorders of Glycosylation v0.84 TMEM199 Zornitza Stark Gene: tmem199 has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v0.83 PAPSS2 Zornitza Stark Phenotypes for gene: PAPSS2 were changed from to Brachyolmia 4 with mild epiphyseal and metaphyseal changes MIM#612847
Congenital Disorders of Glycosylation v0.82 TRIP11 Zornitza Stark Marked gene: TRIP11 as ready
Congenital Disorders of Glycosylation v0.82 TRIP11 Zornitza Stark Gene: trip11 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.92 KISS1R Crystle Lee reviewed gene: KISS1R: Rating: GREEN; Mode of pathogenicity: None; Publications: 17164310, 31073722, 14573733; Phenotypes: Hypogonadotropic hypogonadism 8 with or without anosmia (MIM#614837); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.82 PAPSS2 Zornitza Stark Publications for gene: PAPSS2 were set to
Congenital Disorders of Glycosylation v0.81 PAPSS2 Zornitza Stark Mode of inheritance for gene: PAPSS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.80 CCDC115 Ain Roesley gene: CCDC115 was added
gene: CCDC115 was added to Congenital Disorders of Glycosylation. Sources: Literature
Mode of inheritance for gene: CCDC115 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC115 were set to 26833332
Phenotypes for gene: CCDC115 were set to Congenital disorder of glycosylation, type IIo (MIM# 616828)
Penetrance for gene: CCDC115 were set to unknown
Review for gene: CCDC115 was set to GREEN
Added comment: PMID: 26833332
- 8 affecteds from 5 families. Abnormal N-and mucin type O-glycosylation was found on serum proteins, and reduced metabolic labeling of sialic acids was found in fibroblasts.
Sources: Literature
Congenital Disorders of Glycosylation v0.80 PAPSS2 Zornitza Stark Classified gene: PAPSS2 as Red List (low evidence)
Congenital Disorders of Glycosylation v0.80 PAPSS2 Zornitza Stark Gene: papss2 has been classified as Red List (Low Evidence).
Congenital Disorders of Glycosylation v0.79 TRIP11 Zornitza Stark Mode of inheritance for gene: TRIP11 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.78 ALG2 Zornitza Stark Marked gene: ALG2 as ready
Congenital Disorders of Glycosylation v0.78 ALG2 Zornitza Stark Gene: alg2 has been classified as Red List (Low Evidence).
Congenital Disorders of Glycosylation v0.78 NUS1 Zornitza Stark Mode of inheritance for gene: NUS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.77 NUS1 Zornitza Stark Classified gene: NUS1 as Amber List (moderate evidence)
Congenital Disorders of Glycosylation v0.77 NUS1 Zornitza Stark Gene: nus1 has been classified as Amber List (Moderate Evidence).
Congenital Disorders of Glycosylation v0.76 TRIP11 Zornitza Stark Publications for gene: TRIP11 were set to
Congenital Disorders of Glycosylation v0.76 ALG2 Zornitza Stark Phenotypes for gene: ALG2 were changed from to Congenital disorder of glycosylation, type Ii (MIM# 607906)
Congenital Disorders of Glycosylation v0.75 ALG2 Zornitza Stark Publications for gene: ALG2 were set to
Congenital Disorders of Glycosylation v0.74 TRIP11 Zornitza Stark Classified gene: TRIP11 as Red List (low evidence)
Congenital Disorders of Glycosylation v0.74 TRIP11 Zornitza Stark Gene: trip11 has been classified as Red List (Low Evidence).
Congenital Disorders of Glycosylation v0.73 TRIP11 Zornitza Stark reviewed gene: TRIP11: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Achondrogenesis, type IA MIM# 200600, Osteochondrodysplasia MIM# 184260; Mode of inheritance: None
Congenital Disorders of Glycosylation v0.73 ALG2 Zornitza Stark Mode of inheritance for gene: ALG2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.72 ATP6AP1 Zornitza Stark Marked gene: ATP6AP1 as ready
Congenital Disorders of Glycosylation v0.72 ATP6AP1 Zornitza Stark Gene: atp6ap1 has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v0.72 ATP6AP1 Zornitza Stark Classified gene: ATP6AP1 as Green List (high evidence)
Congenital Disorders of Glycosylation v0.72 ATP6AP1 Zornitza Stark Gene: atp6ap1 has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v0.71 ALG2 Zornitza Stark Classified gene: ALG2 as Red List (low evidence)
Congenital Disorders of Glycosylation v0.71 ALG2 Zornitza Stark Gene: alg2 has been classified as Red List (Low Evidence).
Congenital Disorders of Glycosylation v0.70 TRAPPC11 Zornitza Stark Marked gene: TRAPPC11 as ready
Congenital Disorders of Glycosylation v0.70 TRAPPC11 Zornitza Stark Gene: trappc11 has been classified as Amber List (Moderate Evidence).
Congenital Disorders of Glycosylation v0.70 ST3GAL3 Paul De Fazio changed review comment from: 1 family described with West syndrome (PMID: 23252400). 2 unrelated consanguineous families described in PMID: 21907012. Functional testing supports abnormal enzyme function in all cases but no biochemical studies on patients.

ST3GAL3 located on chr1p34.1 encodes the β-galactoside-α2,3-sialyltransferase-III (ST3Gal-III), which in humans predominantly forms the sialyl Lewis a (sLe a) epitope on glycoproteins.

This gene is on the Invitae and EGL CDG panels.; to: 1 family described with West syndrome (PMID: 23252400). 2 unrelated consanguineous families described in PMID: 21907012 with ID. Functional testing supports abnormal enzyme function in all cases but no biochemical studies on patients.

ST3GAL3 located on chr1p34.1 encodes the β-galactoside-α2,3-sialyltransferase-III (ST3Gal-III), which in humans predominantly forms the sialyl Lewis a (sLe a) epitope on glycoproteins.

This gene is on the Invitae and EGL CDG panels.
Congenital Disorders of Glycosylation v0.70 ST3GAL3 Paul De Fazio reviewed gene: ST3GAL3: Rating: AMBER; Mode of pathogenicity: None; Publications: 23252400, 21907012; Phenotypes: Mental retardation, autosomal recessive 12 MIM# 611090; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Congenital Disorders of Glycosylation v0.70 TRAPPC11 Zornitza Stark Classified gene: TRAPPC11 as Amber List (moderate evidence)
Congenital Disorders of Glycosylation v0.70 TRAPPC11 Zornitza Stark Gene: trappc11 has been classified as Amber List (Moderate Evidence).
Congenital Disorders of Glycosylation v0.69 XYLT2 Zornitza Stark Marked gene: XYLT2 as ready
Congenital Disorders of Glycosylation v0.69 XYLT2 Zornitza Stark Gene: xylt2 has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v0.69 TRAPPC11 Zornitza Stark reviewed gene: TRAPPC11: Rating: AMBER; Mode of pathogenicity: None; Publications: 23830518, 26322222, 29855340, 30105108, 26912795, 27707803, 27862579, 28484880; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 18 MIM# 615356; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.69 XYLT2 Zornitza Stark Phenotypes for gene: XYLT2 were changed from to Spondyloocular syndrome MIM# 605822
Congenital Disorders of Glycosylation v0.68 XYLT2 Zornitza Stark Classified gene: XYLT2 as Green List (high evidence)
Congenital Disorders of Glycosylation v0.68 XYLT2 Zornitza Stark Gene: xylt2 has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v0.67 ALG13 Zornitza Stark Marked gene: ALG13 as ready
Congenital Disorders of Glycosylation v0.67 ALG13 Zornitza Stark Gene: alg13 has been classified as Amber List (Moderate Evidence).
Congenital Disorders of Glycosylation v0.67 ALG13 Zornitza Stark Phenotypes for gene: ALG13 were changed from to Congenital disorder of glycosylation, type Is (MIM# 300884)
Congenital Disorders of Glycosylation v0.66 PIGW Zornitza Stark Marked gene: PIGW as ready
Congenital Disorders of Glycosylation v0.66 PIGW Zornitza Stark Gene: pigw has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v0.66 PIGW Zornitza Stark Phenotypes for gene: PIGW were changed from to Glycosylphosphatidylinositol biosynthesis defect 11, MIM# 616025; intractable seizures; West syndrome; severe developmental delay; dysmorphic facial features; hyperphosphatasia; epilepsy; recurrent respiratory infections; hypotonia; stereotypies
Congenital Disorders of Glycosylation v0.65 PIGW Zornitza Stark Publications for gene: PIGW were set to
Congenital Disorders of Glycosylation v0.64 PIGW Zornitza Stark Mode of inheritance for gene: PIGW was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.63 ALG13 Zornitza Stark Publications for gene: ALG13 were set to 22492991; 28887793; 26138355
Congenital Disorders of Glycosylation v0.62 PIGM Zornitza Stark Marked gene: PIGM as ready
Congenital Disorders of Glycosylation v0.62 PIGM Zornitza Stark Gene: pigm has been classified as Amber List (Moderate Evidence).
Congenital Disorders of Glycosylation v0.62 PIGM Zornitza Stark Tag founder tag was added to gene: PIGM.
Mendeliome v0.3342 PIGM Paul De Fazio reviewed gene: PIGM: Rating: AMBER; Mode of pathogenicity: None; Publications: 31445883, 16767100; Phenotypes: portal vein thrombosis, persistent absence seizures, macrocephaly, infantile-onset cerebrovascular thrombotic events; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Congenital Disorders of Glycosylation v0.62 PIGM Zornitza Stark Phenotypes for gene: PIGM were changed from to portal vein thrombosis; persistent absence seizures; macrocephaly; infantile-onset cerebrovascular thrombotic events
Congenital Disorders of Glycosylation v0.62 ALG13 Zornitza Stark Publications for gene: ALG13 were set to
Congenital Disorders of Glycosylation v0.61 PIGM Zornitza Stark Publications for gene: PIGM were set to
Congenital Disorders of Glycosylation v0.60 ALG13 Zornitza Stark Mode of inheritance for gene: ALG13 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Congenital Disorders of Glycosylation v0.60 PIGM Zornitza Stark Mode of inheritance for gene: PIGM was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.59 PIGM Zornitza Stark Classified gene: PIGM as Amber List (moderate evidence)
Congenital Disorders of Glycosylation v0.59 PIGM Zornitza Stark Gene: pigm has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3342 LEP Crystle Lee reviewed gene: LEP: Rating: GREEN; Mode of pathogenicity: None; Publications: 26567097; Phenotypes: Obesity, morbid, due to leptin deficiency (MIM#614962); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.58 ALG13 Zornitza Stark Classified gene: ALG13 as Amber List (moderate evidence)
Congenital Disorders of Glycosylation v0.58 ALG13 Zornitza Stark Gene: alg13 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.92 LEP Crystle Lee reviewed gene: LEP: Rating: GREEN; Mode of pathogenicity: None; Publications: 26567097, 31483094; Phenotypes: Obesity, morbid, due to leptin deficiency (MIM#614962); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3342 DMRT1 Zornitza Stark Marked gene: DMRT1 as ready
Mendeliome v0.3342 DMRT1 Zornitza Stark Gene: dmrt1 has been classified as Red List (Low Evidence).
Mendeliome v0.3342 DMRT1 Zornitza Stark Phenotypes for gene: DMRT1 were changed from to Azoospermia
Mendeliome v0.3341 DMRT1 Zornitza Stark Publications for gene: DMRT1 were set to
Mendeliome v0.3340 DMRT1 Zornitza Stark Mode of inheritance for gene: DMRT1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3339 DMRT1 Zornitza Stark Classified gene: DMRT1 as Red List (low evidence)
Mendeliome v0.3339 DMRT1 Zornitza Stark Gene: dmrt1 has been classified as Red List (Low Evidence).
Mendeliome v0.3338 DMRT1 Zornitza Stark reviewed gene: DMRT1: Rating: RED; Mode of pathogenicity: None; Publications: 31479588, 24934491, 29527098; Phenotypes: Azoospermia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.92 DMRT1 Zornitza Stark Marked gene: DMRT1 as ready
Differences of Sex Development v0.92 DMRT1 Zornitza Stark Gene: dmrt1 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.92 DMRT1 Zornitza Stark Classified gene: DMRT1 as Red List (low evidence)
Differences of Sex Development v0.92 DMRT1 Zornitza Stark Gene: dmrt1 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.91 DHCR24 Zornitza Stark Marked gene: DHCR24 as ready
Differences of Sex Development v0.91 DHCR24 Zornitza Stark Gene: dhcr24 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.91 DHCR24 Zornitza Stark Phenotypes for gene: DHCR24 were changed from to Desmosterolosis, MIM# 602398
Differences of Sex Development v0.90 DHCR24 Zornitza Stark Publications for gene: DHCR24 were set to
Differences of Sex Development v0.89 DHCR24 Zornitza Stark Mode of inheritance for gene: DHCR24 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.88 DHCR24 Zornitza Stark Classified gene: DHCR24 as Red List (low evidence)
Differences of Sex Development v0.88 DHCR24 Zornitza Stark Gene: dhcr24 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2770 LHX3 Zornitza Stark Marked gene: LHX3 as ready
Intellectual disability syndromic and non-syndromic v0.2770 LHX3 Zornitza Stark Gene: lhx3 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2770 LHX3 Zornitza Stark Phenotypes for gene: LHX3 were changed from to Pituitary hormone deficiency, combined, 3 (MIM#221750)
Intellectual disability syndromic and non-syndromic v0.2769 LHX3 Zornitza Stark Publications for gene: LHX3 were set to
Intellectual disability syndromic and non-syndromic v0.2768 LHX3 Zornitza Stark Mode of inheritance for gene: LHX3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2767 LHX3 Zornitza Stark Classified gene: LHX3 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.2767 LHX3 Zornitza Stark Gene: lhx3 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.87 CYB5A Zornitza Stark Marked gene: CYB5A as ready
Differences of Sex Development v0.87 CYB5A Zornitza Stark Gene: cyb5a has been classified as Green List (High Evidence).
Differences of Sex Development v0.87 CYB5A Zornitza Stark Phenotypes for gene: CYB5A were changed from Methemoglobinemia and ambiguous genitalia 250790 to Methemoglobinemia and ambiguous genitalia, MIM# 250790
Differences of Sex Development v0.86 CYB5A Zornitza Stark Classified gene: CYB5A as Green List (high evidence)
Differences of Sex Development v0.86 CYB5A Zornitza Stark Gene: cyb5a has been classified as Green List (High Evidence).
Differences of Sex Development v0.85 LHX3 Zornitza Stark Marked gene: LHX3 as ready
Differences of Sex Development v0.85 LHX3 Zornitza Stark Gene: lhx3 has been classified as Green List (High Evidence).
Differences of Sex Development v0.85 LHX3 Zornitza Stark Mode of inheritance for gene: LHX3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.84 LHX3 Zornitza Stark Phenotypes for gene: LHX3 were changed from to Pituitary hormone deficiency, combined, 3 (MIM#221750)
Differences of Sex Development v0.83 LHX3 Zornitza Stark Publications for gene: LHX3 were set to
Congenital Disorders of Glycosylation v0.57 B3GLCT Ain Roesley gene: B3GLCT was added
gene: B3GLCT was added to Congenital Disorders of Glycosylation. Sources: Literature
Mode of inheritance for gene: B3GLCT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: B3GLCT were set to 18199743; 16909395
Phenotypes for gene: B3GLCT were set to Peters-plus syndrome (MIM# 261540)
Penetrance for gene: B3GLCT were set to unknown
Review for gene: B3GLCT was set to GREEN
Added comment: PMID: 18199743
- 4 affecteds including 1 pair of siblings with mass spec analysis from patients' serum showing defective O-glycosylation

PMID: 16909395
- 20 affecteds from 15 families with no defective N-glycosylation however authors did not examine O-glycosylation and concluded that absence of defective glycosylation cannot be completely ruled out
Sources: Literature
Differences of Sex Development v0.82 CUL4B Zornitza Stark Marked gene: CUL4B as ready
Differences of Sex Development v0.82 CUL4B Zornitza Stark Gene: cul4b has been classified as Green List (High Evidence).
Differences of Sex Development v0.82 CUL4B Zornitza Stark Mode of inheritance for gene: CUL4B was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Differences of Sex Development v0.81 CUL4B Zornitza Stark Classified gene: CUL4B as Green List (high evidence)
Differences of Sex Development v0.81 CUL4B Zornitza Stark Gene: cul4b has been classified as Green List (High Evidence).
Mendeliome v0.3338 CBX2 Zornitza Stark Marked gene: CBX2 as ready
Mendeliome v0.3338 CBX2 Zornitza Stark Gene: cbx2 has been classified as Red List (Low Evidence).
Mendeliome v0.3338 CBX2 Zornitza Stark Phenotypes for gene: CBX2 were changed from to 46XY sex reversal 5, MIM# 613080
Mendeliome v0.3337 CBX2 Zornitza Stark Publications for gene: CBX2 were set to
Mendeliome v0.3336 CBX2 Zornitza Stark Mode of inheritance for gene: CBX2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3335 CBX2 Zornitza Stark Classified gene: CBX2 as Red List (low evidence)
Mendeliome v0.3335 CBX2 Zornitza Stark Gene: cbx2 has been classified as Red List (Low Evidence).
Mendeliome v0.3334 CBX2 Zornitza Stark reviewed gene: CBX2: Rating: RED; Mode of pathogenicity: None; Publications: 19361780, 31719618, 23219007; Phenotypes: 46XY sex reversal 5, MIM# 613080; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.80 CBX2 Zornitza Stark Marked gene: CBX2 as ready
Differences of Sex Development v0.80 CBX2 Zornitza Stark Gene: cbx2 has been classified as Red List (Low Evidence).
Mendeliome v0.3334 LEPR Crystle Lee reviewed gene: LEPR: Rating: GREEN; Mode of pathogenicity: None; Publications: 17229951, 29545012; Phenotypes: Obesity, morbid, due to leptin receptor deficiency (MIM#614963); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.80 CBX2 Zornitza Stark Phenotypes for gene: CBX2 were changed from to 46XY sex reversal 5, MIM# 613080
Differences of Sex Development v0.79 CBX2 Zornitza Stark Mode of inheritance for gene: CBX2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.78 CBX2 Zornitza Stark Publications for gene: CBX2 were set to
Differences of Sex Development v0.77 CBX2 Zornitza Stark Classified gene: CBX2 as Red List (low evidence)
Differences of Sex Development v0.77 CBX2 Zornitza Stark Gene: cbx2 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.76 LEPR Crystle Lee reviewed gene: LEPR: Rating: GREEN; Mode of pathogenicity: None; Publications: 17229951, 29545012; Phenotypes: Obesity, morbid, due to leptin receptor deficiency (MIM#614963); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.76 CBX2 Zornitza Stark reviewed gene: CBX2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: 46XY sex reversal 5, MIM# 613080; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.76 MCM5 Zornitza Stark Marked gene: MCM5 as ready
Differences of Sex Development v0.76 MCM5 Zornitza Stark Gene: mcm5 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.76 MCM5 Zornitza Stark Phenotypes for gene: MCM5 were changed from Meier-Gorlin syndrome 8 (MIM#617564) to Meier-Gorlin syndrome 8 (MIM#617564)
Differences of Sex Development v0.75 MCM5 Zornitza Stark Phenotypes for gene: MCM5 were changed from Meier-Gorlin syndrome 8 (MIM#617564) to Meier-Gorlin syndrome 8 (MIM#617564)
Differences of Sex Development v0.75 MCM5 Zornitza Stark Phenotypes for gene: MCM5 were changed from ?Meier-Gorlin syndrome 8 (MIM#617564) to Meier-Gorlin syndrome 8 (MIM#617564)
Differences of Sex Development v0.74 MCM5 Zornitza Stark Classified gene: MCM5 as Red List (low evidence)
Differences of Sex Development v0.74 MCM5 Zornitza Stark Gene: mcm5 has been classified as Red List (Low Evidence).
Mendeliome v0.3334 MCM5 Zornitza Stark Marked gene: MCM5 as ready
Mendeliome v0.3334 MCM5 Zornitza Stark Gene: mcm5 has been classified as Red List (Low Evidence).
Mendeliome v0.3334 MCM5 Zornitza Stark Phenotypes for gene: MCM5 were changed from Meier-Gorlin syndrome 8 (MIM#617564) to Meier-Gorlin syndrome 8 (MIM#617564)
Mendeliome v0.3334 MCM5 Zornitza Stark Phenotypes for gene: MCM5 were changed from ?Meier-Gorlin syndrome 8 (MIM#617564) to Meier-Gorlin syndrome 8 (MIM#617564)
Mendeliome v0.3333 MCM5 Zornitza Stark Classified gene: MCM5 as Red List (low evidence)
Mendeliome v0.3333 MCM5 Zornitza Stark Gene: mcm5 has been classified as Red List (Low Evidence).
Skeletal dysplasia v0.35 MCM5 Zornitza Stark Marked gene: MCM5 as ready
Skeletal dysplasia v0.35 MCM5 Zornitza Stark Gene: mcm5 has been classified as Red List (Low Evidence).
Skeletal dysplasia v0.35 MCM5 Zornitza Stark Phenotypes for gene: MCM5 were changed from Meier-Gorlin syndrome 8, MIM# 617564 to Meier-Gorlin syndrome 8, MIM# 617564
Skeletal dysplasia v0.35 MCM5 Zornitza Stark Phenotypes for gene: MCM5 were changed from ?Meier-Gorlin syndrome 8 617564 to Meier-Gorlin syndrome 8, MIM# 617564
Mendeliome v0.3332 ATF3 Zornitza Stark Marked gene: ATF3 as ready
Mendeliome v0.3332 ATF3 Zornitza Stark Gene: atf3 has been classified as Red List (Low Evidence).
Mendeliome v0.3332 ATF3 Zornitza Stark Classified gene: ATF3 as Red List (low evidence)
Mendeliome v0.3332 ATF3 Zornitza Stark Gene: atf3 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.73 ATF3 Zornitza Stark Marked gene: ATF3 as ready
Differences of Sex Development v0.73 ATF3 Zornitza Stark Gene: atf3 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.73 ATF3 Zornitza Stark Classified gene: ATF3 as Red List (low evidence)
Differences of Sex Development v0.73 ATF3 Zornitza Stark Gene: atf3 has been classified as Red List (Low Evidence).
Bardet Biedl syndrome v0.31 MKKS Zornitza Stark Marked gene: MKKS as ready
Bardet Biedl syndrome v0.31 MKKS Zornitza Stark Gene: mkks has been classified as Green List (High Evidence).
Bardet Biedl syndrome v0.31 MKKS Zornitza Stark Phenotypes for gene: MKKS were changed from to Bardet-Biedl syndrome 6 (MIM#605231)
Bardet Biedl syndrome v0.30 MKKS Zornitza Stark Publications for gene: MKKS were set to
Bardet Biedl syndrome v0.29 MKKS Zornitza Stark Mode of inheritance for gene: MKKS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.72 LHB Crystle Lee reviewed gene: LHB: Rating: GREEN; Mode of pathogenicity: None; Publications: 17761593, 28092701, 29476300, 22723313, 15602022; Phenotypes: Hypogonadotropic hypogonadism 23 with or without anosmia (MIM#228300); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.72 FEZF1 Elena Savva reviewed gene: FEZF1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 25192046, 32400067; Phenotypes: Hypogonadotropic hypogonadism 22, with or without anosmia 616030; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3331 FEZF1 Elena Savva reviewed gene: FEZF1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 25192046, 32400067; Phenotypes: Hypogonadotropic hypogonadism 22, with or without anosmia 616030; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.57 TMEM199 Paul De Fazio gene: TMEM199 was added
gene: TMEM199 was added to Congenital Disorders of Glycosylation. Sources: Literature
Mode of inheritance for gene: TMEM199 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM199 were set to 26833330; 29321044
Phenotypes for gene: TMEM199 were set to Congenital disorder of glycosylation, type IIp MIM# 616829
Review for gene: TMEM199 was set to GREEN
gene: TMEM199 was marked as current diagnostic
Added comment: 4 patients from 3 unrelated families with a mild metabolic disorder primarily affecting the liver (PMID: 26833330). All patients had a type 2 pattern on serum transferrin isoelectric focusing (IEF), indicating abnormal N-glycosylation, as well as abnormal IEF of ApoC-III, indicating abnormal O-glycosylation.

A follow up publication described 3 more unrelated cases with protein glycosylation deficiency, supporting the original paper (PMID: 29321044).

Although this gene is red on PanelApp UK it has 2 green reviews (and no others).
Sources: Literature
Congenital Disorders of Glycosylation v0.57 PAPSS2 Naomi Baker reviewed gene: PAPSS2: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 22791835, 25594860, 31461705, 23633440, 9771708, 19474428.; Phenotypes: Brachyolmia 4 with mild epiphyseal and metaphyseal changes MIM#612847; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.57 NUS1 Belinda Chong reviewed gene: NUS1: Rating: AMBER; Mode of pathogenicity: None; Publications: 610463, 25066056; Phenotypes: Congenital disorder of glycosylation, type 1aa; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.57 TRIP11 Paul De Fazio reviewed gene: TRIP11: Rating: AMBER; Mode of pathogenicity: None; Publications: 29872333, 20089971, 30728324, 30518689; Phenotypes: Achondrogenesis, type IA MIM# 200600, Osteochondrodysplasia MIM# 184260; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Differences of Sex Development v0.72 ERAL1 Elena Savva gene: ERAL1 was added
gene: ERAL1 was added to Disorders of Sex Differentiation. Sources: Expert list
Mode of inheritance for gene: ERAL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERAL1 were set to PMID: 28449065
Phenotypes for gene: ERAL1 were set to Perrault syndrome 6 617565
Review for gene: ERAL1 was set to AMBER
Added comment: PMID: 28449065 - 3 unrelated patient with perrault syndrome with the same founder missense (p.Asn236Ile). Symptoms included hearing loss, premature ovarian failure, primary amenorrhea
Supported by functional analysis on patient cells, and transfected yeast reciprocating the phenotype.
Sources: Expert list
Congenital Disorders of Glycosylation v0.57 ATP6AP1 Ain Roesley gene: ATP6AP1 was added
gene: ATP6AP1 was added to Congenital Disorders of Glycosylation. Sources: Literature
Mode of inheritance for gene: ATP6AP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP6AP1 were set to PMID: 27231034
Phenotypes for gene: ATP6AP1 were set to immunodeficiency-47 (MIM# 300972)
Penetrance for gene: ATP6AP1 were set to unknown
Review for gene: ATP6AP1 was set to GREEN
Added comment: PMID: 27231034
- 11 males from 6 families with defective glycosylation
Sources: Literature
Differences of Sex Development v0.72 DMRT1 Elena Savva gene: DMRT1 was added
gene: DMRT1 was added to Disorders of Sex Differentiation. Sources: Expert list
Mode of inheritance for gene: DMRT1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DMRT1 were set to PMID: 31479588; 24934491; 29527098
Phenotypes for gene: DMRT1 were set to Azoospermia
Review for gene: DMRT1 was set to RED
Added comment: PMID: 31479588 - 1 patient with azoospermia and XY genotype. Also carries an additional variant in KLHL10

PMID: 24934491 - 6 patients with male infertility, however the 4 identified variants were also found in 2 controls and have a high frequency in the population (gnomAD). No functional studies.

PMID: 23555275 - Identifies CNVs in azoospermia patients, calls the gene a risk factor
Sources: Expert list
Congenital Disorders of Glycosylation v0.57 ALG2 Ain Roesley reviewed gene: ALG2: Rating: RED; Mode of pathogenicity: None; Publications: 12684507, 23404334, 24461433; Phenotypes: Congenital disorder of glycosylation, type Ii (MIM# 607906); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.72 DHCR24 Elena Savva reviewed gene: DHCR24: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 9450875, 11519011; Phenotypes: Desmosterolosis 602398; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Gastrointestinal neuromuscular disease v0.28 POLG2 Bryony Thompson Marked gene: POLG2 as ready
Gastrointestinal neuromuscular disease v0.28 POLG2 Bryony Thompson Gene: polg2 has been classified as Red List (Low Evidence).
Gastrointestinal neuromuscular disease v0.28 POLG2 Bryony Thompson gene: POLG2 was added
gene: POLG2 was added to Gastrointestinal neuromuscular disease. Sources: Expert list
Mode of inheritance for gene: POLG2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POLG2 were set to 21555342; 27775730
Phenotypes for gene: POLG2 were set to Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4 MIM#610131
Review for gene: POLG2 was set to RED
Added comment: 3 unrelated cases have been reported with gastrointestinal symptoms and 3 different heterozygous missense (L153V, R369G, S423Y). All 3 missense are too common in gnomAD v2.1 for a dominant disease and biochemical assays demonstrated normal function for all expect R369G variants had reduced stimulation of processivity and decreased affinity for the catalytic subunit.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2766 LHX3 Crystle Lee reviewed gene: LHX3: Rating: RED; Mode of pathogenicity: None; Publications: 28302169; Phenotypes: Pituitary hormone deficiency, combined, 3 (MIM#221750); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.72 CYB5A Elena Savva gene: CYB5A was added
gene: CYB5A was added to Disorders of Sex Differentiation. Sources: Expert list
Mode of inheritance for gene: CYB5A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYB5A were set to PMID: 22170710; 32051920
Phenotypes for gene: CYB5A were set to Methemoglobinemia and ambiguous genitalia 250790
Review for gene: CYB5A was set to GREEN
Added comment: PMID: 22170710 - 3 siblings with 46,XY DSD, sex steroid deficiency, female genitalia and a homozygous missense variant. Supported by LOF functional studies. Mineralocorticoids and glucocorticoids were normal.

PMID: 32051920 - 1 female with a homozygous missense, no DSD but methemoglobinemia. All female genitalia are normal and she has had a normal female child.
Paper reviews prior reports and notes an additional 2 unrelated homozygous reports of 46 XY DSD patients with normal Methemoglobin. All variants were rare/absent (gnomAD) and PTCs.
Sources: Expert list
Differences of Sex Development v0.72 LHX3 Crystle Lee reviewed gene: LHX3: Rating: GREEN; Mode of pathogenicity: None; Publications: 28302169, 17327381, 30262920; Phenotypes: Pituitary hormone deficiency, combined, 3 (MIM#221750); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.72 CUL4B Elena Savva gene: CUL4B was added
gene: CUL4B was added to Disorders of Sex Differentiation. Sources: Expert list
Mode of inheritance for gene: CUL4B was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: CUL4B were set to PMID: 25385192
Phenotypes for gene: CUL4B were set to Mental retardation, X-linked, syndromic 15 (Cabezas type) 300354
Review for gene: CUL4B was set to GREEN
Added comment: PMID: 25385192 - 25 patients (11 families) with syndromic features including hypogonadism (85%) and gynecomastia (33%)
Sources: Expert list
Congenital Disorders of Glycosylation v0.57 TRAPPC11 Paul De Fazio changed review comment from: Association with a multisystem disorder including muscular dystrophy is established (green in our Muscular dystrophy gene list).

Biochemical studies in zebrafish show that TRAPPC11 is involved in protein glycosylation (PMID: 26912795). The authors proposed that TRAPPC11 may function as a scaffold for enzymes of protein N-glycosylation or as a cofactor for an enzyme in lipid-linked oligosaccharide synthesis.

Patients with homozygous or compound heterozygous TRAPPC11 variants have been found to have abnormal glycosylation of the LAMP1/LAMP2 proteins (PMID: 23830518, 27707803). TRAPPC11 has been implicated in α-dystroglycan hypoglycosylation (PMID: 29855340).

A patient with biallelic TRAPPC11 variants was found to have abnormal transferrin and Apo CIII glycosylation patterns, consistent with a CDG (PMID: 27862579).

TRAPPC11-CDG has been suggested to be a "Novel CDG in ER to Golgi trafficking
" (PMID: 28484880)
Sources: Literature; to: Association with a multisystem disorder including muscular dystrophy is established (green in our Muscular dystrophy gene list).

Biochemical studies in zebrafish show that TRAPPC11 is involved in protein glycosylation (PMID: 26912795). The authors proposed that TRAPPC11 may function as a scaffold for enzymes of protein N-glycosylation or as a cofactor for an enzyme in lipid-linked oligosaccharide synthesis.

Patients with homozygous or compound heterozygous TRAPPC11 variants have been found to have abnormal glycosylation of the LAMP1/LAMP2 proteins (PMID: 23830518, 27707803). TRAPPC11 has been implicated in α-dystroglycan hypoglycosylation (PMID: 29855340).

A patient with biallelic TRAPPC11 variants was found to have abnormal transferrin and Apo CIII glycosylation patterns, consistent with a CDG (PMID: 27862579).

TRAPPC11-CDG has been suggested to be a "Novel CDG in ER to Golgi trafficking" (PMID: 28484880)
Sources: Literature
Congenital Disorders of Glycosylation v0.57 TRAPPC11 Paul De Fazio gene: TRAPPC11 was added
gene: TRAPPC11 was added to Congenital Disorders of Glycosylation. Sources: Literature
Mode of inheritance for gene: TRAPPC11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRAPPC11 were set to 23830518; 26322222; 29855340; 30105108; 26912795; 27707803; 27862579; 28484880
Phenotypes for gene: TRAPPC11 were set to Muscular dystrophy, limb-girdle, autosomal recessive 18 MIM# 615356
Review for gene: TRAPPC11 was set to GREEN
gene: TRAPPC11 was marked as current diagnostic
Added comment: Association with a multisystem disorder including muscular dystrophy is established (green in our Muscular dystrophy gene list).

Biochemical studies in zebrafish show that TRAPPC11 is involved in protein glycosylation (PMID: 26912795). The authors proposed that TRAPPC11 may function as a scaffold for enzymes of protein N-glycosylation or as a cofactor for an enzyme in lipid-linked oligosaccharide synthesis.

Patients with homozygous or compound heterozygous TRAPPC11 variants have been found to have abnormal glycosylation of the LAMP1/LAMP2 proteins (PMID: 23830518, 27707803). TRAPPC11 has been implicated in α-dystroglycan hypoglycosylation (PMID: 29855340).

A patient with biallelic TRAPPC11 variants was found to have abnormal transferrin and Apo CIII glycosylation patterns, consistent with a CDG (PMID: 27862579).

TRAPPC11-CDG has been suggested to be a "Novel CDG in ER to Golgi trafficking
" (PMID: 28484880)
Sources: Literature
Differences of Sex Development v0.72 NR3C1 Zornitza Stark Marked gene: NR3C1 as ready
Differences of Sex Development v0.72 NR3C1 Zornitza Stark Gene: nr3c1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.72 NR3C1 Zornitza Stark Phenotypes for gene: NR3C1 were changed from to Glucocorticoid resistance (MIM#615962)
Differences of Sex Development v0.71 NR3C1 Zornitza Stark Publications for gene: NR3C1 were set to
Differences of Sex Development v0.70 NR3C1 Zornitza Stark Mode of inheritance for gene: NR3C1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.69 CBX2 Elena Savva reviewed gene: CBX2: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 19361780, 31719618, 23219007; Phenotypes: ?46XY sex reversal 5 613080; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.69 MCM5 Crystle Lee gene: MCM5 was added
gene: MCM5 was added to Disorders of Sex Differentiation. Sources: Expert Review
Mode of inheritance for gene: MCM5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MCM5 were set to 28198391
Phenotypes for gene: MCM5 were set to ?Meier-Gorlin syndrome 8 (MIM#617564)
Review for gene: MCM5 was set to RED
Added comment: Only single patient reported in 2017. Patient presented with microstomia, thick lips, micrognathia, bilateral microtia, low set ears and bilateral cryptorchidism.
Sources: Expert Review
Mendeliome v0.3331 MCM5 Crystle Lee gene: MCM5 was added
gene: MCM5 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: MCM5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MCM5 were set to 28198391
Phenotypes for gene: MCM5 were set to ?Meier-Gorlin syndrome 8 (MIM#617564)
Review for gene: MCM5 was set to RED
Added comment: Compound heterozgyous variants reported in one patient. Insufficient evidence supporting gene disease association
Sources: Expert Review
Congenital Disorders of Glycosylation v0.57 XYLT2 Paul De Fazio edited their review of gene: XYLT2: Changed phenotypes: Spondyloocular syndrome MIM# 605822
Skeletal dysplasia v0.34 MCM5 Crystle Lee reviewed gene: MCM5: Rating: RED; Mode of pathogenicity: None; Publications: 28198391; Phenotypes: ?Meier-Gorlin syndrome 8 (MIM#617564); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.57 XYLT2 Paul De Fazio gene: XYLT2 was added
gene: XYLT2 was added to Congenital Disorders of Glycosylation. Sources: Literature
Mode of inheritance for gene: XYLT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: XYLT2 were set to 26027496; 26987875; 30891060; 28484880
Review for gene: XYLT2 was set to GREEN
gene: XYLT2 was marked as current diagnostic
Added comment: 5 unrelated individuals/families in total described with Spondylo-Ocular Syndrome (PMID: 26027496, 26987875, 30891060).

XYLT2-CDG has been referred to as a "proteoglycan ‘linker’ glycan disorder" (PMID: 28484880)
Sources: Literature
Differences of Sex Development v0.69 MKKS Crystle Lee reviewed gene: MKKS: Rating: AMBER; Mode of pathogenicity: None; Publications: 10973251, 26900326, 10973238; Phenotypes: Bardet-Biedl syndrome 6 (MIM#605231), McKusick-Kaufman syndrome (MIM#236700); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.57 PIGW Dean Phelan changed review comment from: OMIM - Glycosylphosphatidylinositol biosynthesis defect 11, AR

Function - Glycosylphosphatidylinositol (GPI) is a complex glycolipid that anchors many proteins to the cell surface. PIGW acts in the third step of GPI biosynthesis and acylates the inositol ring of phosphatidylinositol

Clingen - no association with CGD

PMID: 24367057 - (2013) - A patient born to non-consanguineous parents developed intractable seizures with typical hypsarrhythmic pattern in electroencephalography, and was diagnosed as having West syndrome. Because the patient showed severe developmental delay with dysmorphic facial features and hyperphosphatasia, characteristics often seen in IGDs, the patient was tested for GPI deficiency. The patient had decreased surface expression of GPI-APs on blood granulocytes and was identified to be compound heterozygous for NM_178517:c.211A>C and c.499A>G mutations in PIGW.

PMID: 27626616 - (2016) Two second-degree cousins with unexplained patterns of seizures. Next-generation sequencing identified the homozygous c.460A>G; p.(R154G) PIGW mutation in both patients. Transfection of the mutated allele into Pigw-defective CHO cells indicated impaired enzymatic activity of the mutated PIGW product. The patients' phenotype is remarkably different from the phenotype of the only other described individual with PIGW mutations.

PMID: 30813920 - (2019) A Chinese boy with compound heterozygous PIGW mutations who suffers from severe pneumonia, mental retardation, and epilepsy. A 70-day-old boy presented with fever and cough over 20 days in duration at the time of admission. At the age of 6 months, unusual facial features were apparent, and seizures were clinically observed, accompanied by obvious cognitive delay. Next-generation sequencing identified novel PIGW c.178G > A and c.462A > T mutations

PMID: 32198969 - (2020) A new patient with a novel homozygous missense variant in PIGW, who presented with hypotonia, severe intellectual disability, early-onset epileptic seizures, brain abnormalities, nystagmus, hand stereotypies, recurrent respiratory infections, distinctive facial features, and hyperphosphatasia. Our report expands the phenotype of GPI biosynthesis defect 11 to include stereotypies and recurrent respiratory infections.; to: OMIM - Glycosylphosphatidylinositol biosynthesis defect 11, AR

Function - Glycosylphosphatidylinositol (GPI) is a complex glycolipid that anchors many proteins to the cell surface. PIGW acts in the third step of GPI biosynthesis and acylates the inositol ring of phosphatidylinositol

Clingen - no association with CGD

PMID: 24367057 - (2013) - A patient born to non-consanguineous parents developed intractable seizures with typical hypsarrhythmic pattern in electroencephalography, and was diagnosed as having West syndrome. Because the patient showed severe developmental delay with dysmorphic facial features and hyperphosphatasia, characteristics often seen in IGDs, the patient was tested for GPI deficiency. The patient had decreased surface expression of GPI-APs on blood granulocytes and was identified to be compound heterozygous for NM_178517:c.211A>C and c.499A>G mutations in PIGW.

PMID: 27626616 - (2016) Two second-degree cousins with unexplained patterns of seizures. Next-generation sequencing identified the homozygous c.460A>G; p.(R154G) PIGW mutation in both patients. Transfection of the mutated allele into Pigw-defective CHO cells indicated impaired enzymatic activity of the mutated PIGW product. The patients' phenotype is remarkably different from the phenotype of the only other described individual with PIGW mutations.

PMID: 30813920 - (2019) A Chinese boy with compound heterozygous PIGW mutations who suffers from severe pneumonia, mental retardation, and epilepsy. A 70-day-old boy presented with fever and cough over 20 days in duration at the time of admission. At the age of 6 months, unusual facial features were apparent, and seizures were clinically observed, accompanied by obvious cognitive delay. Next-generation sequencing identified novel PIGW c.178G > A and c.462A > T mutations

PMID: 32198969 - (2020) A new patient with a novel homozygous missense variant in PIGW, who presented with hypotonia, severe intellectual disability, early-onset epileptic seizures, brain abnormalities, nystagmus, hand stereotypies, recurrent respiratory infections, distinctive facial features, and hyperphosphatasia. Our report expands the phenotype of GPI biosynthesis defect 11 to include stereotypies and recurrent respiratory infections.

Summary - Multiple unrelated families reported with different recessive variants either homozygous or compound heterozygous. Functional studies showed impaired enzymatic activity
Congenital Disorders of Glycosylation v0.57 PIGW Dean Phelan reviewed gene: PIGW: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 24367057, 27626616, 30813920, 32198969; Phenotypes: intractable seizures, West syndrome, severe developmental delay, dysmorphic facial features, hyperphosphatasia, epilepsy, recurrent respiratory infections, hypotonia, stereotypies; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3331 ATF3 Elena Savva reviewed gene: ATF3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Differences of Sex Development v0.69 ATF3 Elena Savva reviewed gene: ATF3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Bardet Biedl syndrome v0.28 MKKS Crystle Lee reviewed gene: MKKS: Rating: GREEN; Mode of pathogenicity: None; Publications: 10973251; Phenotypes: Bardet-Biedl syndrome 6 (MIM#605231); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.57 PIGM Dean Phelan reviewed gene: PIGM: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 31445883, 16767100; Phenotypes: portal vein thrombosis, persistent absence seizures, macrocephaly, infantile-onset cerebrovascular thrombotic events; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.69 NR3C1 Crystle Lee reviewed gene: NR3C1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30158362; Phenotypes: Glucocorticoid resistance (MIM#615962); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Congenital Disorders of Glycosylation v0.57 ALG13 Ain Roesley reviewed gene: ALG13: Rating: AMBER; Mode of pathogenicity: None; Publications: 22492991, 28887793, 26138355; Phenotypes: Congenital disorder of glycosylation, type Is (MIM# 300884); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.2766 ATL1 Zornitza Stark Marked gene: ATL1 as ready
Intellectual disability syndromic and non-syndromic v0.2766 ATL1 Zornitza Stark Gene: atl1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2766 ATL1 Zornitza Stark Phenotypes for gene: ATL1 were changed from to Neuropathy, hereditary sensory, type ID, MIM# 613708; Spastic paraplegia 3A, autosomal dominant, MIM# 182600
Intellectual disability syndromic and non-syndromic v0.2765 ATL1 Zornitza Stark Publications for gene: ATL1 were set to
Intellectual disability syndromic and non-syndromic v0.2764 ATL1 Zornitza Stark Mode of inheritance for gene: ATL1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2763 ATL1 Zornitza Stark Classified gene: ATL1 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.2763 ATL1 Zornitza Stark Gene: atl1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2762 ATL1 Zornitza Stark reviewed gene: ATL1: Rating: RED; Mode of pathogenicity: None; Publications: 21336785, 28736820, 29180453, 29691679, 31236401; Phenotypes: Neuropathy, hereditary sensory, type ID, MIM# 613708, Spastic paraplegia 3A, autosomal dominant, MIM# 182600; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3331 CNPY3 Zornitza Stark Marked gene: CNPY3 as ready
Mendeliome v0.3331 CNPY3 Zornitza Stark Gene: cnpy3 has been classified as Green List (High Evidence).
Mendeliome v0.3331 CNPY3 Zornitza Stark Phenotypes for gene: CNPY3 were changed from to Epileptic encephalopathy, early infantile, 60 (MIM 617929)
Mendeliome v0.3330 CNPY3 Zornitza Stark Publications for gene: CNPY3 were set to
Mendeliome v0.3329 CNPY3 Zornitza Stark Mode of inheritance for gene: CNPY3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3328 CNPY3 Zornitza Stark reviewed gene: CNPY3: Rating: GREEN; Mode of pathogenicity: None; Publications: 29394991, 30237576; Phenotypes: Epileptic encephalopathy, early infantile, 60 (MIM 617929); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2762 CNPY3 Zornitza Stark Marked gene: CNPY3 as ready
Intellectual disability syndromic and non-syndromic v0.2762 CNPY3 Zornitza Stark Gene: cnpy3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2762 CNPY3 Zornitza Stark Classified gene: CNPY3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2762 CNPY3 Zornitza Stark Gene: cnpy3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.752 CNPY3 Zornitza Stark Marked gene: CNPY3 as ready
Genetic Epilepsy v0.752 CNPY3 Zornitza Stark Gene: cnpy3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.752 CNPY3 Zornitza Stark Phenotypes for gene: CNPY3 were changed from to Epileptic encephalopathy, early infantile, 60 (MIM 617929)
Genetic Epilepsy v0.751 CNPY3 Zornitza Stark Publications for gene: CNPY3 were set to
Genetic Epilepsy v0.750 CNPY3 Zornitza Stark Mode of inheritance for gene: CNPY3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3328 KIF21B Zornitza Stark Marked gene: KIF21B as ready
Mendeliome v0.3328 KIF21B Zornitza Stark Gene: kif21b has been classified as Green List (High Evidence).
Mendeliome v0.3328 KIF21B Zornitza Stark Classified gene: KIF21B as Green List (high evidence)
Mendeliome v0.3328 KIF21B Zornitza Stark Gene: kif21b has been classified as Green List (High Evidence).
Mendeliome v0.3327 KIF21B Zornitza Stark gene: KIF21B was added
gene: KIF21B was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: KIF21B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIF21B were set to 32415109
Phenotypes for gene: KIF21B were set to Global developmental delay; Intellectual disability; Abnormality of brain morphology; Microcephaly
Mode of pathogenicity for gene: KIF21B 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: KIF21B was set to GREEN
Added comment: Asselin et al (2020 - PMID: 32415109) report on 4 individuals with KIF21B pathogenic variants. DD/ID (borderline intellectual functioning to severe ID) was a feature in all. Variable other findings included brain malformations (CCA) and microcephaly. 3 missense variants and a 4-bp insertion were identified, in 3 cases as de novo events while in a single subject the variant was inherited from the father who was also affected. The authors provide evidence for a role of KIF21B in the regulation of processes involved in cortical development and deleterious effect of the missense variants impeding neuronal migration and kinesin autoinhibition. Phenotypes specific to variants (e.g. CCA or microcephaly) were recapitulated in animal models. Missense variants are thought to exert a gain-of-function effect. As commented on, the 4-bp duplication (/frameshift) variant might not be pathogenic. In blood sample from the respective individual, RT-qPCR analysis suggested that haploinsufficiency (NMD) applies. Although Kif21b haploinsufficiency in mice was shown to lead to impaired neuronal positioning, the gene might partially tolerate LoF variants as also suggested by 28 such variants in gnomAD. Homozygous Kif21b ko mice display severe morphological abnormalities, partial loss of commissural fibers, cognitive deficits and altered synaptic transmission (several refs to previous studies provided by the authors).
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.2761 KIF21B Zornitza Stark Marked gene: KIF21B as ready
Intellectual disability syndromic and non-syndromic v0.2761 KIF21B Zornitza Stark Gene: kif21b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2761 KIF21B Zornitza Stark Classified gene: KIF21B as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2761 KIF21B Zornitza Stark Gene: kif21b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2760 PAX1 Zornitza Stark Marked gene: PAX1 as ready
Intellectual disability syndromic and non-syndromic v0.2760 PAX1 Zornitza Stark Gene: pax1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2760 PAX1 Zornitza Stark Classified gene: PAX1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2760 PAX1 Zornitza Stark Gene: pax1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2760 PAX1 Zornitza Stark Classified gene: PAX1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2760 PAX1 Zornitza Stark Gene: pax1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2759 TMEM106B Zornitza Stark Marked gene: TMEM106B as ready
Intellectual disability syndromic and non-syndromic v0.2759 TMEM106B Zornitza Stark Gene: tmem106b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2759 TMEM106B Zornitza Stark Classified gene: TMEM106B as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2759 TMEM106B Zornitza Stark Gene: tmem106b has been classified as Green List (High Evidence).
Genetic Epilepsy v0.749 TMEM106B Zornitza Stark Marked gene: TMEM106B as ready
Genetic Epilepsy v0.749 TMEM106B Zornitza Stark Gene: tmem106b has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.749 TMEM106B Zornitza Stark Classified gene: TMEM106B as Amber List (moderate evidence)
Genetic Epilepsy v0.749 TMEM106B Zornitza Stark Gene: tmem106b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3326 TBC1D2B Zornitza Stark Marked gene: TBC1D2B as ready
Mendeliome v0.3326 TBC1D2B Zornitza Stark Gene: tbc1d2b has been classified as Green List (High Evidence).
Mendeliome v0.3326 TBC1D2B Zornitza Stark Classified gene: TBC1D2B as Green List (high evidence)
Mendeliome v0.3326 TBC1D2B Zornitza Stark Gene: tbc1d2b has been classified as Green List (High Evidence).
Mendeliome v0.3325 TBC1D2B Zornitza Stark gene: TBC1D2B was added
gene: TBC1D2B was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: TBC1D2B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBC1D2B were set to 32623794
Phenotypes for gene: TBC1D2B were set to Global developmental delay; Intellectual disability; Seizures; Gingival overgrowth; Behavioral abnormality; Abnormality of the mandible; Abnormality of brain morphology; Abnormality of the eye; Hearing abnormality
Review for gene: TBC1D2B was set to GREEN
Added comment: Harms et al (2020 - PMID: 32623794) report on 3 unrelated individuals with biallelic pLoF TBC1D2B variants. Features included cognitive impairment (mild ID in one case, regression at the age of 12y in another, hypotonia and delayed milestones in a third aged 8m), seizures (3/3 - variable age of onset) and/or gingival overgrowth (2/3 - prior to initiation of AEDs). Other findings included behavioral abnormalities, mandibular anomalies, abnormal brain imaging and ophthalmologic or (rarely) audiometric evaluations. All were born to non-consanguineous couples and additional investigations were performed in some. Variants were identified by WES or trio WGS, with Sanger confirmation/compatible segregation analyses. In line with the pLoF variants, mRNA studies in fibroblasts from 2 unrelated affected individuals demonstrated significantly reduced (~80-90%) TBC1C2D mRNA levels compared to controls, restored following cycloheximide treatment. Protein was absent in patient fibroblasts. TBC-domain containing GTPase activating proteins are known as key regulators of RAB GTPase activity. TBC1D2B was shown to colocalize with RAB5-positive endocytic vesicles. CRISPR/Cas9-mediated ko of TBC1D2B in HeLa cells suggested a role in EGF receptor endocytosis and decreased cell viability of TBC1D2B-deficient HeLa cells upon serum deprivation. Genes encoding other TBC domain-containg GTPase-activating proteins, e.g. TBC1D7 and TBC1D20, TBC1D24 are associated with recessive neurodevelopmental disorders (with ID and/or seizures) and the pathophysiological defect in TBC1D2B-related disorder (deficit in vesicle trafficking and/or cell survival) is proposed to be similar to that of TBC1D24.
Sources: Expert Review
Genetic Epilepsy v0.748 TBC1D2B Zornitza Stark Classified gene: TBC1D2B as Green List (high evidence)
Genetic Epilepsy v0.748 TBC1D2B Zornitza Stark Gene: tbc1d2b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2758 TBC1D2B Zornitza Stark Marked gene: TBC1D2B as ready
Intellectual disability syndromic and non-syndromic v0.2758 TBC1D2B Zornitza Stark Gene: tbc1d2b has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2758 TBC1D2B Zornitza Stark Classified gene: TBC1D2B as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2758 TBC1D2B Zornitza Stark Gene: tbc1d2b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3324 EXOC2 Zornitza Stark Marked gene: EXOC2 as ready
Mendeliome v0.3324 EXOC2 Zornitza Stark Gene: exoc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3324 EXOC2 Zornitza Stark Classified gene: EXOC2 as Amber List (moderate evidence)
Mendeliome v0.3324 EXOC2 Zornitza Stark Gene: exoc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3323 EXOC2 Zornitza Stark gene: EXOC2 was added
gene: EXOC2 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: EXOC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOC2 were set to 32639540
Phenotypes for gene: EXOC2 were set to Global developmental delay; Intellectual disability; Abnormality of the face; Abnormality of brain morphology
Review for gene: EXOC2 was set to AMBER
Added comment: Van Bergen et al (2020 - PMID: 32639540) report on 3 individuals from 2 families, harboring biallelic EXOC2 mutations. Clinical presentation included DD, ID (severe in 2 subjects from fam1, borderline intellectual functioning in fam2), dysmorphic features and brain abnormalities. Cerebellar anomalies were common to all with a molar tooth sign observed in one (1/3). Other findings limited to subjects from one family included acquired microcephaly, congenital contractures, spastic quadriplegia (each observed 2/3). Previous investigations were in all cases non-diagnostic. WES identified biallelic EXOC2 mutations in all affected individuals. EXOC2 encodes an exocyst subunit. The latter is an octameric complex, component of the membrane transport machinery, required for tethering and fusion of vesicles at the plasma membrane. As discussed ,vesicle transport is important for the development of brain and the function of neurons and glia. Exocyst function is also important for delivery of Arl13b to the primary cilium (biallelic ARL13B mutations cause Joubert syndrome 8) and ciliogenesis. Affected subjects from a broader consanguineous family (fam1) were homozygous for a truncating variant. Fibroblast studies revealed mRNA levels compatible with NMD (further restored in presence of CHX) as well as reduced protein levels. The female belonging to the second non-consanguineous family was found to harbor 2 missense variants in trans configuration. An exocytosis defect was demonstrated in fibroblasts from individuals belonging to both families. Ciliogenesis appeared to be normal, however Arl13b localization/recruitment to the cilia was reduced compared with control cells with the defect rescued upon exogenous expression of wt EXOC2. Mutations in other genes encoding components of the exocyst complex have been previously reported in individuals with relevant phenotypes (e.g. EXOC8 in a boy with features of Joubert s. or EXOC4 in nephrotic syndrome). The authors discuss on the essential role of EXOC2 based on model organism studies (e.g. impaired neuronal membrane traffic, failure of neuronal polarization and neuromuscular junction expansion seen in Drosophila Sec5 (EXOC2) null mutants).
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.2757 EXOC2 Zornitza Stark Marked gene: EXOC2 as ready
Intellectual disability syndromic and non-syndromic v0.2757 EXOC2 Zornitza Stark Gene: exoc2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2757 EXOC2 Zornitza Stark Classified gene: EXOC2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2757 EXOC2 Zornitza Stark Gene: exoc2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2756 CEP120 Zornitza Stark Marked gene: CEP120 as ready
Intellectual disability syndromic and non-syndromic v0.2756 CEP120 Zornitza Stark Gene: cep120 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2756 CEP120 Zornitza Stark Classified gene: CEP120 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2756 CEP120 Zornitza Stark Gene: cep120 has been classified as Green List (High Evidence).
Mendeliome v0.3322 CCDC174 Zornitza Stark Marked gene: CCDC174 as ready
Mendeliome v0.3322 CCDC174 Zornitza Stark Gene: ccdc174 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3322 CCDC174 Zornitza Stark Classified gene: CCDC174 as Amber List (moderate evidence)
Mendeliome v0.3322 CCDC174 Zornitza Stark Gene: ccdc174 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3321 CCDC174 Zornitza Stark gene: CCDC174 was added
gene: CCDC174 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: CCDC174 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC174 were set to 26358778
Phenotypes for gene: CCDC174 were set to Hypotonia, infantile, with psychomotor retardation - IHPMR, 616816
Review for gene: CCDC174 was set to AMBER
Added comment: Biallelic pathogenic CCDC174 variants cause Hypotonia, infantile, with psychomotor retardation - IHPMR (MIM 616816). Volodarsky et al [2015 - PMID: 26358778] describe 6 children from 2 unrelated families with - among others - severe hypotonia, psychomotor delay and abducens nerve palsy. All affected subjects were homozygous for a stoploss variant. Evidence from functional studies/animal model is provided supporting the role of the gene in this phenotype. Overall this gene can be considered for inclusion in the ID panel with amber rating (2 families, single founder variant, consistent phenotype, supportive studies) pending further reports.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.2755 CCDC174 Zornitza Stark Marked gene: CCDC174 as ready
Intellectual disability syndromic and non-syndromic v0.2755 CCDC174 Zornitza Stark Gene: ccdc174 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2755 CCDC174 Zornitza Stark Classified gene: CCDC174 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2755 CCDC174 Zornitza Stark Gene: ccdc174 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3320 ACOX2 Zornitza Stark Classified gene: ACOX2 as Green List (high evidence)
Mendeliome v0.3320 ACOX2 Zornitza Stark Gene: acox2 has been classified as Green List (High Evidence).
Mendeliome v0.3319 ACOX2 Zornitza Stark edited their review of gene: ACOX2: Added comment: Third family reported.; Changed rating: GREEN; Changed publications: 27647924, 27884763, 29287774
Peroxisomal Disorders v0.4 ACOX2 Zornitza Stark Publications for gene: ACOX2 were set to 27647924; 27884763
Peroxisomal Disorders v0.3 ACOX2 Zornitza Stark Classified gene: ACOX2 as Green List (high evidence)
Peroxisomal Disorders v0.3 ACOX2 Zornitza Stark Gene: acox2 has been classified as Green List (High Evidence).
Peroxisomal Disorders v0.2 ACOX2 Zornitza Stark edited their review of gene: ACOX2: Added comment: Third family reported.; Changed rating: GREEN; Changed publications: 29287774; Changed phenotypes: Bile acid synthesis defect, congenital, 6, 617308; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2754 ACOX2 Zornitza Stark Marked gene: ACOX2 as ready
Intellectual disability syndromic and non-syndromic v0.2754 ACOX2 Zornitza Stark Gene: acox2 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2754 ACOX2 Zornitza Stark Classified gene: ACOX2 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.2754 ACOX2 Zornitza Stark Gene: acox2 has been classified as Red List (Low Evidence).
Mendeliome v0.3319 ABCA2 Zornitza Stark Marked gene: ABCA2 as ready
Mendeliome v0.3319 ABCA2 Zornitza Stark Gene: abca2 has been classified as Green List (High Evidence).
Mendeliome v0.3319 ABCA2 Zornitza Stark Classified gene: ABCA2 as Green List (high evidence)
Mendeliome v0.3319 ABCA2 Zornitza Stark Gene: abca2 has been classified as Green List (High Evidence).
Mendeliome v0.3318 ABCA2 Zornitza Stark gene: ABCA2 was added
gene: ABCA2 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: ABCA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABCA2 were set to 30237576; 29302074; 31047799
Phenotypes for gene: ABCA2 were set to Intellectual developmental disorder with poor growth and with or without seizures or ataxia, 618808
Review for gene: ABCA2 was set to GREEN
Added comment: Biallelic pathogenic ABCA2 variants cause Intellectual developmental disorder with poor growth and with or without seizures or ataxia (MIM 618808). There are 3 relevant publications (01-07-2020) : - Maddirevula et al [2019 - PMID: 30237576] described briefly 2 unrelated subjects (16-2987, 16DG0071) both DD and seizures among other manifestations. - Hu et al [2019 - PMID: 29302074] reported 3 sibs (M8600615 - III:1-3) born to consanguineous parents (M8600615 - III:1-3) with DD/ID (formal confirmation of moderate ID, in those (2) evaluated). One also presented with seizures. - Aslam and Naz [2019 - PMID: 31047799] provided clinical details on 2 siblings born to consanguineous parents. ID was reported for the older sib but was absent in the younger one. Seizures were not part of the phenotype. All subjects harbored biallelic pLoF variants. N.B. : Steinberg et al [2015 - PMID: 25773295], within a cohort of patients with ALS, identified one with biallelic ABCA2 variants. As however Aslam and Naz comment, this person harbored a single pathogenic variant, with a second one rather unlikely to be pathogenic due to high allele frequency. Overall this gene can be considered for inclusion with green rating in both ID and epilepsy panels (each in >=3 unrelated individuals).
Sources: Expert Review
Genetic Epilepsy v0.747 ABCA2 Zornitza Stark Marked gene: ABCA2 as ready
Genetic Epilepsy v0.747 ABCA2 Zornitza Stark Gene: abca2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.747 ABCA2 Zornitza Stark Classified gene: ABCA2 as Green List (high evidence)
Genetic Epilepsy v0.747 ABCA2 Zornitza Stark Gene: abca2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2753 ABCA2 Zornitza Stark Marked gene: ABCA2 as ready
Intellectual disability syndromic and non-syndromic v0.2753 ABCA2 Zornitza Stark Gene: abca2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2753 ABCA2 Zornitza Stark Classified gene: ABCA2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2753 ABCA2 Zornitza Stark Gene: abca2 has been classified as Green List (High Evidence).
Autism v0.103 HERC2 Zornitza Stark Marked gene: HERC2 as ready
Autism v0.103 HERC2 Zornitza Stark Gene: herc2 has been classified as Green List (High Evidence).
Autism v0.103 HERC2 Zornitza Stark Phenotypes for gene: HERC2 were changed from to Mental retardation, autosomal recessive 38 (MIM 615516)
Autism v0.102 HERC2 Zornitza Stark Publications for gene: HERC2 were set to
Autism v0.101 HERC2 Zornitza Stark Mode of inheritance for gene: HERC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Autism v0.100 HERC2 Zornitza Stark reviewed gene: HERC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23065719, 23243086, 30902390, 32571899, 27848944, 26077850, 27759030; Phenotypes: Mental retardation, autosomal recessive 38 (MIM 615516); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Angelman Rett like syndromes v0.11 HERC2 Zornitza Stark Marked gene: HERC2 as ready
Angelman Rett like syndromes v0.11 HERC2 Zornitza Stark Gene: herc2 has been classified as Green List (High Evidence).
Angelman Rett like syndromes v0.11 HERC2 Zornitza Stark Phenotypes for gene: HERC2 were changed from to Mental retardation, autosomal recessive 38 (MIM 615516)
Angelman Rett like syndromes v0.10 HERC2 Zornitza Stark Publications for gene: HERC2 were set to
Angelman Rett like syndromes v0.9 HERC2 Zornitza Stark Mode of inheritance for gene: HERC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Angelman Rett like syndromes v0.8 HERC2 Zornitza Stark reviewed gene: HERC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23065719, 23243086, 30902390, 32571899, 27848944, 26077850, 27759030; Phenotypes: Mental retardation, autosomal recessive 38 (MIM 615516); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3317 HERC2 Zornitza Stark Marked gene: HERC2 as ready
Mendeliome v0.3317 HERC2 Zornitza Stark Gene: herc2 has been classified as Green List (High Evidence).
Mendeliome v0.3317 HERC2 Zornitza Stark Phenotypes for gene: HERC2 were changed from to Mental retardation, autosomal recessive 38 (MIM 615516)
Mendeliome v0.3316 HERC2 Zornitza Stark Publications for gene: HERC2 were set to
Mendeliome v0.3315 HERC2 Zornitza Stark Mode of inheritance for gene: HERC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3314 HERC2 Zornitza Stark reviewed gene: HERC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23065719, 23243086, 30902390, 32571899, 27848944, 26077850, 27759030; Phenotypes: Mental retardation, autosomal recessive 38 (MIM 615516); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.746 HERC2 Zornitza Stark Marked gene: HERC2 as ready
Genetic Epilepsy v0.746 HERC2 Zornitza Stark Gene: herc2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.746 HERC2 Zornitza Stark Classified gene: HERC2 as Green List (high evidence)
Genetic Epilepsy v0.746 HERC2 Zornitza Stark Gene: herc2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2752 HERC2 Zornitza Stark Publications for gene: HERC2 were set to 23243086; 23065719
Intellectual disability syndromic and non-syndromic v0.2751 HERC2 Zornitza Stark Classified gene: HERC2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2751 HERC2 Zornitza Stark Gene: herc2 has been classified as Green List (High Evidence).
Mendeliome v0.3314 ALOX12 Zornitza Stark Marked gene: ALOX12 as ready
Mendeliome v0.3314 ALOX12 Zornitza Stark Gene: alox12 has been classified as Red List (Low Evidence).
Mendeliome v0.3314 ALOX12 Zornitza Stark Classified gene: ALOX12 as Red List (low evidence)
Mendeliome v0.3314 ALOX12 Zornitza Stark Gene: alox12 has been classified as Red List (Low Evidence).
Mendeliome v0.3313 ALOX12 Zornitza Stark reviewed gene: ALOX12: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.3313 ETF1 Zornitza Stark Marked gene: ETF1 as ready
Mendeliome v0.3313 ETF1 Zornitza Stark Gene: etf1 has been classified as Red List (Low Evidence).
Mendeliome v0.3313 ETF1 Zornitza Stark Classified gene: ETF1 as Red List (low evidence)
Mendeliome v0.3313 ETF1 Zornitza Stark Gene: etf1 has been classified as Red List (Low Evidence).
Mendeliome v0.3312 ETF1 Zornitza Stark reviewed gene: ETF1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.2750 TTI1 Zornitza Stark commented on gene: TTI1: Two unrelated consanguineous families previously described with homozygous missense variants, both in large cohort papers with multiple candidate genes in inbred population. No functional evidence provided, segregation uninformative.
Mendeliome v0.3312 TTI1 Zornitza Stark Phenotypes for gene: TTI1 were changed from to Intellectual disability
Mendeliome v0.3311 TTI1 Zornitza Stark Publications for gene: TTI1 were set to
Mendeliome v0.3310 TTI1 Zornitza Stark Mode of inheritance for gene: TTI1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2750 CNPY3 Konstantinos Varvagiannis gene: CNPY3 was added
gene: CNPY3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CNPY3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CNPY3 were set to 29394991; 30237576
Phenotypes for gene: CNPY3 were set to Epileptic encephalopathy, early infantile, 60 (MIM 617929)
Penetrance for gene: CNPY3 were set to Complete
Review for gene: CNPY3 was set to GREEN
Added comment: Biallelic CNPY3 mutations cause Epileptic encephalopathy, early infantile, 60 (MIM 617929).

The phenotype including among others hypotonia, intractable seizures, DD and ID has been first reported by Mutoh et al (2018 - PMID: 29394991) in 3 subjects from 2 families. Evidence was provided for the role of the gene (incl. mouse model) and pathogenicity of the identified variants (resulting in LoF).

Another subject with similar features of hypotonia, DD, intractable epilepsy, feeding problems has been described briefly by Maddirevula et al (2019 - PMID: 30237576).
Sources: Literature
Genetic Epilepsy v0.745 CNPY3 Konstantinos Varvagiannis reviewed gene: CNPY3: Rating: GREEN; Mode of pathogenicity: None; Publications: 29394991, 30237576; Phenotypes: Epileptic encephalopathy, early infantile, 60 (MIM 617929); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2750 KIF21B Konstantinos Varvagiannis gene: KIF21B was added
gene: KIF21B was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: KIF21B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KIF21B were set to 32415109
Phenotypes for gene: KIF21B were set to Global developmental delay; Intellectual disability; Abnormality of brain morphology; Microcephaly
Penetrance for gene: KIF21B were set to unknown
Mode of pathogenicity for gene: KIF21B 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: KIF21B was set to GREEN
Added comment: Asselin et al (2020 - PMID: 32415109) report on 4 individuals with KIF21B pathogenic variants. DD/ID (borderline intellectual functioning to severe ID) was a feature in all. Variable other findings included brain malformations (CCA) and microcephaly. 3 missense variants and a 4-bp insertion were identified, in 3 cases as de novo events while in a single subject the variant was inherited from the father who was also affected. The authors provide evidence for a role of KIF21B in the regulation of processes involved in cortical development and deleterious effect of the missense variants impeding neuronal migration and kinesin autoinhibition. Phenotypes specific to variants (e.g. CCA or microcephaly) were recapitulated in animal models. Missense variants are thought to exert a gain-of-function effect. As commented on, the 4-bp duplication (/frameshift) variant might not be pathogenic. In blood sample from the respective individual, RT-qPCR analysis suggested that haploinsufficiency (NMD) applies. Although Kif21b haploinsufficiency in mice was shown to lead to impaired neuronal positioning, the gene might partially tolerate LoF variants as also suggested by 28 such variants in gnomAD. Homozygous Kif21b ko mice display severe morphological abnormalities, partial loss of commissural fibers, cognitive deficits and altered synaptic transmission (several refs to previous studies provided by the authors).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2750 PAX1 Konstantinos Varvagiannis gene: PAX1 was added
gene: PAX1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature,Radboud University Medical Center, Nijmegen
Mode of inheritance for gene: PAX1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PAX1 were set to 29681087; 23851939; 28657137
Phenotypes for gene: PAX1 were set to Otofaciocervical syndrome 2, 615560
Penetrance for gene: PAX1 were set to Complete
Review for gene: PAX1 was set to AMBER
Added comment: Biallelic PAX1 pathogenic variants cause Otofaciocervical syndrome 2 (OMIM 615560).

Brief review of the literature suggests 3 relevant publications to date (04-07-2020).

2 individuals with DD and ID have been reported (Patil et al, 2018 - PMID: 29681087 and Pohl et al, 2013 - PMID: 23851939). Other subjects reported were only evaluated as newborns(mostly)/infants [Paganini et al, 2017 - PMID: 28657137, Patil et al, 2018 - PMID: 29681087].

While the first report by Pohl et al identified a homozygous missense variant supported by functional studies [NM_006192.5:c.497G>T - p.(Gly166Val)] subsequent ones identified homozygosity for pLoF mutations [Patil et al: NM_006192.4:c.1173_1174insGCCCG / Paganini et al: NM_006192:c.1104C>A - p.(Cys368*)].

As discussed by Pohl et al:

PAX1 encodes a transcription factor with critical role in pattern formation during embryogenesis. Study of the mouse Gly157Val (equivalent to human Gly166Val) Pax1 variant suggested reduced binding affinity (reduced transactivation of a regulatory sequence of the Nkx3-2 promoter) and hypofunctional nature of this variant.

Mouse models seem to recapitulate features of the disorder (skeletal, immunodeficiency) while the role of Pax1 in hearing process was thought to be supported by early expression (P6) in mouse cochlea.

Overall this gene can be considered for inclusion in the ID panel with amber/green rating.
Sources: Literature, Radboud University Medical Center, Nijmegen
Intellectual disability syndromic and non-syndromic v0.2750 TMEM106B Konstantinos Varvagiannis gene: TMEM106B was added
gene: TMEM106B was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: TMEM106B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TMEM106B were set to 29186371; 29444210; 32595021
Phenotypes for gene: TMEM106B were set to Leukodystrophy, hypomyelinating, 16 (MIM #617964)
Penetrance for gene: TMEM106B were set to Complete
Mode of pathogenicity for gene: TMEM106B 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: TMEM106B was set to GREEN
Added comment: 6 unrelated individuals with Leukodystrophy, hypomyelinating, 16 (MIM #617964) due to a recurrent TMEM106B variant have been reported to date in the literature (Simons et al 2017 - PMID: 29186371, Yan et al 2018 - PMID: 29444210, Ikemoto et al 2020 - PMID: 32595021).

While a 3 y.o. female described by Yan et al had DD (eg sitting at 9m, walking at 25m) with normal cognitive functioning, and a 38 y.o. female had borderline intellectual functioning (IQ 76), 4 affected individuals had ID. Among them, a 19 y.o. male with severe ID was also found to harbor a second de novo possibly damaging USP7 variant. Seizures have been reported in 2 unrelated subjects. [Clinical features are also summarized in table 1 - Ikemoto et al].

All harbored NM_001134232.2(TMEM106B):c.754G>A (p.Asp252Asn) which in almost all cases occurred as a de novo event. In a single case this variant was inherited from a mosaic parent with mild DD in infancy but normal cognition (reported by Simons et al).

As discussed by Ito et al (2018 - PMID: 30643851) the encoded protein is a structural component of the lysosomal membrane, playing a role on lysosome acidification. Acidity of the lysosome mediates multiple aspects of lysosomal function. Ito et al, using patient-derived fibroblasts assessed mRNA and protein levels. These were unaltered compared with controls. While TMEM106B had been previously shown to affect lysosome number, morphology and acidification, Ito et al demonstrated increased number of lysosomes in patient cells as well as impaired acidification compared to controls. As commented lysosomes are required for generation of myelin.

Recurrence of this missense variant, the presence of pLoF TMEM106B variants in gnomAD as well as the phenotypically normal Tmem106b null mice suggest that this variant may have a gain-of-function or dominant negative effect.

Genes for other forms of hypomyelinating lipodystrophy (incl. PLP1) have green rating in the ID panel.

Overall TMEM106B can be considered for the ID panel with green rating and the epilepsy panel with amber rating.
Sources: Literature
Genetic Epilepsy v0.745 TMEM106B Konstantinos Varvagiannis gene: TMEM106B was added
gene: TMEM106B was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TMEM106B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TMEM106B were set to 29186371; 29444210; 32595021
Phenotypes for gene: TMEM106B were set to Leukodystrophy, hypomyelinating, 16 (MIM #617964)
Penetrance for gene: TMEM106B were set to Complete
Mode of pathogenicity for gene: TMEM106B 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: TMEM106B was set to AMBER
Added comment: 6 unrelated individuals with Leukodystrophy, hypomyelinating, 16 (MIM #617964) due to a recurrent TMEM106B variant have been reported to date in the literature (Simons et al 2017 - PMID: 29186371, Yan et al 2018 - PMID: 29444210, Ikemoto et al 2020 - PMID: 32595021).

While a 3 y.o. female described by Yan et al had DD (eg sitting at 9m, walking at 25m) with normal cognitive functioning, and a 38 y.o. female had borderline intellectual functioning (IQ 76), 4 affected individuals had ID. Among them, a 19 y.o. male with severe ID was also found to harbor a second de novo possibly damaging USP7 variant. Seizures have been reported in 2 unrelated subjects. [Clinical features are also summarized in table 1 - Ikemoto et al].

All harbored NM_001134232.2(TMEM106B):c.754G>A (p.Asp252Asn) which in almost all cases occurred as a de novo event. In a single case this variant was inherited from a mosaic parent with mild DD in infancy but normal cognition (reported by Simons et al).

As discussed by Ito et al (2018 - PMID: 30643851) the encoded protein is a structural component of the lysosomal membrane, playing a role on lysosome acidification. Acidity of the lysosome mediates multiple aspects of lysosomal function. Ito et al, using patient-derived fibroblasts assessed mRNA and protein levels. These were unaltered compared with controls. While TMEM106B had been previously shown to affect lysosome number, morphology and acidification, Ito et al demonstrated increased number of lysosomes in patient cells as well as impaired acidification compared to controls. As commented lysosomes are required for generation of myelin.

Recurrence of this missense variant, the presence of pLoF TMEM106B variants in gnomAD as well as the phenotypically normal Tmem106b null mice suggest that this variant may have a gain-of-function or dominant negative effect.

Genes for other forms of hypomyelinating lipodystrophy (incl. PLP1) have green rating in the ID panel.

Overall TMEM106B can be considered for the ID panel with green rating and the epilepsy panel with amber rating.
Sources: Literature
Genetic Epilepsy v0.745 TBC1D2B Konstantinos Varvagiannis gene: TBC1D2B was added
gene: TBC1D2B was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TBC1D2B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBC1D2B were set to 32623794
Phenotypes for gene: TBC1D2B were set to Global developmental delay; Intellectual disability; Seizures; Gingival overgrowth; Behavioral abnormality; Abnormality of the mandible; Abnormality of brain morphology; Abnormality of the eye; Hearing abnormality
Penetrance for gene: TBC1D2B were set to Complete
Review for gene: TBC1D2B was set to GREEN
Added comment: Harms et al (2020 - PMID: 32623794) report on 3 unrelated individuals with biallelic pLoF TBC1D2B variants.

Features included cognitive impairment (mild ID in one case, regression at the age of 12y in another, hypotonia and delayed milestones in a third aged 8m), seizures (3/3 - variable age of onset) and/or gingival overgrowth (2/3 - prior to initiation of AEDs). Other findings included behavioral abnormalities, mandibular anomalies, abnormal brain imaging and ophthalmologic or (rarely) audiometric evaluations.

All were born to non-consanguineous couples and additional investigations were performed in some.

Variants were identified by WES or trio WGS, with Sanger confirmation/compatible segregation analyses.

In line with the pLoF variants, mRNA studies in fibroblasts from 2 unrelated affected individuals demonstrated significantly reduced (~80-90%) TBC1C2D mRNA levels compared to controls, restored following cycloheximide treatment. Protein was absent in patient fibroblasts.

TBC-domain containing GTPase activating proteins are known as key regulators of RAB GTPase activity. TBC1D2B was shown to colocalize with RAB5-positive endocytic vesicles. CRISPR/Cas9-mediated ko of TBC1D2B in HeLa cells suggested a role in EGF receptor endocytosis and decreased cell viability of TBC1D2B-deficient HeLa cells upon serum deprivation.

Genes encoding other TBC domain-containg GTPase-activating proteins, e.g. TBC1D7 and TBC1D20, TBC1D24 are associated with recessive neurodevelopmental disorders (with ID and/or seizures) and the pathophysiological defect in TBC1D2B-related disorder (deficit in vesicle trafficking and/or cell survival) is proposed to be similar to that of TBC1D24.

Overall this gene can be considered for inclusion with amber/green rating in the ID panel and green in epilepsy panel.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2750 TBC1D2B Konstantinos Varvagiannis gene: TBC1D2B was added
gene: TBC1D2B was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: TBC1D2B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBC1D2B were set to 32623794
Phenotypes for gene: TBC1D2B were set to Global developmental delay; Intellectual disability; Seizures; Gingival overgrowth; Behavioral abnormality; Abnormality of the mandible; Abnormality of brain morphology; Abnormality of the eye; Hearing abnormality
Penetrance for gene: TBC1D2B were set to Complete
Review for gene: TBC1D2B was set to AMBER
Added comment: Harms et al (2020 - PMID: 32623794) report on 3 unrelated individuals with biallelic pLoF TBC1D2B variants.

Features included cognitive impairment (mild ID in one case, regression at the age of 12y in another, hypotonia and delayed milestones in a third aged 8m), seizures (3/3 - variable age of onset) and/or gingival overgrowth (2/3 - prior to initiation of AEDs). Other findings included behavioral abnormalities, mandibular anomalies, abnormal brain imaging and ophthalmologic or (rarely) audiometric evaluations.

All were born to non-consanguineous couples and additional investigations were performed in some.

Variants were identified by WES or trio WGS, with Sanger confirmation/compatible segregation analyses.

In line with the pLoF variants, mRNA studies in fibroblasts from 2 unrelated affected individuals demonstrated significantly reduced (~80-90%) TBC1C2D mRNA levels compared to controls, restored following cycloheximide treatment. Protein was absent in patient fibroblasts.

TBC-domain containing GTPase activating proteins are known as key regulators of RAB GTPase activity. TBC1D2B was shown to colocalize with RAB5-positive endocytic vesicles. CRISPR/Cas9-mediated ko of TBC1D2B in HeLa cells suggested a role in EGF receptor endocytosis and decreased cell viability of TBC1D2B-deficient HeLa cells upon serum deprivation.

Genes encoding other TBC domain-containg GTPase-activating proteins, e.g. TBC1D7 and TBC1D20, TBC1D24 are associated with recessive neurodevelopmental disorders (with ID and/or seizures) and the pathophysiological defect in TBC1D2B-related disorder (deficit in vesicle trafficking and/or cell survival) is proposed to be similar to that of TBC1D24.

Overall this gene can be considered for inclusion with amber/green rating in the ID panel and green in epilepsy panel.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2750 EXOC2 Konstantinos Varvagiannis gene: EXOC2 was added
gene: EXOC2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: EXOC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOC2 were set to 32639540
Phenotypes for gene: EXOC2 were set to Global developmental delay; Intellectual disability; Abnormality of the face; Abnormality of brain morphology
Penetrance for gene: EXOC2 were set to Complete
Review for gene: EXOC2 was set to AMBER
Added comment: Van Bergen et al (2020 - PMID: 32639540) report on 3 individuals from 2 families, harboring biallelic EXOC2 mutations.

Clinical presentation included DD, ID (severe in 2 subjects from fam1, borderline intellectual functioning in fam2), dysmorphic features and brain abnormalities. Cerebellar anomalies were common to all with a molar tooth sign observed in one (1/3). Other findings limited to subjects from one family included acquired microcephaly, congenital contractures, spastic quadriplegia (each observed 2/3).

Previous investigations were in all cases non-diagnostic. WES identified biallelic EXOC2 mutations in all affected individuals.

EXOC2 encodes an exocyst subunit. The latter is an octameric complex, component of the membrane transport machinery, required for tethering and fusion of vesicles at the plasma membrane. As discussed ,vesicle transport is important for the development of brain and the function of neurons and glia. Exocyst function is also important for delivery of Arl13b to the primary cilium (biallelic ARL13B mutations cause Joubert syndrome 8) and ciliogenesis.

Affected subjects from a broader consanguineous family (fam1) were homozygous for a truncating variant. Fibroblast studies revealed mRNA levels compatible with NMD (further restored in presence of CHX) as well as reduced protein levels. The female belonging to the second non-consanguineous family was found to harbor 2 missense variants in trans configuration.

An exocytosis defect was demonstrated in fibroblasts from individuals belonging to both families. Ciliogenesis appeared to be normal, however Arl13b localization/recruitment to the cilia was reduced compared with control cells with the defect rescued upon exogenous expression of wt EXOC2.

Mutations in other genes encoding components of the exocyst complex have been previously reported in individuals with relevant phenotypes (e.g. EXOC8 in a boy with features of Joubert s. or EXOC4 in nephrotic syndrome).

The authors discuss on the essential role of EXOC2 based on model organism studies (e.g. impaired neuronal membrane traffic, failure of neuronal polarization and neuromuscular junction expansion seen in Drosophila Sec5 (EXOC2) null mutants).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2750 CEP120 Konstantinos Varvagiannis gene: CEP120 was added
gene: CEP120 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CEP120 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP120 were set to 27208211
Phenotypes for gene: CEP120 were set to Joubert syndrome 31 (MIM 617761); Short-rib thoracic dysplasia 13 with or without polydactyly (MIM 616300)
Penetrance for gene: CEP120 were set to Complete
Review for gene: CEP120 was set to GREEN
Added comment: Pathogenic CEP120 variants have been reported in recessive ciliopathies, namely Short-rib thoracic dysplasia 13 with or without polydactyly (MIM 616300) and Joubert syndrome 31 (MIM 617761).

The former is associated with a severe/lethal outcome (4 unrelated infants described by Shaheen et al 2015 - PMID: 25361962, 2 fetuses reported by Roosing et al 2016 - PMID: 27208211).

Roosing et al however, also provided details on 4 unrelated subjects with Joubert syndrome diagnosis. All presented with a neurologic phenotype of hypotonia, DD, cognitive impairment and exhibited a molar tooth sign.

As a result, this gene can be considered for inclusion in the ID panel with green rating (>3 individuals/variants, consistent ciliopathy phenotype).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2750 CCDC174 Konstantinos Varvagiannis gene: CCDC174 was added
gene: CCDC174 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CCDC174 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC174 were set to 26358778
Phenotypes for gene: CCDC174 were set to Hypotonia, infantile, with psychomotor retardation - IHPMR, 616816
Penetrance for gene: CCDC174 were set to Complete
Mode of pathogenicity for gene: CCDC174 was set to Other
Review for gene: CCDC174 was set to AMBER
Added comment: Biallelic pathogenic CCDC174 variants cause Hypotonia, infantile, with psychomotor retardation - IHPMR (MIM 616816).

Volodarsky et al [2015 - PMID: 26358778] describe 6 children from 2 unrelated families with - among others - severe hypotonia, psychomotor delay and abducens nerve palsy. All affected subjects were homozygous for a stoploss variant. Evidence from functional studies/animal model is provided supporting the role of the gene in this phenotype.

Overall this gene can be considered for inclusion in the ID panel with amber rating (2 families, single founder variant, consistent phenotype, supportive studies) pending further reports.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2750 ACOX2 Konstantinos Varvagiannis gene: ACOX2 was added
gene: ACOX2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ACOX2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACOX2 were set to 27647924; 27884763; 29287774
Phenotypes for gene: ACOX2 were set to Bile acid synthesis defect, congenital, 6 - 617308
Penetrance for gene: ACOX2 were set to unknown
Review for gene: ACOX2 was set to RED
Added comment: Biallelic pathogenic ACOX2 variants cause Bile acid synthesis defect, congenital, 6 (MIM 617308). Overall the phenotype corresponds to an IEM/peroxisomal disorder.

As per 01-07-2020 there are 3 reports, briefly reviewed :

- Vilarinho et al [2016 - PMID: 27647924] provided details on an 8-year-old boy with ID.
- Monte et al [2017 - PMID: 27884763] described a 16 year old male with sustained elevation of transaminases *without* accompanying neurologic symptomatology (as they comment).
- Ferdinandusse et al [2018 - PMID: 29287774] reported on a girl deceased at the age of few months.

Please consider inclusion in the ID panel with amber/red rating pending further reports.
Sources: Literature
Genetic Epilepsy v0.745 ABCA2 Konstantinos Varvagiannis gene: ABCA2 was added
gene: ABCA2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: ABCA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABCA2 were set to 30237576; 29302074; 31047799
Phenotypes for gene: ABCA2 were set to Intellectual developmental disorder with poor growth and with or without seizures or ataxia, 618808
Penetrance for gene: ABCA2 were set to Complete
Review for gene: ABCA2 was set to GREEN
Added comment: Biallelic pathogenic ABCA2 variants cause Intellectual developmental disorder with poor growth and with or without seizures or ataxia (MIM 618808).

There are 3 relevant publications (01-07-2020) :
- Maddirevula et al [2019 - PMID: 30237576] described briefly 2 unrelated subjects (16-2987, 16DG0071) both DD and seizures among other manifestations.
- Hu et al [2019 - PMID: 29302074] reported 3 sibs (M8600615 - III:1-3) born to consanguineous parents (M8600615 - III:1-3) with DD/ID (formal confirmation of moderate ID, in those (2) evaluated). One also presented with seizures.
- Aslam and Naz [2019 - PMID: 31047799] provided clinical details on 2 siblings born to consanguineous parents. ID was reported for the older sib but was absent in the younger one. Seizures were not part of the phenotype.

All subjects harbored biallelic pLoF variants.

N.B. : Steinberg et al [2015 - PMID: 25773295], within a cohort of patients with ALS, identified one with biallelic ABCA2 variants. As however Aslam and Naz comment, this person harbored a single pathogenic variant, with a second one rather unlikely to be pathogenic due to high allele frequency.

Overall this gene can be considered for inclusion with green rating in both ID and epilepsy panels (each in >=3 unrelated individuals).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2750 ABCA2 Konstantinos Varvagiannis gene: ABCA2 was added
gene: ABCA2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ABCA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABCA2 were set to 30237576; 29302074; 31047799
Phenotypes for gene: ABCA2 were set to Intellectual developmental disorder with poor growth and with or without seizures or ataxia, 618808
Penetrance for gene: ABCA2 were set to Complete
Review for gene: ABCA2 was set to GREEN
Added comment: Biallelic pathogenic ABCA2 variants cause Intellectual developmental disorder with poor growth and with or without seizures or ataxia (MIM 618808).

There are 3 relevant publications (01-07-2020) :
- Maddirevula et al [2019 - PMID: 30237576] described briefly 2 unrelated subjects (16-2987, 16DG0071) both DD and seizures among other manifestations.
- Hu et al [2019 - PMID: 29302074] reported 3 sibs (M8600615 - III:1-3) born to consanguineous parents (M8600615 - III:1-3) with DD/ID (formal confirmation of moderate ID, in those (2) evaluated). One also presented with seizures.
- Aslam and Naz [2019 - PMID: 31047799] provided clinical details on 2 siblings born to consanguineous parents. ID was reported for the older sib but was absent in the younger one. Seizures were not part of the phenotype.

All subjects harbored biallelic pLoF variants.

N.B. : Steinberg et al [2015 - PMID: 25773295], within a cohort of patients with ALS, identified one with biallelic ABCA2 variants. As however Aslam and Naz comment, this person harbored a single pathogenic variant, with a second one rather unlikely to be pathogenic due to high allele frequency.

Overall this gene can be considered for inclusion with green rating in both ID and epilepsy panels (each in >=3 unrelated individuals).
Sources: Literature
Genetic Epilepsy v0.745 HERC2 Konstantinos Varvagiannis gene: HERC2 was added
gene: HERC2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: HERC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HERC2 were set to 23065719; 23243086; 30902390; 32571899; 27848944; 26077850; 27759030
Phenotypes for gene: HERC2 were set to Mental retardation, autosomal recessive 38 (MIM 615516)
Penetrance for gene: HERC2 were set to Complete
Review for gene: HERC2 was set to GREEN
Added comment: Biallelic pathogenic HERC2 variants cause Mental retardation, autosomal recessive 38 (MIM 615516).

The current review is based mostly on the information provided by Elpidorou et al (2020 - PMID: 32571899) summarizing the findings in several affected individuals as published in the literature. ID was a universal feature among them (27/27) and seizures were reported in some (9/27):
- 22 subjects from Amish/Mennonite families were homozygous for p.Pro594Leu [NM_004667.5(HERC2):c.1781C>T] (Puffenberger et al 2012 - PMID: 23065719, Harlalka et al 2013 - PMID: 23243086, Abraham et al - PMID: 30902390)
- 2 additional patients were homozygous for another missense SNV [NM_004667.5(HERC2):c.4625G>A - p.Arg1542His] (Abraham et al 2019 - PMID: 30902390)
- 3 sibs born to consanguineous parents, homozygous for NM_004667.5:c.13767_13770delTGAA - p.(Asn4589LysTer4598)] as described by Elpidorou et al.
- 1 male homozygous 286 kb deletion spanning several 5' exons of HERC2 as well as the first exons of OCA2 was described by Morice-Picard et al (2016 - PMID: 27759030). Despite a neurological presentation (axial hypotonia, peripheral hypertonia, extrapyramidal symptoms and uncoordinated movements) further information was not available.

Apart from the cases summarized by Elpidorou et al, there have been few additional ones e.g. :
- Trujillano et al (2017 - PMID: 27848944) reported briefly on a patient, homozygous for NM_004667.5:c.4676-1G>A displaying seizures, hypotonia, global DD, "Encephalopathy" and abnormality of the liver.
- Yavarna et al (2015 - PMID: 26077850) provided few details with on an individual with primarily 'neurocognitive' phenotype but rather atypical presentation (MRI abnormalities, TGA, VSD, renal anomaly, growth retardation, hearing loss) due to p.Q3164X variant (recessive inheritance was specified).

Several lines of evidence support an important role for the protein encoded (an E3 ubiquitin protein ligase, interacting also with UBE3A, involved in several cellular processes incl. cell cycle regulation, spindle formation during mitosis, mitochondrial functions, DNA damage responses by targeting proteins such as XPA) as well as the effect of the reported variants (mRNA studies, Western blot, detection of a fusion transcript in the case of the deletion, etc).

Individuals from the Amish families displayed Angelman-like features (in line with HERC2-UBE3A interaction) with - among others - gait instability. Mouse models recapitulate some of these features (e.g. the movement disorder) as extensively discussed by Abraham et al.

Overall this gene can be included in the ID and epilepsy panels with green rating.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2750 HERC2 Konstantinos Varvagiannis reviewed gene: HERC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23065719, 23243086, 30902390, 32571899, 27848944, 26077850, 27759030; Phenotypes: Mental retardation, autosomal recessive 38 (MIM 615516); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Aortopathy_Connective Tissue Disorders v0.160 PTDSS1 Zornitza Stark Marked gene: PTDSS1 as ready
Aortopathy_Connective Tissue Disorders v0.160 PTDSS1 Zornitza Stark Gene: ptdss1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.69 PCSK1 Zornitza Stark reviewed gene: PCSK1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Obesity with impaired prohormone processing (MIM#600955); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.69 PCSK1 Zornitza Stark Marked gene: PCSK1 as ready
Differences of Sex Development v0.69 PCSK1 Zornitza Stark Gene: pcsk1 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.69 PCSK1 Zornitza Stark Phenotypes for gene: PCSK1 were changed from to Obesity with impaired prohormone processing (MIM#600955)
Differences of Sex Development v0.68 PCSK1 Zornitza Stark Publications for gene: PCSK1 were set to
Differences of Sex Development v0.67 PCSK1 Zornitza Stark Classified gene: PCSK1 as Amber List (moderate evidence)
Differences of Sex Development v0.67 PCSK1 Zornitza Stark Gene: pcsk1 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.66 PROK2 Zornitza Stark Marked gene: PROK2 as ready
Differences of Sex Development v0.66 PROK2 Zornitza Stark Added comment: Comment when marking as ready: Evidence supporting association between bi-allelic variants causing IHH is stronger than for mono-allelic disease.
Differences of Sex Development v0.66 PROK2 Zornitza Stark Gene: prok2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.66 PROK2 Zornitza Stark Phenotypes for gene: PROK2 were changed from to Hypogonadotropic hypogonadism 4 with or without anosmia (MIM#610628)
Differences of Sex Development v0.65 PROK2 Zornitza Stark Publications for gene: PROK2 were set to
Differences of Sex Development v0.64 PROK2 Zornitza Stark Mode of inheritance for gene: PROK2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Differences of Sex Development v0.63 PROP1 Zornitza Stark Marked gene: PROP1 as ready
Differences of Sex Development v0.63 PROP1 Zornitza Stark Gene: prop1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.63 PROP1 Zornitza Stark Phenotypes for gene: PROP1 were changed from to Pituitary hormone deficiency, combined, 2 (MIM#262600)
Differences of Sex Development v0.62 PROP1 Zornitza Stark Publications for gene: PROP1 were set to
Differences of Sex Development v0.61 PROP1 Zornitza Stark Mode of inheritance for gene: PROP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2750 RPL10 Zornitza Stark Marked gene: RPL10 as ready
Intellectual disability syndromic and non-syndromic v0.2750 RPL10 Zornitza Stark Gene: rpl10 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2750 RPL10 Zornitza Stark Phenotypes for gene: RPL10 were changed from to Mental retardation, X-linked, syndromic, 35 (MIM#300998)
Intellectual disability syndromic and non-syndromic v0.2749 RPL10 Zornitza Stark Publications for gene: RPL10 were set to
Intellectual disability syndromic and non-syndromic v0.2748 RPL10 Zornitza Stark Mode of inheritance for gene: RPL10 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Differences of Sex Development v0.60 RPL10 Zornitza Stark Marked gene: RPL10 as ready
Differences of Sex Development v0.60 RPL10 Zornitza Stark Gene: rpl10 has been classified as Green List (High Evidence).
Differences of Sex Development v0.60 RPL10 Zornitza Stark Classified gene: RPL10 as Green List (high evidence)
Differences of Sex Development v0.60 RPL10 Zornitza Stark Gene: rpl10 has been classified as Green List (High Evidence).
Differences of Sex Development v0.59 SAMD9 Zornitza Stark Marked gene: SAMD9 as ready
Differences of Sex Development v0.59 SAMD9 Zornitza Stark Gene: samd9 has been classified as Green List (High Evidence).
Differences of Sex Development v0.59 SAMD9 Zornitza Stark Classified gene: SAMD9 as Green List (high evidence)
Differences of Sex Development v0.59 SAMD9 Zornitza Stark Gene: samd9 has been classified as Green List (High Evidence).
Differences of Sex Development v0.58 SEMA3E Zornitza Stark Marked gene: SEMA3E as ready
Differences of Sex Development v0.58 SEMA3E Zornitza Stark Gene: sema3e has been classified as Red List (Low Evidence).
Differences of Sex Development v0.58 SEMA3E Zornitza Stark Classified gene: SEMA3E as Red List (low evidence)
Differences of Sex Development v0.58 SEMA3E Zornitza Stark Gene: sema3e has been classified as Red List (Low Evidence).
Differences of Sex Development v0.57 SGPL1 Zornitza Stark Marked gene: SGPL1 as ready
Differences of Sex Development v0.57 SGPL1 Zornitza Stark Gene: sgpl1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.57 SGPL1 Zornitza Stark Classified gene: SGPL1 as Green List (high evidence)
Differences of Sex Development v0.57 SGPL1 Zornitza Stark Gene: sgpl1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.365 SOX10 Zornitza Stark Marked gene: SOX10 as ready
Deafness_IsolatedAndComplex v0.365 SOX10 Zornitza Stark Gene: sox10 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.365 SOX10 Zornitza Stark Phenotypes for gene: SOX10 were changed from to PCWH syndrome (MIM#609136); Waardenburg syndrome, type 2E, with or without neurologic involvement (MIM#611584); Waardenburg syndrome, type 4C (MIM#613266)
Deafness_IsolatedAndComplex v0.364 SOX10 Zornitza Stark Publications for gene: SOX10 were set to
Deafness_IsolatedAndComplex v0.363 SOX10 Zornitza Stark Mode of inheritance for gene: SOX10 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.56 SOX10 Zornitza Stark Marked gene: SOX10 as ready
Differences of Sex Development v0.56 SOX10 Zornitza Stark Gene: sox10 has been classified as Green List (High Evidence).
Differences of Sex Development v0.56 SOX10 Zornitza Stark Phenotypes for gene: SOX10 were changed from PCWH syndrome (MIM#609136); Waardenburg syndrome, type 2E, with or without neurologic involvement (MIM#611584); Waardenburg syndrome, type 4C (MIM#613266) to Kallman syndrome; PCWH syndrome (MIM#609136); Waardenburg syndrome, type 2E, with or without neurologic involvement (MIM#611584); Waardenburg syndrome, type 4C (MIM#613266)
Differences of Sex Development v0.55 SOX10 Zornitza Stark Classified gene: SOX10 as Green List (high evidence)
Differences of Sex Development v0.55 SOX10 Zornitza Stark Gene: sox10 has been classified as Green List (High Evidence).
Differences of Sex Development v0.54 TAC3 Zornitza Stark Marked gene: TAC3 as ready
Differences of Sex Development v0.54 TAC3 Zornitza Stark Gene: tac3 has been classified as Green List (High Evidence).
Differences of Sex Development v0.54 TAC3 Zornitza Stark Phenotypes for gene: TAC3 were changed from to Hypogonadotropic hypogonadism 10 with or without anosmia (MIM#614839)
Differences of Sex Development v0.53 TAC3 Zornitza Stark Publications for gene: TAC3 were set to
Differences of Sex Development v0.52 TAC3 Zornitza Stark Mode of inheritance for gene: TAC3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.51 TOE1 Zornitza Stark Marked gene: TOE1 as ready
Differences of Sex Development v0.51 TOE1 Zornitza Stark Gene: toe1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.51 TOE1 Zornitza Stark Classified gene: TOE1 as Green List (high evidence)
Differences of Sex Development v0.51 TOE1 Zornitza Stark Gene: toe1 has been classified as Green List (High Evidence).
Mendeliome v0.3309 SGMS2 Bryony Thompson Marked gene: SGMS2 as ready
Mendeliome v0.3309 SGMS2 Bryony Thompson Gene: sgms2 has been classified as Green List (High Evidence).
Mendeliome v0.3309 SGMS2 Bryony Thompson Classified gene: SGMS2 as Green List (high evidence)
Mendeliome v0.3309 SGMS2 Bryony Thompson Gene: sgms2 has been classified as Green List (High Evidence).
Mendeliome v0.3308 SGMS2 Bryony Thompson gene: SGMS2 was added
gene: SGMS2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SGMS2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SGMS2 were set to 30779713; 32028018
Phenotypes for gene: SGMS2 were set to Calvarial doughnut lesions with bone fragility with or without spondylometaphyseal dysplasia MIM#126550
Review for gene: SGMS2 was set to GREEN
Added comment: 12 patients from 6 unrelated families with the same stopgain variant (p.Arg50*), with osteoporosis that resembles osteogenesis imperfecta. In vitro over-expression assays of the variant demonstrate protein that was completely mislocalized in the cytosolic and nuclear compartments. 2 unrelated families were heterozygous for 2 missense (p.Ile62Ser, p.Met64Arg) with bone fragility and severe short stature, and spondylometaphyseal dysplasia. In vitro assays of each variant demonstrated an enhanced rate of de novo sphingomyelin production by blocking export of a functional enzyme from the endoplasmic reticulum.
Sources: Expert list
Osteopetrosis v0.3 SGMS2 Bryony Thompson Marked gene: SGMS2 as ready
Osteopetrosis v0.3 SGMS2 Bryony Thompson Gene: sgms2 has been classified as Green List (High Evidence).
Osteopetrosis v0.3 SGMS2 Bryony Thompson Classified gene: SGMS2 as Green List (high evidence)
Osteopetrosis v0.3 SGMS2 Bryony Thompson Gene: sgms2 has been classified as Green List (High Evidence).
Osteopetrosis v0.2 SGMS2 Bryony Thompson gene: SGMS2 was added
gene: SGMS2 was added to Osteopetrosis. Sources: Literature
Mode of inheritance for gene: SGMS2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SGMS2 were set to 30779713; 32028018
Phenotypes for gene: SGMS2 were set to Calvarial doughnut lesions with bone fragility with or without spondylometaphyseal dysplasia MIM#126550
Review for gene: SGMS2 was set to GREEN
Added comment: 12 patients from 6 unrelated families with the same stopgain variant (p.Arg50*), with osteoporosis that resembles osteogenesis imperfecta. In vitro over-expression assays of the variant demonstrate protein that was completely mislocalized in the cytosolic and nuclear compartments. 2 unrelated families were heterozygous for 2 missense (p.Ile62Ser, p.Met64Arg) with bone fragility and severe short stature, and spondylometaphyseal dysplasia. In vitro assays of each variant demonstrated an enhanced rate of de novo sphingomyelin production by blocking export of a functional enzyme from the endoplasmic reticulum.
Sources: Literature
Osteogenesis Imperfecta and Osteoporosis v0.26 SGMS2 Bryony Thompson Marked gene: SGMS2 as ready
Osteogenesis Imperfecta and Osteoporosis v0.26 SGMS2 Bryony Thompson Gene: sgms2 has been classified as Green List (High Evidence).
Osteogenesis Imperfecta and Osteoporosis v0.26 SGMS2 Bryony Thompson Classified gene: SGMS2 as Green List (high evidence)
Osteogenesis Imperfecta and Osteoporosis v0.26 SGMS2 Bryony Thompson Gene: sgms2 has been classified as Green List (High Evidence).
Osteogenesis Imperfecta and Osteoporosis v0.25 SGMS2 Bryony Thompson gene: SGMS2 was added
gene: SGMS2 was added to Osteogenesis Imperfecta. Sources: Expert list
Mode of inheritance for gene: SGMS2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SGMS2 were set to 30779713; 32028018
Phenotypes for gene: SGMS2 were set to Calvarial doughnut lesions with bone fragility with or without spondylometaphyseal dysplasia MIM#126550
Review for gene: SGMS2 was set to GREEN
Added comment: 12 patients from 6 unrelated families with the same stopgain variant (p.Arg50*), with osteoporosis that resembles osteogenesis imperfecta. In vitro over-expression assays of the variant demonstrate protein that was completely mislocalized in the cytosolic and nuclear compartments.
2 unrelated families were heterozygous for 2 missense (p.Ile62Ser, p.Met64Arg) with bone fragility and severe short stature, and spondylometaphyseal dysplasia. In vitro assays of each variant demonstrated an enhanced rate of de novo sphingomyelin production by blocking export of a functional enzyme from the endoplasmic reticulum.
Sources: Expert list
Osteogenesis Imperfecta and Osteoporosis v0.24 UNC45A Bryony Thompson Marked gene: UNC45A as ready
Osteogenesis Imperfecta and Osteoporosis v0.24 UNC45A Bryony Thompson Gene: unc45a has been classified as Amber List (Moderate Evidence).
Osteogenesis Imperfecta and Osteoporosis v0.24 UNC45A Bryony Thompson Phenotypes for gene: UNC45A were changed from to cholestasis; congenital diarrhea; impaired hearing; bone fragility
Osteogenesis Imperfecta and Osteoporosis v0.23 UNC45A Bryony Thompson Publications for gene: UNC45A were set to
Osteogenesis Imperfecta and Osteoporosis v0.22 UNC45A Bryony Thompson Mode of inheritance for gene: UNC45A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Pituitary hormone deficiency v0.1 Seb Lunke Panel types changed to Victorian Clinical Genetics Services; Rare Disease
Pituitary hormone deficiency v0.0 ZSWIM6 Seb Lunke gene: ZSWIM6 was added
gene: ZSWIM6 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: ZSWIM6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: ZSWIM6 were set to Neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic features (617865); Acromelic frontonasal dysostosis (603671)
Pituitary hormone deficiency v0.0 ZIC2 Seb Lunke gene: ZIC2 was added
gene: ZIC2 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: ZIC2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ZIC2 were set to 24706429
Phenotypes for gene: ZIC2 were set to Holoprosencephaly 5 (609637)
Pituitary hormone deficiency v0.0 WDR11 Seb Lunke gene: WDR11 was added
gene: WDR11 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: WDR11 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: WDR11 were set to Hypogonadotropic hypogonadism 14 with or without anosmia (614858)
Pituitary hormone deficiency v0.0 TGIF1 Seb Lunke gene: TGIF1 was added
gene: TGIF1 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: TGIF1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TGIF1 were set to 23476075
Phenotypes for gene: TGIF1 were set to Holoprosencephaly 4 (142946)
Pituitary hormone deficiency v0.0 SLC20A1 Seb Lunke gene: SLC20A1 was added
gene: SLC20A1 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: SLC20A1 was set to Unknown
Phenotypes for gene: SLC20A1 were set to No OMIM number
Pituitary hormone deficiency v0.0 SLC15A4 Seb Lunke gene: SLC15A4 was added
gene: SLC15A4 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: SLC15A4 was set to Unknown
Publications for gene: SLC15A4 were set to 29261175
Phenotypes for gene: SLC15A4 were set to No OMIM number
Pituitary hormone deficiency v0.0 SIX3 Seb Lunke gene: SIX3 was added
gene: SIX3 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: SIX3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: SIX3 were set to Holoprosencephaly 2 (157170)
Pituitary hormone deficiency v0.0 RBM28 Seb Lunke gene: RBM28 was added
gene: RBM28 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: RBM28 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RBM28 were set to 20231366
Phenotypes for gene: RBM28 were set to ANE syndrome; ?Alopecia, neurologic defects, and endocrinopathy syndrome (612079)
Pituitary hormone deficiency v0.0 PTCH1 Seb Lunke gene: PTCH1 was added
gene: PTCH1 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: PTCH1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PTCH1 were set to 11941477
Phenotypes for gene: PTCH1 were set to Holoprosencephaly 7 (610828)
Pituitary hormone deficiency v0.0 PSTPIP1 Seb Lunke gene: PSTPIP1 was added
gene: PSTPIP1 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: PSTPIP1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: PSTPIP1 were set to Holoprosencephaly; Pyogenic sterile arthritis, pyoderma gangrenosum, and acne (604416)
Pituitary hormone deficiency v0.0 POLR3A Seb Lunke gene: POLR3A was added
gene: POLR3A was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: POLR3A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: POLR3A were set to Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism (607694)
Pituitary hormone deficiency v0.0 PAX6 Seb Lunke gene: PAX6 was added
gene: PAX6 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: PAX6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PAX6 were set to 25342853
Phenotypes for gene: PAX6 were set to Aniridia (106210)
Pituitary hormone deficiency v0.0 NODAL Seb Lunke gene: NODAL was added
gene: NODAL was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: NODAL was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: NODAL were set to Holoprosencephaly; Heterotaxy, visceral, 5 (270100)
Pituitary hormone deficiency v0.0 HNRNPU Seb Lunke gene: HNRNPU was added
gene: HNRNPU was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: HNRNPU was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: HNRNPU were set to Epileptic encephalopathy, early infantile, 54 (617391)
Pituitary hormone deficiency v0.0 HHIP Seb Lunke gene: HHIP was added
gene: HHIP was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: HHIP was set to Unknown
Phenotypes for gene: HHIP were set to No OMIM number
Pituitary hormone deficiency v0.0 GPR161 Seb Lunke gene: GPR161 was added
gene: GPR161 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: GPR161 was set to Unknown
Publications for gene: GPR161 were set to 25322266
Phenotypes for gene: GPR161 were set to No OMIM number; pituitary stalk interruption syndrome
Pituitary hormone deficiency v0.0 GHRH Seb Lunke gene: GHRH was added
gene: GHRH was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: GHRH was set to Unknown
Publications for gene: GHRH were set to 15155578
Phenotypes for gene: GHRH were set to No OMIM number; ?Isolated growth hormone deficiency due to defect in GHRF
Pituitary hormone deficiency v0.0 FOXH1 Seb Lunke gene: FOXH1 was added
gene: FOXH1 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: FOXH1 was set to Unknown
Phenotypes for gene: FOXH1 were set to Holoprosencephaly; No OMIM number
Pituitary hormone deficiency v0.0 BMP4 Seb Lunke gene: BMP4 was added
gene: BMP4 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: BMP4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: BMP4 were set to 24289245
Phenotypes for gene: BMP4 were set to Microphthalmia, syndromic 6 (607932)
Pituitary hormone deficiency v0.0 BMP2 Seb Lunke gene: BMP2 was added
gene: BMP2 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: BMP2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: BMP2 were set to 24289245
Phenotypes for gene: BMP2 were set to Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies (617877)
Pituitary hormone deficiency v0.0 ARNT2 Seb Lunke gene: ARNT2 was added
gene: ARNT2 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: ARNT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARNT2 were set to 24022475
Phenotypes for gene: ARNT2 were set to ?Webb-Dattani syndrome (615926)
Pituitary hormone deficiency v0.0 TCF7L1 Seb Lunke gene: TCF7L1 was added
gene: TCF7L1 was added to Pituitary hormone deficiency. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: TCF7L1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TCF7L1 were set to 26764381
Phenotypes for gene: TCF7L1 were set to No OMIM number; pituitary hormone deficiency
Pituitary hormone deficiency v0.0 SHH Seb Lunke gene: SHH was added
gene: SHH was added to Pituitary hormone deficiency. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: SHH was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SHH were set to 22897141
Phenotypes for gene: SHH were set to Microphthalmia with coloboma 5 (611638); Holoprosencephaly 3 (142945)
Pituitary hormone deficiency v0.0 KCNQ1 Seb Lunke gene: KCNQ1 was added
gene: KCNQ1 was added to Pituitary hormone deficiency. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: KCNQ1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KCNQ1 were set to 29097701
Phenotypes for gene: KCNQ1 were set to Pituitary hormone deficiency; Long QT syndrome 1 (192500)
Pituitary hormone deficiency v0.0 CDON Seb Lunke gene: CDON was added
gene: CDON was added to Pituitary hormone deficiency. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: CDON was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CDON were set to 21802063; 26529631
Phenotypes for gene: CDON were set to Holoprosencephaly 11 (614226)
Pituitary hormone deficiency v0.0 TBX19 Seb Lunke gene: TBX19 was added
gene: TBX19 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: TBX19 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBX19 were set to 22170728; 11290323; 15476446
Phenotypes for gene: TBX19 were set to Adrenocorticotropic hormone deficiency (201400)
Pituitary hormone deficiency v0.0 SOX3 Seb Lunke gene: SOX3 was added
gene: SOX3 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: SOX3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SOX3 were set to 24346842; 15800844; 21289259; 24737742
Phenotypes for gene: SOX3 were set to Panhypopituitarism, X-linked (312000); Mental retardation, X-linked, with isolated growth hormone deficiency (300123)
Pituitary hormone deficiency v0.0 SOX2 Seb Lunke gene: SOX2 was added
gene: SOX2 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: SOX2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SOX2 were set to 29371155; 16932809; 30450772
Phenotypes for gene: SOX2 were set to Microphthalmia, syndromic 3 (206900)
Pituitary hormone deficiency v0.0 PROP1 Seb Lunke gene: PROP1 was added
gene: PROP1 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: PROP1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PROP1 were set to Pituitary hormone deficiency, combined, 2 (262600)
Pituitary hormone deficiency v0.0 PROKR2 Seb Lunke gene: PROKR2 was added
gene: PROKR2 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: PROKR2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PROKR2 were set to 22319038; 25678757; 25759380
Phenotypes for gene: PROKR2 were set to Hypogonadotropic hypogonadism 3 with or without anosmia (244200)
Pituitary hormone deficiency v0.0 POU1F1 Seb Lunke gene: POU1F1 was added
gene: POU1F1 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: POU1F1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: POU1F1 were set to Pituitary hormone deficiency, combined, 1 (613038)
Pituitary hormone deficiency v0.0 PNPLA6 Seb Lunke gene: PNPLA6 was added
gene: PNPLA6 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: PNPLA6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PNPLA6 were set to 25033069
Phenotypes for gene: PNPLA6 were set to Oliver-McFarlane syndrome (275400); Spastic paraplegia 39, autosomal recessive (612020); Boucher-Neuhauser syndrome (215470)
Pituitary hormone deficiency v0.0 PITX2 Seb Lunke gene: PITX2 was added
gene: PITX2 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: PITX2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: PITX2 were set to Anterior segment dysgenesis 4 (137600); Axenfeld-Rieger syndrome, type 1 (180500)
Pituitary hormone deficiency v0.0 OTX2 Seb Lunke gene: OTX2 was added
gene: OTX2 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: OTX2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: OTX2 were set to 19965921; 22715480; 18628516; 18728160
Phenotypes for gene: OTX2 were set to Pituitary hormone deficiency, combined, 6 (613986); Microphthalmia, syndromic 5 (610125)
Pituitary hormone deficiency v0.0 LHX4 Seb Lunke gene: LHX4 was added
gene: LHX4 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: LHX4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: LHX4 were set to 18073311; 18445675; 11567216
Phenotypes for gene: LHX4 were set to Pituitary hormone deficiency, combined, 4 (262700)
Pituitary hormone deficiency v0.0 LHX3 Seb Lunke gene: LHX3 was added
gene: LHX3 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: LHX3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: LHX3 were set to Pituitary hormone deficiency, combined, 3 (221750)
Pituitary hormone deficiency v0.0 IGSF1 Seb Lunke gene: IGSF1 was added
gene: IGSF1 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: IGSF1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: IGSF1 were set to 23143598; 23966245; 26302767
Phenotypes for gene: IGSF1 were set to Hypothyroidism, central, and testicular enlargement (300888)
Pituitary hormone deficiency v0.0 HESX1 Seb Lunke gene: HESX1 was added
gene: HESX1 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: HESX1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: HESX1 were set to 14561704; 26781211; 11136712; 16940453
Phenotypes for gene: HESX1 were set to Growth hormone deficiency with pituitary anomalies (182230); Pituitary hormone deficiency, combined, 5 (182230)
Pituitary hormone deficiency v0.0 GNRHR Seb Lunke gene: GNRHR was added
gene: GNRHR was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: GNRHR was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GNRHR were set to Hypogonadotropic hypogonadism 7 without anosmia (146110)
Pituitary hormone deficiency v0.0 GLI3 Seb Lunke gene: GLI3 was added
gene: GLI3 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: GLI3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: GLI3 were set to 24736735; 15739154
Phenotypes for gene: GLI3 were set to Greig cephalopolysyndactyly syndrome (175700); Pallister-Hall syndrome (146510)
Pituitary hormone deficiency v0.0 GLI2 Seb Lunke gene: GLI2 was added
gene: GLI2 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: GLI2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: GLI2 were set to 14581620; 25878059
Phenotypes for gene: GLI2 were set to Culler-Jones syndrome (615849); Holoprosencephaly 9 (610829)
Pituitary hormone deficiency v0.0 GHSR Seb Lunke gene: GHSR was added
gene: GHSR was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: GHSR was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: GHSR were set to 19789204; 25557026
Phenotypes for gene: GHSR were set to Growth hormone deficiency, isolated partial (615925)
Pituitary hormone deficiency v0.0 GHRHR Seb Lunke gene: GHRHR was added
gene: GHRHR was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: GHRHR was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GHRHR were set to Growth hormone deficiency, isolated, type IV (618157)
Pituitary hormone deficiency v0.0 GHR Seb Lunke gene: GHR was added
gene: GHR was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: GHR was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GHR were set to Growth hormone insensitivity, partial (604271); Increased responsiveness to growth hormone (604271); Laron dwarfism (262500)
Pituitary hormone deficiency v0.0 GH1 Seb Lunke gene: GH1 was added
gene: GH1 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: GH1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: GH1 were set to Growth hormone deficiency, isolated, type IA (262400); Growth hormone deficiency, isolated, type IB (612781); Growth hormone deficiency, isolated, type II (173100)
Pituitary hormone deficiency v0.0 FOXA2 Seb Lunke gene: FOXA2 was added
gene: FOXA2 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: FOXA2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FOXA2 were set to 28973288; 29329447; 30414530
Phenotypes for gene: FOXA2 were set to No OMIM number; Congenital hyperinsulinism; Congenital hypopituitarism
Pituitary hormone deficiency v0.0 FGFR1 Seb Lunke gene: FGFR1 was added
gene: FGFR1 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: FGFR1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FGFR1 were set to 22319038; 25759380
Phenotypes for gene: FGFR1 were set to Jackson-Weiss syndrome (123150); Pfeiffer syndrome (101600); Hypogonadotropic hypogonadism 2 with or without anosmia (147950); Hartsfield syndrome (615465)
Pituitary hormone deficiency v0.0 FGF8 Seb Lunke gene: FGF8 was added
gene: FGF8 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: FGF8 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FGF8 were set to 22319038; 21832120; 20463092
Phenotypes for gene: FGF8 were set to Hypogonadotropic hypogonadism 6 with or without anosmia (612702)
Pituitary hormone deficiency v0.0 CHD7 Seb Lunke gene: CHD7 was added
gene: CHD7 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: CHD7 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: CHD7 were set to Hypogonadotropic hypogonadism 5 with or without anosmia (612370); CHARGE syndrome (214800)
Pituitary hormone deficiency v0.0 BTK Seb Lunke gene: BTK was added
gene: BTK was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: BTK was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: BTK were set to 9554752; 8013627; 7849697
Phenotypes for gene: BTK were set to Isolated growth hormone deficiency, type III, with agammaglobulinemia (307200)
Pituitary hormone deficiency v0.0 Seb Lunke Added panel Pituitary hormone deficiency
Aortopathy_Connective Tissue Disorders v0.160 PTDSS1 Bryony Thompson Classified gene: PTDSS1 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.160 PTDSS1 Bryony Thompson Gene: ptdss1 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.159 PTDSS1 Bryony Thompson gene: PTDSS1 was added
gene: PTDSS1 was added to Aortopathy_Connective Tissue Disorders. Sources: Expert list
Mode of inheritance for gene: PTDSS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTDSS1 were set to 24241535; 29341480; 31403251
Phenotypes for gene: PTDSS1 were set to Lenz-Majewski hyperostotic dwarfism MIM#151050
Mode of pathogenicity for gene: PTDSS1 was set to Other
Review for gene: PTDSS1 was set to GREEN
Added comment: 9 unrelated patients with cutis laxa as a prominent feature of a syndromic phenotype, with 5 different de novo (or assumed de novo) heterozygous missense mutations. Gain-of-function is the established or expected mechanism of disease for these variants.
Sources: Expert list
Differences of Sex Development v0.50 PCSK1 Crystle Lee reviewed gene: PCSK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23562752, 23800642, 17595246, 25272002, 27187081; Phenotypes: Obesity with impaired prohormone processing (MIM#600955); Mode of inheritance: None
Aortopathy_Connective Tissue Disorders v0.158 ATP6V1E1 Bryony Thompson Classified gene: ATP6V1E1 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.158 ATP6V1E1 Bryony Thompson Gene: atp6v1e1 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.157 ATP6V1E1 Bryony Thompson gene: ATP6V1E1 was added
gene: ATP6V1E1 was added to Aortopathy_Connective Tissue Disorders. Sources: Expert list
Mode of inheritance for gene: ATP6V1E1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP6V1E1 were set to 28065471; 27023906
Phenotypes for gene: ATP6V1E1 were set to Cutis laxa, autosomal recessive, type IIC MIM#617402
Review for gene: ATP6V1E1 was set to GREEN
Added comment: 3 unrelated consanguineous families from Iran, Kuwait, and Saudi Arabia, homozygous for 2 different missense variants (L128P, R212W) with paediatric onset cutis laxa, each segregating in an affected sibling. Molecular analyses of patient tissues was supportive: complexome profiling in cultured fibroblasts showed a markedly reduced abundance of the assembled V1 domain and of the complete membrane-bound V1V0 complex.
Sources: Expert list
Cutis Laxa v0.5 ATP6V1E1 Bryony Thompson changed review comment from: 3 unrelated consanguineous families homozygous for 2 different missense variants (L128P, R212W) with paediatric onset cutis laxa. Molecular anlayses of patient tissues was supportive.
Sources: Expert list; to: 3 unrelated consanguineous families homozygous for 2 different missense variants (L128P, R212W) with paediatric onset cutis laxa. Molecular analyses of patient tissues was supportive.
Sources: Expert list
Aortopathy_Connective Tissue Disorders v0.156 MAT2A Bryony Thompson Marked gene: MAT2A as ready
Aortopathy_Connective Tissue Disorders v0.156 MAT2A Bryony Thompson Gene: mat2a has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.156 MAT2A Bryony Thompson Classified gene: MAT2A as Amber List (moderate evidence)
Aortopathy_Connective Tissue Disorders v0.156 MAT2A Bryony Thompson Gene: mat2a has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.155 MAT2A Bryony Thompson gene: MAT2A was added
gene: MAT2A was added to Aortopathy_Connective Tissue Disorders. Sources: ClinGen
Mode of inheritance for gene: MAT2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAT2A were set to 30071989; 25557781
Phenotypes for gene: MAT2A were set to Thoracic aortic aneurysm
Review for gene: MAT2A was set to AMBER
Added comment: PMID: 25557781 - A rare missense (p.Glu344Ala) identified in a family that segregated with thoracic aortic disease and a second missense was identified in an unrelated thoracic aortic disease proband. Morpholino KO in zebrafish lead to pericardial edema and rescue by human MAT2A
PMID: 30071989 - Classified as Limited by the HTAAD GCEP, downgraded from Moderate due to the absence of additional variants identified in a large (>400) unpublished aortopathy cohort. Categorised as uncertain, because it is a recently reported gene-disease association.
Sources: ClinGen
Aortopathy_Connective Tissue Disorders v0.154 HCN4 Bryony Thompson Marked gene: HCN4 as ready
Aortopathy_Connective Tissue Disorders v0.154 HCN4 Bryony Thompson Gene: hcn4 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.154 HCN4 Bryony Thompson Classified gene: HCN4 as Amber List (moderate evidence)
Aortopathy_Connective Tissue Disorders v0.154 HCN4 Bryony Thompson Gene: hcn4 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.153 HCN4 Bryony Thompson gene: HCN4 was added
gene: HCN4 was added to Aortopathy_Connective Tissue Disorders. Sources: ClinGen
Mode of inheritance for gene: HCN4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HCN4 were set to 30071989; 27173043
Phenotypes for gene: HCN4 were set to Sick sinus syndrome 2 with cardiac noncompaction and ascending aorta dilation
Review for gene: HCN4 was set to AMBER
Added comment: PMID: 27173043 - Dilation of the ascending aorta was detected in 20 of 26 (77%) HCN4 mutation-positive cases from 7 unrelated families in whom images could be obtained to assess the ascending aorta.
PMID: 30071989 - Classified as Limited by the HTAAD GCEP, downgraded from Moderate due to the absence of aortic dissection and lack of longitudinal data on aortic growth. Categorised as uncertain, because it is a recently reported gene-disease association.
Sources: ClinGen
Differences of Sex Development v0.50 PROK2 Crystle Lee reviewed gene: PROK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 18559922, 17054399, 17959774, 18285834; Phenotypes: Hypogonadotropic hypogonadism 4 with or without anosmia (MIM#610628); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Differences of Sex Development v0.50 PROP1 Crystle Lee reviewed gene: PROP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15941866, 11549703; Phenotypes: Pituitary hormone deficiency, combined, 2 (MIM#262600); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3307 AKR1C4 Zornitza Stark Marked gene: AKR1C4 as ready
Mendeliome v0.3307 AKR1C4 Zornitza Stark Gene: akr1c4 has been classified as Red List (Low Evidence).
Mendeliome v0.3307 AKR1C4 Zornitza Stark Phenotypes for gene: AKR1C4 were changed from to {46XY sex reversal 8, modifier of}, MIM# 614279
Mendeliome v0.3306 AKR1C4 Zornitza Stark Publications for gene: AKR1C4 were set to
Mendeliome v0.3305 AKR1C4 Zornitza Stark Mode of inheritance for gene: AKR1C4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3304 AKR1C4 Zornitza Stark Classified gene: AKR1C4 as Red List (low evidence)
Mendeliome v0.3304 AKR1C4 Zornitza Stark Gene: akr1c4 has been classified as Red List (Low Evidence).
Mendeliome v0.3303 AKR1C4 Zornitza Stark reviewed gene: AKR1C4: Rating: RED; Mode of pathogenicity: None; Publications: 21802064; Phenotypes: {46XY sex reversal 8, modifier of}, MIM# 614279; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.50 AKR1C4 Zornitza Stark Marked gene: AKR1C4 as ready
Differences of Sex Development v0.50 AKR1C4 Zornitza Stark Gene: akr1c4 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.50 AKR1C4 Zornitza Stark Phenotypes for gene: AKR1C4 were changed from to {46XY sex reversal 8, modifier of}, MIM# 614279
Differences of Sex Development v0.49 AKR1C4 Zornitza Stark Publications for gene: AKR1C4 were set to
Differences of Sex Development v0.48 AKR1C4 Zornitza Stark Mode of inheritance for gene: AKR1C4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.47 AKR1C4 Zornitza Stark Classified gene: AKR1C4 as Red List (low evidence)
Differences of Sex Development v0.47 AKR1C4 Zornitza Stark Gene: akr1c4 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.46 AKR1C4 Zornitza Stark reviewed gene: AKR1C4: Rating: RED; Mode of pathogenicity: None; Publications: 21802064; Phenotypes: {46XY sex reversal 8, modifier of}, MIM# 614279; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.46 AKR1C2 Zornitza Stark Marked gene: AKR1C2 as ready
Differences of Sex Development v0.46 AKR1C2 Zornitza Stark Gene: akr1c2 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.46 AKR1C2 Zornitza Stark Phenotypes for gene: AKR1C2 were changed from to 46XY sex reversal 8, MIM# 614279
Differences of Sex Development v0.45 AKR1C2 Zornitza Stark Publications for gene: AKR1C2 were set to
Differences of Sex Development v0.44 AKR1C2 Zornitza Stark Mode of inheritance for gene: AKR1C2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.43 AKR1C2 Zornitza Stark Classified gene: AKR1C2 as Red List (low evidence)
Differences of Sex Development v0.43 AKR1C2 Zornitza Stark Gene: akr1c2 has been classified as Red List (Low Evidence).
Achromatopsia v0.18 Bryony Thompson Panel status changed from internal to public
Differences of Sex Development v0.42 AKR1C2 Zornitza Stark reviewed gene: AKR1C2: Rating: RED; Mode of pathogenicity: None; Publications: 21802064; Phenotypes: 46XY sex reversal 8, MIM# 614279; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2747 RPL10 Crystle Lee reviewed gene: RPL10: Rating: GREEN; Mode of pathogenicity: None; Publications: 25316788, 26290468, 25846674, 29066376; Phenotypes: Mental retardation, X-linked, syndromic, 35 (MIM#300998); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Differences of Sex Development v0.42 RPL10 Crystle Lee gene: RPL10 was added
gene: RPL10 was added to Disorders of Sex Differentiation. Sources: Expert Review
Mode of inheritance for gene: RPL10 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: RPL10 were set to 25316788; 26290468; 25846674; 29066376
Phenotypes for gene: RPL10 were set to Mental retardation, X-linked, syndromic, 35 (MIM#300998)
Review for gene: RPL10 was set to GREEN
Added comment: At least 3 variants have been reported. Urogenital anomalies are a feature of the associated condition.

PMID: 25316788: Variant reported in 3 members of a family. Genitourinary abnormalities (ie cryptorchidism) reported in all 3 affected individuals.

PMID: 26290468: Reported in a family with two affected cousins presenting with X-linked ID, cerebellar hypoplasia, and spondylo-epiphyseal dysplasia. Only one of the affected males presented with cryptorchidism.

PMID: 25846674: 3 of 4 affected males in the family presented with urogenital anomalies
Sources: Expert Review
Differences of Sex Development v0.42 SAMD9 Crystle Lee gene: SAMD9 was added
gene: SAMD9 was added to Disorders of Sex Differentiation. Sources: Expert Review
Mode of inheritance for gene: SAMD9 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SAMD9 were set to 27182967
Phenotypes for gene: SAMD9 were set to MIRAGE syndrome (MIM#617053)
Review for gene: SAMD9 was set to GREEN
Added comment: At least 10 families ( 8 diff variants) reported in one publication. External genital abnormalities observed in all 46, XY patients.
Sources: Expert Review
Differences of Sex Development v0.42 SEMA3E Crystle Lee gene: SEMA3E was added
gene: SEMA3E was added to Disorders of Sex Differentiation. Sources: Expert Review
Mode of inheritance for gene: SEMA3E was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SEMA3E were set to 25985275
Phenotypes for gene: SEMA3E were set to ?CHARGE syndrome (MIM#214800)
Review for gene: SEMA3E was set to RED
Added comment: Only one variant reported in 2 sibling with Kallman syndrome. Mouse model supports involvement of this gene with the phenotype. Variant not present in gnomad in homozygosity.
Sources: Expert Review
Arthrogryposis v0.186 ZIC3 Zornitza Stark Marked gene: ZIC3 as ready
Arthrogryposis v0.186 ZIC3 Zornitza Stark Gene: zic3 has been classified as Red List (Low Evidence).
Arthrogryposis v0.186 ZIC3 Zornitza Stark Phenotypes for gene: ZIC3 were changed from to Heterotaxy, visceral, 1, X-linked, MIM# 306955; VACTERL association, X-linked, MIM# 314390
Arthrogryposis v0.185 ZIC3 Zornitza Stark Mode of inheritance for gene: ZIC3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.184 ZIC3 Zornitza Stark Classified gene: ZIC3 as Red List (low evidence)
Arthrogryposis v0.184 ZIC3 Zornitza Stark Gene: zic3 has been classified as Red List (Low Evidence).
Arthrogryposis v0.183 ZIC3 Zornitza Stark reviewed gene: ZIC3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Heterotaxy, visceral, 1, X-linked, MIM# 306955, VACTERL association, X-linked, MIM# 314390; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Differences of Sex Development v0.42 SGPL1 Crystle Lee gene: SGPL1 was added
gene: SGPL1 was added to Disorders of Sex Differentiation. Sources: Expert Review
Mode of inheritance for gene: SGPL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SGPL1 were set to 28165339; 28165343; 28181337
Phenotypes for gene: SGPL1 were set to Nephrotic syndrome, type 14 (MIM#617575)
Review for gene: SGPL1 was set to GREEN
Added comment: >5 families reported. Cryptorchidism and hypogonadism are features of the associated phenotype.
Sources: Expert Review
Arthrogryposis v0.183 VAMP1 Zornitza Stark Marked gene: VAMP1 as ready
Arthrogryposis v0.183 VAMP1 Zornitza Stark Gene: vamp1 has been classified as Green List (High Evidence).
Arthrogryposis v0.183 VAMP1 Zornitza Stark Classified gene: VAMP1 as Green List (high evidence)
Arthrogryposis v0.183 VAMP1 Zornitza Stark Gene: vamp1 has been classified as Green List (High Evidence).
Arthrogryposis v0.182 VAMP1 Zornitza Stark gene: VAMP1 was added
gene: VAMP1 was added to Arthrogryposis. Sources: Expert list
Mode of inheritance for gene: VAMP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VAMP1 were set to 28253535
Phenotypes for gene: VAMP1 were set to Myasthenic syndrome, congenital, 25, MIM# 618323
Review for gene: VAMP1 was set to GREEN
Added comment: Severe neonatal hypotonia and joint laxity, though joint contractures described in some affected individuals.
Sources: Expert list
Arthrogryposis v0.181 UNC80 Zornitza Stark Marked gene: UNC80 as ready
Arthrogryposis v0.181 UNC80 Zornitza Stark Gene: unc80 has been classified as Red List (Low Evidence).
Arthrogryposis v0.181 UNC80 Zornitza Stark Phenotypes for gene: UNC80 were changed from to Hypotonia, infantile, with psychomotor retardation and characteristic facies 2, MIM# 616801
Arthrogryposis v0.180 UNC80 Zornitza Stark Publications for gene: UNC80 were set to
Arthrogryposis v0.179 UNC80 Zornitza Stark Mode of inheritance for gene: UNC80 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.178 UNC80 Zornitza Stark Classified gene: UNC80 as Red List (low evidence)
Arthrogryposis v0.178 UNC80 Zornitza Stark Gene: unc80 has been classified as Red List (Low Evidence).
Arthrogryposis v0.177 UNC80 Zornitza Stark reviewed gene: UNC80: Rating: RED; Mode of pathogenicity: None; Publications: 26545877, 26708753, 26708751; Phenotypes: Hypotonia, infantile, with psychomotor retardation and characteristic facies 2, MIM# 616801; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.362 SOX10 Crystle Lee reviewed gene: SOX10: Rating: GREEN; Mode of pathogenicity: None; Publications: 23643381, 24845202; Phenotypes: PCWH syndrome (MIM#609136), Waardenburg syndrome, type 2E, with or without neurologic involvement (MIM#611584), Waardenburg syndrome, type 4C (MIM#613266); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Differences of Sex Development v0.42 SOX10 Crystle Lee gene: SOX10 was added
gene: SOX10 was added to Disorders of Sex Differentiation. Sources: Expert Review
Mode of inheritance for gene: SOX10 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SOX10 were set to 23643381; 15004559
Phenotypes for gene: SOX10 were set to PCWH syndrome (MIM#609136); Waardenburg syndrome, type 2E, with or without neurologic involvement (MIM#611584); Waardenburg syndrome, type 4C (MIM#613266)
Mode of pathogenicity for gene: SOX10 was set to Other
Review for gene: SOX10 was set to GREEN
Added comment: Well reported gene disease association. Cryptorchidism and hypogonadism is a feature of Kallman Syndrome and WS4C

PMID: 23643381: Reported 6 variants in individuals with Kallman syndrome which is associated with hypogonadotropic hypogonadism. Functional studies performed.

PMID: 15004559: PCWH is caused by dominant-negative mutations (truncating variants) whereas NMD and thus haploinsufficiency results in WS4C
Sources: Expert Review
Arthrogryposis v0.177 TTN Zornitza Stark Marked gene: TTN as ready
Arthrogryposis v0.177 TTN Zornitza Stark Gene: ttn has been classified as Green List (High Evidence).
Arthrogryposis v0.177 TTN Zornitza Stark Classified gene: TTN as Green List (high evidence)
Arthrogryposis v0.177 TTN Zornitza Stark Gene: ttn has been classified as Green List (High Evidence).
Differences of Sex Development v0.42 TAC3 Crystle Lee reviewed gene: TAC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 19079066, 20332248, 23329188, 22031817; Phenotypes: Hypogonadotropic hypogonadism 10 with or without anosmia (MIM#614839); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.176 TTN Zornitza Stark gene: TTN was added
gene: TTN was added to Arthrogryposis. Sources: Expert list
Mode of inheritance for gene: TTN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTN were set to 24105469; 31660661; 29575618; 28040389
Phenotypes for gene: TTN were set to Salih myopathy; Muscular dystrophy, limb-girdle, autosomal recessive 10
Review for gene: TTN was set to GREEN
Added comment: By Sanger sequencing the TTN gene in 31 patients from 23 families segregating congenital core myopathy and primary heart disease, Chauveau et al. (2014) identified homozygous or compound heterozygous mutations in 5 patients from 4 families. The severity of the phenotype varied among the families. All 5 patients had congenital or infantile muscle weakness with axial and distal joint contractures and relatively preserved respiratory function. One individual presented with arthrogryposis, dislocated hips with dysplasia, and elbow, hip, and knee contractures.
Bryen et al: eight families with arthrogryposis multiplex congenita and myopathy bearing a TTN intron 213 extended splice-site variant (c.39974-11T>G), inherited in trans with a second pathogenic TTN variant.
Two families with AMC and biallelic truncating mutations in 29575618; 28040389.
Sources: Expert list
Arthrogryposis v0.175 TRIP4 Zornitza Stark reviewed gene: TRIP4: Rating: GREEN; Mode of pathogenicity: None; Publications: 26924529; Phenotypes: Spinal muscular atrophy with congenital bone fractures 1, MIM# 616866; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.42 TOE1 Crystle Lee gene: TOE1 was added
gene: TOE1 was added to Disorders of Sex Differentiation. Sources: Expert Review
Mode of inheritance for gene: TOE1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TOE1 were set to 28092684
Phenotypes for gene: TOE1 were set to Pontocerebellar hypoplasia, type 7 (MIM#614969)
Review for gene: TOE1 was set to GREEN
Added comment: >10 families with pontocerebellar hypoplasia type 7 (PCH7) reported with biallelic variants.MRI showed reduced cerebellar volume in these families. Ambiguous genitalia is a feature of this condition.
Sources: Expert Review
Cerebellar and Pontocerebellar Hypoplasia v0.140 TOE1 Crystle Lee reviewed gene: TOE1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28092684; Phenotypes: Pontocerebellar hypoplasia, type 7 (MIM#614969); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.42 TSPYL1 Crystle Lee reviewed gene: TSPYL1: Rating: AMBER; Mode of pathogenicity: None; Publications: 15273283, 19463995, 22137496, 25449952, 16418600; Phenotypes: Sudden infant death with dysgenesis of the testes syndrome (MIM#608800); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.175 TBX22 Zornitza Stark Marked gene: TBX22 as ready
Arthrogryposis v0.175 TBX22 Zornitza Stark Gene: tbx22 has been classified as Red List (Low Evidence).
Arthrogryposis v0.175 TBX22 Zornitza Stark Phenotypes for gene: TBX22 were changed from to Cleft palate with ankyloglossia, MIM# 303400
Arthrogryposis v0.174 TBX22 Zornitza Stark Classified gene: TBX22 as Red List (low evidence)
Arthrogryposis v0.174 TBX22 Zornitza Stark Gene: tbx22 has been classified as Red List (Low Evidence).
Arthrogryposis v0.173 TBX22 Zornitza Stark reviewed gene: TBX22: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Cleft palate with ankyloglossia, MIM# 303400; Mode of inheritance: None
Arthrogryposis v0.173 STAC3 Zornitza Stark Marked gene: STAC3 as ready
Arthrogryposis v0.173 STAC3 Zornitza Stark Gene: stac3 has been classified as Green List (High Evidence).
Arthrogryposis v0.173 STAC3 Zornitza Stark Classified gene: STAC3 as Green List (high evidence)
Arthrogryposis v0.173 STAC3 Zornitza Stark Gene: stac3 has been classified as Green List (High Evidence).
Arthrogryposis v0.172 STAC3 Zornitza Stark gene: STAC3 was added
gene: STAC3 was added to Arthrogryposis. Sources: Expert list
Mode of inheritance for gene: STAC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STAC3 were set to 23736855; 30168660; 28777491
Phenotypes for gene: STAC3 were set to Myopathy, congenital, Baily-Bloch, MIM# 255995
Review for gene: STAC3 was set to GREEN
Added comment: Arthrogryposis is part of the phenotype.
Sources: Expert list
Arthrogryposis v0.171 SMN1 Zornitza Stark Marked gene: SMN1 as ready
Arthrogryposis v0.171 SMN1 Zornitza Stark Gene: smn1 has been classified as Green List (High Evidence).
Arthrogryposis v0.171 SMN1 Zornitza Stark Classified gene: SMN1 as Green List (high evidence)
Arthrogryposis v0.171 SMN1 Zornitza Stark Gene: smn1 has been classified as Green List (High Evidence).
Arthrogryposis v0.170 SMN1 Zornitza Stark gene: SMN1 was added
gene: SMN1 was added to Arthrogryposis. Sources: Expert list
Mode of inheritance for gene: SMN1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SMN1 were set to Spinal muscular atrophy, type 0
Review for gene: SMN1 was set to GREEN
Added comment: Most severe end of the spectrum can present with arthrogryposis.
Sources: Expert list
Arthrogryposis v0.169 SLC9A6 Zornitza Stark Deleted their comment
Arthrogryposis v0.169 SLC9A6 Zornitza Stark commented on gene: SLC9A6: Contractures are reported but condition does not
Arthrogryposis v0.169 SLC9A6 Zornitza Stark Marked gene: SLC9A6 as ready
Arthrogryposis v0.169 SLC9A6 Zornitza Stark Gene: slc9a6 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.169 SLC9A6 Zornitza Stark Phenotypes for gene: SLC9A6 were changed from to Mental retardation, X-linked syndromic, Christianson type, MIM# 300243
Arthrogryposis v0.168 SLC9A6 Zornitza Stark Mode of inheritance for gene: SLC9A6 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.167 SLC9A6 Zornitza Stark Classified gene: SLC9A6 as Amber List (moderate evidence)
Arthrogryposis v0.167 SLC9A6 Zornitza Stark Gene: slc9a6 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.166 SLC9A6 Zornitza Stark reviewed gene: SLC9A6: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Mental retardation, X-linked syndromic, Christianson type, MIM# 300243; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.166 SLC6A9 Zornitza Stark Marked gene: SLC6A9 as ready
Arthrogryposis v0.166 SLC6A9 Zornitza Stark Gene: slc6a9 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.166 SLC6A9 Zornitza Stark Classified gene: SLC6A9 as Amber List (moderate evidence)
Arthrogryposis v0.166 SLC6A9 Zornitza Stark Gene: slc6a9 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.166 SLC6A9 Zornitza Stark Classified gene: SLC6A9 as Green List (high evidence)
Arthrogryposis v0.166 SLC6A9 Zornitza Stark Gene: slc6a9 has been classified as Green List (High Evidence).
Arthrogryposis v0.165 SLC6A9 Zornitza Stark gene: SLC6A9 was added
gene: SLC6A9 was added to Arthrogryposis. Sources: Expert list
Mode of inheritance for gene: SLC6A9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC6A9 were set to 27773429; 27481395
Phenotypes for gene: SLC6A9 were set to Glycine encephalopathy with normal serum glycine, MIM#617301; arthrogryposis
Review for gene: SLC6A9 was set to AMBER
Added comment: Two of the reported families have had arthrogryposis as a manifesting feature.
Sources: Expert list
Arthrogryposis v0.164 SLC18A3 Zornitza Stark Marked gene: SLC18A3 as ready
Arthrogryposis v0.164 SLC18A3 Zornitza Stark Gene: slc18a3 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.164 SLC18A3 Zornitza Stark Classified gene: SLC18A3 as Amber List (moderate evidence)
Arthrogryposis v0.164 SLC18A3 Zornitza Stark Gene: slc18a3 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.163 SLC18A3 Zornitza Stark gene: SLC18A3 was added
gene: SLC18A3 was added to Arthrogryposis. Sources: Expert list
Mode of inheritance for gene: SLC18A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC18A3 were set to 28188302; 27590285; 31059209
Phenotypes for gene: SLC18A3 were set to Myasthenic syndrome, congenital, 21, presynaptic, 617239; arthrogryposis
Review for gene: SLC18A3 was set to AMBER
Added comment: Two of four families presented with fetal akinesia and arthrogryposis.
Sources: Expert list
Arthrogryposis v0.162 RBM10 Zornitza Stark Marked gene: RBM10 as ready
Arthrogryposis v0.162 RBM10 Zornitza Stark Gene: rbm10 has been classified as Red List (Low Evidence).
Arthrogryposis v0.162 RBM10 Zornitza Stark Phenotypes for gene: RBM10 were changed from to TARP syndrome, MIM# 311900
Arthrogryposis v0.161 RBM10 Zornitza Stark Mode of inheritance for gene: RBM10 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.160 RBM10 Zornitza Stark Classified gene: RBM10 as Red List (low evidence)
Arthrogryposis v0.160 RBM10 Zornitza Stark Gene: rbm10 has been classified as Red List (Low Evidence).
Arthrogryposis v0.159 RBM10 Zornitza Stark reviewed gene: RBM10: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: TARP syndrome, MIM# 311900; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.3303 PIP5K1C Zornitza Stark Marked gene: PIP5K1C as ready
Mendeliome v0.3303 PIP5K1C Zornitza Stark Gene: pip5k1c has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3303 PIP5K1C Zornitza Stark Phenotypes for gene: PIP5K1C were changed from to Lethal congenital contractural syndrome 3, MIM# 611369
Mendeliome v0.3302 PIP5K1C Zornitza Stark Publications for gene: PIP5K1C were set to
Mendeliome v0.3301 PIP5K1C Zornitza Stark Mode of inheritance for gene: PIP5K1C was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3300 PIP5K1C Zornitza Stark Classified gene: PIP5K1C as Amber List (moderate evidence)
Mendeliome v0.3300 PIP5K1C Zornitza Stark Gene: pip5k1c has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3299 PIP5K1C Zornitza Stark reviewed gene: PIP5K1C: Rating: AMBER; Mode of pathogenicity: None; Publications: 17701898; Phenotypes: Lethal congenital contractural syndrome 3, MIM# 611369; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.159 PIP5K1C Zornitza Stark Marked gene: PIP5K1C as ready
Arthrogryposis v0.159 PIP5K1C Zornitza Stark Gene: pip5k1c has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.159 PIP5K1C Zornitza Stark Phenotypes for gene: PIP5K1C were changed from to Lethal congenital contractural syndrome 3, MIM# 611369
Arthrogryposis v0.158 PIP5K1C Zornitza Stark Publications for gene: PIP5K1C were set to
Arthrogryposis v0.157 PIP5K1C Zornitza Stark Mode of inheritance for gene: PIP5K1C was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.156 PIP5K1C Zornitza Stark Classified gene: PIP5K1C as Amber List (moderate evidence)
Arthrogryposis v0.156 PIP5K1C Zornitza Stark Gene: pip5k1c has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.155 PIP5K1C Zornitza Stark reviewed gene: PIP5K1C: Rating: AMBER; Mode of pathogenicity: None; Publications: 17701898; Phenotypes: Lethal congenital contractural syndrome 3, MIM# 611369; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.155 OFD1 Zornitza Stark Marked gene: OFD1 as ready
Arthrogryposis v0.155 OFD1 Zornitza Stark Gene: ofd1 has been classified as Red List (Low Evidence).
Arthrogryposis v0.155 OFD1 Zornitza Stark Phenotypes for gene: OFD1 were changed from to Joubert syndrome 10, MIM# 300804; Orofaciodigital syndrome I, MIM# 311200; Simpson-Golabi-Behmel syndrome, type 2, MIM# 300209
Arthrogryposis v0.154 OFD1 Zornitza Stark Publications for gene: OFD1 were set to
Arthrogryposis v0.153 OFD1 Zornitza Stark Mode of inheritance for gene: OFD1 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Arthrogryposis v0.152 OFD1 Zornitza Stark Classified gene: OFD1 as Red List (low evidence)
Arthrogryposis v0.152 OFD1 Zornitza Stark Gene: ofd1 has been classified as Red List (Low Evidence).
Arthrogryposis v0.151 OFD1 Zornitza Stark reviewed gene: OFD1: Rating: RED; Mode of pathogenicity: None; Publications: 20301367; Phenotypes: Joubert syndrome 10, MIM# 300804, Orofaciodigital syndrome I, MIM# 311200, Simpson-Golabi-Behmel syndrome, type 2, MIM# 300209; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Arthrogryposis v0.151 MYMK Zornitza Stark Marked gene: MYMK as ready
Arthrogryposis v0.151 MYMK Zornitza Stark Gene: mymk has been classified as Green List (High Evidence).
Arthrogryposis v0.151 MYMK Zornitza Stark Classified gene: MYMK as Green List (high evidence)
Arthrogryposis v0.151 MYMK Zornitza Stark Gene: mymk has been classified as Green List (High Evidence).
Arthrogryposis v0.150 MYMK Zornitza Stark gene: MYMK was added
gene: MYMK was added to Arthrogryposis. Sources: Expert list
Mode of inheritance for gene: MYMK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYMK were set to 28681861
Phenotypes for gene: MYMK were set to Carey-Fineman-Ziter syndrome 254940
Review for gene: MYMK was set to GREEN
Added comment: Distal contractures are part of the phenotype of this muscle disorder.
Sources: Expert list
Arthrogryposis v0.149 MYL1 Zornitza Stark Marked gene: MYL1 as ready
Arthrogryposis v0.149 MYL1 Zornitza Stark Gene: myl1 has been classified as Red List (Low Evidence).
Arthrogryposis v0.149 MYL1 Zornitza Stark gene: MYL1 was added
gene: MYL1 was added to Arthrogryposis. Sources: Expert list
Mode of inheritance for gene: MYL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYL1 were set to 30215711
Phenotypes for gene: MYL1 were set to Myopathy, congenital, with fast-twitch (type II) fiber atrophy, MIM# 618414
Review for gene: MYL1 was set to RED
Added comment: Two families and a zebrafish model. Predominant finding is that of hypotonia, mild contractures reported in one.
Sources: Expert list
Arthrogryposis v0.148 MED12 Zornitza Stark reviewed gene: MED12: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301719; Phenotypes: MED12-related disorders; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.148 MAGEL2 Zornitza Stark Marked gene: MAGEL2 as ready
Arthrogryposis v0.148 MAGEL2 Zornitza Stark Gene: magel2 has been classified as Green List (High Evidence).
Arthrogryposis v0.148 MAGEL2 Zornitza Stark Classified gene: MAGEL2 as Green List (high evidence)
Arthrogryposis v0.148 MAGEL2 Zornitza Stark Gene: magel2 has been classified as Green List (High Evidence).
Arthrogryposis v0.147 MAGEL2 Zornitza Stark gene: MAGEL2 was added
gene: MAGEL2 was added to Arthrogryposis. Sources: Expert list
Mode of inheritance for gene: MAGEL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAGEL2 were set to 24076603; 27195816; 26365340
Phenotypes for gene: MAGEL2 were set to Schaaf-Yang syndrome
Review for gene: MAGEL2 was set to GREEN
Added comment: Fountain et al. (2017) reported 18 patients with SHFYNG ascertained on the basis of genetic studies from several different research groups or laboratories. Joint contractures were present in almost all patients, and ranged from only the interphalangeal joints to lethal fetal akinesia with severe arthrogryposis.
Mejlachowicz et al (2015) reported two unrelated families with lethal AMC and heterozygous truncating frameshift MAGEL2 mutations on paternal allele.
Sources: Expert list
Arthrogryposis v0.146 LMX1B Zornitza Stark Marked gene: LMX1B as ready
Arthrogryposis v0.146 LMX1B Zornitza Stark Gene: lmx1b has been classified as Green List (High Evidence).
Arthrogryposis v0.146 LMX1B Zornitza Stark Classified gene: LMX1B as Green List (high evidence)
Arthrogryposis v0.146 LMX1B Zornitza Stark Gene: lmx1b has been classified as Green List (High Evidence).
Arthrogryposis v0.145 LMX1B Zornitza Stark gene: LMX1B was added
gene: LMX1B was added to Arthrogryposis. Sources: Expert list
Mode of inheritance for gene: LMX1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: LMX1B were set to Nail-patella syndrome, MIM# 161200
Review for gene: LMX1B was set to GREEN
Added comment: Elbow and knee contractures are common features.
Sources: Expert list
Arthrogryposis v0.144 L1CAM Zornitza Stark Marked gene: L1CAM as ready
Arthrogryposis v0.144 L1CAM Zornitza Stark Gene: l1cam has been classified as Red List (Low Evidence).
Arthrogryposis v0.144 L1CAM Zornitza Stark Phenotypes for gene: L1CAM were changed from to Hydrocephalus due to aqueductal stenosis 307000
Arthrogryposis v0.143 L1CAM Zornitza Stark Publications for gene: L1CAM were set to
Arthrogryposis v0.142 L1CAM Zornitza Stark Mode of inheritance for gene: L1CAM was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.141 L1CAM Zornitza Stark Classified gene: L1CAM as Red List (low evidence)
Arthrogryposis v0.141 L1CAM Zornitza Stark Gene: l1cam has been classified as Red List (Low Evidence).
Arthrogryposis v0.140 L1CAM Zornitza Stark reviewed gene: L1CAM: Rating: RED; Mode of pathogenicity: None; Publications: 31504653; Phenotypes: Hydrocephalus due to aqueductal stenosis 307000; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.140 GPC3 Zornitza Stark Marked gene: GPC3 as ready
Arthrogryposis v0.140 GPC3 Zornitza Stark Gene: gpc3 has been classified as Red List (Low Evidence).
Arthrogryposis v0.140 GPC3 Zornitza Stark Phenotypes for gene: GPC3 were changed from to Simpson-Golabi-Behmel syndrome, type 1, MIM# 312870
Arthrogryposis v0.139 GPC3 Zornitza Stark Publications for gene: GPC3 were set to
Arthrogryposis v0.138 GPC3 Zornitza Stark Mode of inheritance for gene: GPC3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.137 GPC3 Zornitza Stark Classified gene: GPC3 as Red List (low evidence)
Arthrogryposis v0.137 GPC3 Zornitza Stark Gene: gpc3 has been classified as Red List (Low Evidence).
Arthrogryposis v0.136 GPC3 Zornitza Stark reviewed gene: GPC3: Rating: RED; Mode of pathogenicity: None; Publications: 20301398; Phenotypes: Simpson-Golabi-Behmel syndrome, type 1, MIM# 312870; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.136 FLNA Zornitza Stark Marked gene: FLNA as ready
Arthrogryposis v0.136 FLNA Zornitza Stark Gene: flna has been classified as Green List (High Evidence).
Arthrogryposis v0.136 FLNA Zornitza Stark Phenotypes for gene: FLNA were changed from to FLNA-related disorders; Otopalatodigital syndrome, type I 311300; Otopalatodigital syndrome, type II 304120; Terminal osseous dysplasia 300244
Arthrogryposis v0.135 FLNA Zornitza Stark Publications for gene: FLNA were set to
Arthrogryposis v0.134 FLNA Zornitza Stark Mode of inheritance for gene: FLNA 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)
Arthrogryposis v0.134 FLNA Zornitza Stark Mode of inheritance for gene: FLNA was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.133 FLNA Zornitza Stark reviewed gene: FLNA: Rating: GREEN; Mode of pathogenicity: None; Publications: 26804200, 30561107, 20301567; Phenotypes: FLNA-related disorders, Otopalatodigital syndrome, type I 311300, Otopalatodigital syndrome, type II 304120, Terminal osseous dysplasia 300244; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Arthrogryposis v0.132 FHL1 Zornitza Stark Marked gene: FHL1 as ready
Arthrogryposis v0.132 FHL1 Zornitza Stark Gene: fhl1 has been classified as Red List (Low Evidence).
Arthrogryposis v0.132 FHL1 Zornitza Stark Phenotypes for gene: FHL1 were changed from to Emery-Dreifuss muscular dystrophy 6, X-linked, MIM# 300696; Myopathy, X-linked, with postural muscle atrophy, MIM# 300696; Reducing body myopathy, X-linked 1a, severe, infantile or early childhood onset, MIM# 300717; Reducing body myopathy, X-linked 1b, with late childhood or adult onset, MIM# 300718; Scapuloperoneal myopathy, X-linked dominant, MIM# 300695
Arthrogryposis v0.131 FHL1 Zornitza Stark Mode of inheritance for gene: FHL1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.130 FHL1 Zornitza Stark Classified gene: FHL1 as Red List (low evidence)
Arthrogryposis v0.130 FHL1 Zornitza Stark Gene: fhl1 has been classified as Red List (Low Evidence).
Arthrogryposis v0.129 FHL1 Zornitza Stark reviewed gene: FHL1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Emery-Dreifuss muscular dystrophy 6, X-linked, MIM# 300696, Myopathy, X-linked, with postural muscle atrophy, MIM# 300696, Reducing body myopathy, X-linked 1a, severe, infantile or early childhood onset, MIM# 300717, Reducing body myopathy, X-linked 1b, with late childhood or adult onset, MIM# 300718, Scapuloperoneal myopathy, X-linked dominant, MIM# 300695; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.129 FGD1 Zornitza Stark Marked gene: FGD1 as ready
Arthrogryposis v0.129 FGD1 Zornitza Stark Gene: fgd1 has been classified as Red List (Low Evidence).
Arthrogryposis v0.129 FGD1 Zornitza Stark Phenotypes for gene: FGD1 were changed from to Aarskog-Scott syndrome, MIM# 305400; Mental retardation, X-linked syndromic 16, MIM# 305400
Arthrogryposis v0.128 FGD1 Zornitza Stark Publications for gene: FGD1 were set to
Arthrogryposis v0.127 FGD1 Zornitza Stark Mode of inheritance for gene: FGD1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.126 FGD1 Zornitza Stark Classified gene: FGD1 as Red List (low evidence)
Arthrogryposis v0.126 FGD1 Zornitza Stark Gene: fgd1 has been classified as Red List (Low Evidence).
Arthrogryposis v0.125 FGD1 Zornitza Stark reviewed gene: FGD1: Rating: RED; Mode of pathogenicity: None; Publications: 27551683; Phenotypes: Aarskog-Scott syndrome, MIM# 305400, Mental retardation, X-linked syndromic 16 305400; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.125 ERCC5 Zornitza Stark Classified gene: ERCC5 as Green List (high evidence)
Arthrogryposis v0.125 ERCC5 Zornitza Stark Gene: ercc5 has been classified as Green List (High Evidence).
Arthrogryposis v0.124 ERCC5 Zornitza Stark edited their review of gene: ERCC5: Changed publications: 24700531, 32557569
Arthrogryposis v0.124 ERCC5 Zornitza Stark changed review comment from: Single family reported with 5 affected fetuses and severe COFS including arthrogryposis.
Sources: Expert list; to: A family reported with 5 affected fetuses and severe COFS including arthrogryposis in PMID:24700531. Further two included in a recent review of severe neonatal presentations of nucleotide excision-repair disorders (PMID:32557569).
Sources: Expert list
Arthrogryposis v0.124 ERCC5 Zornitza Stark edited their review of gene: ERCC5: Changed rating: GREEN
Arthrogryposis v0.124 ERCC5 Zornitza Stark Marked gene: ERCC5 as ready
Arthrogryposis v0.124 ERCC5 Zornitza Stark Gene: ercc5 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.124 ERCC5 Zornitza Stark Classified gene: ERCC5 as Amber List (moderate evidence)
Arthrogryposis v0.124 ERCC5 Zornitza Stark Gene: ercc5 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.123 ERCC5 Zornitza Stark gene: ERCC5 was added
gene: ERCC5 was added to Arthrogryposis. Sources: Expert list
Mode of inheritance for gene: ERCC5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERCC5 were set to 24700531
Phenotypes for gene: ERCC5 were set to Cerebrooculofacioskeletal syndrome 3, MIM# 616570
Review for gene: ERCC5 was set to AMBER
Added comment: Single family reported with 5 affected fetuses and severe COFS including arthrogryposis.
Sources: Expert list
Mendeliome v0.3299 ERBB3 Zornitza Stark Marked gene: ERBB3 as ready
Mendeliome v0.3299 ERBB3 Zornitza Stark Gene: erbb3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3299 ERBB3 Zornitza Stark Phenotypes for gene: ERBB3 were changed from to Lethal congenital contractural syndrome 2, MIM# 607598
Mendeliome v0.3298 ERBB3 Zornitza Stark Publications for gene: ERBB3 were set to
Mendeliome v0.3297 ERBB3 Zornitza Stark Mode of inheritance for gene: ERBB3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3296 ERBB3 Zornitza Stark Classified gene: ERBB3 as Amber List (moderate evidence)
Mendeliome v0.3296 ERBB3 Zornitza Stark Gene: erbb3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3295 ERBB3 Zornitza Stark reviewed gene: ERBB3: Rating: AMBER; Mode of pathogenicity: None; Publications: 17701904, 31752936; Phenotypes: Lethal congenital contractural syndrome 2, MIM# 607598; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.122 ERBB3 Zornitza Stark Marked gene: ERBB3 as ready
Arthrogryposis v0.122 ERBB3 Zornitza Stark Gene: erbb3 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.122 ERBB3 Zornitza Stark Phenotypes for gene: ERBB3 were changed from to Lethal congenital contractural syndrome 2, MIM# 607598
Arthrogryposis v0.121 ERBB3 Zornitza Stark Publications for gene: ERBB3 were set to
Arthrogryposis v0.120 ERBB3 Zornitza Stark Mode of inheritance for gene: ERBB3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.119 ERBB3 Zornitza Stark Classified gene: ERBB3 as Amber List (moderate evidence)
Arthrogryposis v0.119 ERBB3 Zornitza Stark Gene: erbb3 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.118 ERBB3 Zornitza Stark reviewed gene: ERBB3: Rating: AMBER; Mode of pathogenicity: None; Publications: 17701904, 31752936; Phenotypes: Lethal congenital contractural syndrome 2, MIM# 607598; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.118 EIF2S3 Zornitza Stark Marked gene: EIF2S3 as ready
Arthrogryposis v0.118 EIF2S3 Zornitza Stark Gene: eif2s3 has been classified as Red List (Low Evidence).
Arthrogryposis v0.118 EIF2S3 Zornitza Stark Phenotypes for gene: EIF2S3 were changed from to MEHMO syndrome, MIM# 300148
Arthrogryposis v0.117 EIF2S3 Zornitza Stark Publications for gene: EIF2S3 were set to
Arthrogryposis v0.116 EIF2S3 Zornitza Stark Mode of inheritance for gene: EIF2S3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.115 EIF2S3 Zornitza Stark Classified gene: EIF2S3 as Red List (low evidence)
Arthrogryposis v0.115 EIF2S3 Zornitza Stark Gene: eif2s3 has been classified as Red List (Low Evidence).
Arthrogryposis v0.114 EIF2S3 Zornitza Stark reviewed gene: EIF2S3: Rating: RED; Mode of pathogenicity: None; Publications: 23063529, 27333055, 28055140; Phenotypes: MEHMO syndrome, MIM# 300148; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.114 EBP Zornitza Stark Publications for gene: EBP were set to 21634086
Arthrogryposis v0.113 EBP Zornitza Stark edited their review of gene: EBP: Changed publications: 21634086, 24704792
Arthrogryposis v0.113 EBP Zornitza Stark Marked gene: EBP as ready
Arthrogryposis v0.113 EBP Zornitza Stark Gene: ebp has been classified as Green List (High Evidence).
Arthrogryposis v0.113 EBP Zornitza Stark Phenotypes for gene: EBP were changed from to Chondrodysplasia punctata, X-linked dominant, MIM# 302960
Arthrogryposis v0.112 EBP Zornitza Stark Publications for gene: EBP were set to
Arthrogryposis v0.111 EBP Zornitza Stark Mode of inheritance for gene: EBP was changed from Unknown to Other
Arthrogryposis v0.110 EBP Zornitza Stark reviewed gene: EBP: Rating: GREEN; Mode of pathogenicity: None; Publications: 21634086; Phenotypes: Chondrodysplasia punctata, X-linked dominant, MIM# 302960; Mode of inheritance: Other
Arthrogryposis v0.110 DYNC1H1 Zornitza Stark Marked gene: DYNC1H1 as ready
Arthrogryposis v0.110 DYNC1H1 Zornitza Stark Gene: dync1h1 has been classified as Green List (High Evidence).
Arthrogryposis v0.110 DYNC1H1 Zornitza Stark Classified gene: DYNC1H1 as Green List (high evidence)
Arthrogryposis v0.110 DYNC1H1 Zornitza Stark Gene: dync1h1 has been classified as Green List (High Evidence).
Arthrogryposis v0.109 DYNC1H1 Zornitza Stark gene: DYNC1H1 was added
gene: DYNC1H1 was added to Arthrogryposis. Sources: Expert list
Mode of inheritance for gene: DYNC1H1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DYNC1H1 were set to 25609763; 25512093; 28554554
Phenotypes for gene: DYNC1H1 were set to Charcot-Marie-Tooth disease, axonal, type 20, MIM# 614228; Mental retardation, autosomal dominant 13, MIM# 614563; Spinal muscular atrophy, lower extremity-predominant 1, MIM# 158600
Review for gene: DYNC1H1 was set to GREEN
Added comment: Phenotypes associated with DYNC1H1 range from spinal muscular atrophy (SMA), hereditary motor and sensory neuropathy (HMSN), cortical malformations, or a combination of these. Multiple families reported where arthrogryposis is a prominent feature.
Sources: Expert list
Mendeliome v0.3295 DPM2 Zornitza Stark Marked gene: DPM2 as ready
Mendeliome v0.3295 DPM2 Zornitza Stark Gene: dpm2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3295 DPM2 Zornitza Stark Phenotypes for gene: DPM2 were changed from to Congenital disorder of glycosylation, type Iu, MIM# 615042
Mendeliome v0.3294 DPM2 Zornitza Stark Publications for gene: DPM2 were set to
Mendeliome v0.3293 DPM2 Zornitza Stark Mode of inheritance for gene: DPM2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3292 DPM2 Zornitza Stark Classified gene: DPM2 as Amber List (moderate evidence)
Mendeliome v0.3292 DPM2 Zornitza Stark Gene: dpm2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3291 DPM2 Zornitza Stark reviewed gene: DPM2: Rating: AMBER; Mode of pathogenicity: None; Publications: 23109149; Phenotypes: Congenital disorder of glycosylation, type Iu, MIM# 615042; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.59 DPM2 Zornitza Stark Marked gene: DPM2 as ready
Muscular dystrophy and myopathy_Paediatric v0.59 DPM2 Zornitza Stark Gene: dpm2 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v0.59 DPM2 Zornitza Stark Phenotypes for gene: DPM2 were changed from to Congenital disorder of glycosylation, type Iu, MIM# 615042
Muscular dystrophy and myopathy_Paediatric v0.58 DPM2 Zornitza Stark Publications for gene: DPM2 were set to
Muscular dystrophy and myopathy_Paediatric v0.57 DPM2 Zornitza Stark Mode of inheritance for gene: DPM2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.56 DPM2 Zornitza Stark Classified gene: DPM2 as Amber List (moderate evidence)
Muscular dystrophy and myopathy_Paediatric v0.56 DPM2 Zornitza Stark Gene: dpm2 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v0.55 DPM2 Zornitza Stark reviewed gene: DPM2: Rating: AMBER; Mode of pathogenicity: None; Publications: 23109149; Phenotypes: Congenital disorder of glycosylation, type Iu, MIM# 615042; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.57 DPM2 Zornitza Stark Marked gene: DPM2 as ready
Congenital Disorders of Glycosylation v0.57 DPM2 Zornitza Stark Gene: dpm2 has been classified as Amber List (Moderate Evidence).
Congenital Disorders of Glycosylation v0.57 DPM2 Zornitza Stark Phenotypes for gene: DPM2 were changed from to Congenital disorder of glycosylation, type Iu, MIM#615042
Congenital Disorders of Glycosylation v0.56 DPM2 Zornitza Stark Publications for gene: DPM2 were set to
Congenital Disorders of Glycosylation v0.55 DPM2 Zornitza Stark Mode of inheritance for gene: DPM2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.54 DPM2 Zornitza Stark Classified gene: DPM2 as Amber List (moderate evidence)
Congenital Disorders of Glycosylation v0.54 DPM2 Zornitza Stark Gene: dpm2 has been classified as Amber List (Moderate Evidence).
Congenital Disorders of Glycosylation v0.53 DPM2 Zornitza Stark reviewed gene: DPM2: Rating: AMBER; Mode of pathogenicity: None; Publications: 23109149; Phenotypes: Congenital disorder of glycosylation, type Iu, MIM#615042; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.108 DPM2 Zornitza Stark Marked gene: DPM2 as ready
Arthrogryposis v0.108 DPM2 Zornitza Stark Gene: dpm2 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.108 DPM2 Zornitza Stark Phenotypes for gene: DPM2 were changed from to Congenital disorder of glycosylation, type Iu, MIM# 615042
Arthrogryposis v0.107 DPM2 Zornitza Stark Publications for gene: DPM2 were set to
Arthrogryposis v0.106 DPM2 Zornitza Stark Mode of inheritance for gene: DPM2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.105 DPM2 Zornitza Stark Classified gene: DPM2 as Amber List (moderate evidence)
Arthrogryposis v0.105 DPM2 Zornitza Stark Gene: dpm2 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.104 DPM2 Zornitza Stark reviewed gene: DPM2: Rating: AMBER; Mode of pathogenicity: None; Publications: 23109149; Phenotypes: Congenital disorder of glycosylation, type Iu, MIM# 615042; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.104 DPAGT1 Zornitza Stark Marked gene: DPAGT1 as ready
Arthrogryposis v0.104 DPAGT1 Zornitza Stark Gene: dpagt1 has been classified as Green List (High Evidence).
Arthrogryposis v0.104 DPAGT1 Zornitza Stark Classified gene: DPAGT1 as Green List (high evidence)
Arthrogryposis v0.104 DPAGT1 Zornitza Stark Gene: dpagt1 has been classified as Green List (High Evidence).
Arthrogryposis v0.103 DPAGT1 Zornitza Stark gene: DPAGT1 was added
gene: DPAGT1 was added to Arthrogryposis. Sources: Expert list
Mode of inheritance for gene: DPAGT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DPAGT1 were set to 26033833; 22786653; 30653653; 22492991
Phenotypes for gene: DPAGT1 were set to Congenital disorder of glycosylation, type Ij; Myasthenic syndrome, congenital, 13, with tubular aggregates 614750
Review for gene: DPAGT1 was set to GREEN
Added comment: Fetal akinesia and AMC.
Sources: Expert list
Arthrogryposis v0.102 DHCR24 Zornitza Stark Marked gene: DHCR24 as ready
Arthrogryposis v0.102 DHCR24 Zornitza Stark Gene: dhcr24 has been classified as Green List (High Evidence).
Arthrogryposis v0.102 DHCR24 Zornitza Stark Classified gene: DHCR24 as Green List (high evidence)
Arthrogryposis v0.102 DHCR24 Zornitza Stark Gene: dhcr24 has been classified as Green List (High Evidence).
Arthrogryposis v0.101 DHCR24 Zornitza Stark gene: DHCR24 was added
gene: DHCR24 was added to Arthrogryposis. Sources: Expert list
Mode of inheritance for gene: DHCR24 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DHCR24 were set to 21671375; 12457401; 29175559; 21559050
Phenotypes for gene: DHCR24 were set to Desmosterolosis, MIM# 602398
Review for gene: DHCR24 was set to GREEN
Added comment: At least 4 families reported where contractures are a feature of the condition.
Sources: Expert list
Arthrogryposis v0.100 DCX Zornitza Stark Marked gene: DCX as ready
Arthrogryposis v0.100 DCX Zornitza Stark Gene: dcx has been classified as Red List (Low Evidence).
Arthrogryposis v0.100 DCX Zornitza Stark Phenotypes for gene: DCX were changed from to Lissencephaly, X-linked, MIM# 300067
Arthrogryposis v0.99 DCX Zornitza Stark Publications for gene: DCX were set to
Arthrogryposis v0.98 DCX Zornitza Stark Mode of inheritance for gene: DCX was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.97 DCX Zornitza Stark Classified gene: DCX as Red List (low evidence)
Arthrogryposis v0.97 DCX Zornitza Stark Gene: dcx has been classified as Red List (Low Evidence).
Arthrogryposis v0.96 DCX Zornitza Stark reviewed gene: DCX: Rating: RED; Mode of pathogenicity: None; Publications: 20301364; Phenotypes: Lissencephaly, X-linked, MIM# 300067; Mode of inheritance: None
Cerebellar and Pontocerebellar Hypoplasia v0.140 COASY Zornitza Stark Classified gene: COASY as Amber List (moderate evidence)
Cerebellar and Pontocerebellar Hypoplasia v0.140 COASY Zornitza Stark Gene: coasy has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.96 COASY Zornitza Stark Marked gene: COASY as ready
Arthrogryposis v0.96 COASY Zornitza Stark Gene: coasy has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.96 COASY Zornitza Stark Classified gene: COASY as Amber List (moderate evidence)
Arthrogryposis v0.96 COASY Zornitza Stark Gene: coasy has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.95 COASY Zornitza Stark gene: COASY was added
gene: COASY was added to Arthrogryposis. Sources: Expert list
Mode of inheritance for gene: COASY was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COASY were set to 30089828
Phenotypes for gene: COASY were set to Pontocerebellar hypoplasia; microcephaly; arthrogryposis
Review for gene: COASY was set to AMBER
Added comment: Two families reported with a severe, prenatal onset phenotype comprising PCH, microcephaly and arthrogryposis. Note gene is also associated with NBIA.
Sources: Expert list
Arthrogryposis v0.94 CASK Zornitza Stark Marked gene: CASK as ready
Arthrogryposis v0.94 CASK Zornitza Stark Gene: cask has been classified as Red List (Low Evidence).
Arthrogryposis v0.94 CASK Zornitza Stark Phenotypes for gene: CASK were changed from to FG syndrome 4, MIM# 300422; Mental retardation, with or without nystagmus, MIM# 300422
Arthrogryposis v0.93 CASK Zornitza Stark Publications for gene: CASK were set to
Arthrogryposis v0.92 CASK Zornitza Stark Mode of inheritance for gene: CASK was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.91 CASK Zornitza Stark Classified gene: CASK as Red List (low evidence)
Arthrogryposis v0.91 CASK Zornitza Stark Gene: cask has been classified as Red List (Low Evidence).
Arthrogryposis v0.90 CASK Zornitza Stark reviewed gene: CASK: Rating: RED; Mode of pathogenicity: None; Publications: 24278995; Phenotypes: FG syndrome 4, MIM# 300422, Mental retardation, with or without nystagmus, MIM# 300422; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.90 ATRX Zornitza Stark Marked gene: ATRX as ready
Arthrogryposis v0.90 ATRX Zornitza Stark Gene: atrx has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.90 ATRX Zornitza Stark Phenotypes for gene: ATRX were changed from to Alpha-thalassemia/mental retardation syndrome, MIM# 301040
Arthrogryposis v0.89 ATRX Zornitza Stark Publications for gene: ATRX were set to
Arthrogryposis v0.88 ATRX Zornitza Stark Mode of inheritance for gene: ATRX was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.87 ATRX Zornitza Stark Classified gene: ATRX as Amber List (moderate evidence)
Arthrogryposis v0.87 ATRX Zornitza Stark Gene: atrx has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.86 ATRX Zornitza Stark reviewed gene: ATRX: Rating: AMBER; Mode of pathogenicity: None; Publications: 20301622; Phenotypes: Alpha-thalassemia/mental retardation syndrome, MIM# 301040; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.86 ATP1A2 Zornitza Stark Classified gene: ATP1A2 as Green List (high evidence)
Arthrogryposis v0.86 ATP1A2 Zornitza Stark Gene: atp1a2 has been classified as Green List (High Evidence).
Arthrogryposis v0.85 ATP1A2 Zornitza Stark changed review comment from: 3 newborns from 2 unrelated families who died neontally, presenting in utero with fetal hydrops, seizures and polyhydramnios. At birth they had arthrogryposis, microcephaly, malformations of cortical development, dysmorphic features and severe respiratory insufficiency. Biallelic LOF variants in ATP1A2 were found on WES. Note mono allelic variants in this gene cause alternating hemiplegia/migraine phenotypes.
Sources: Expert list; to: 3 newborns from 2 unrelated families who died neontally, presenting in utero with fetal hydrops, seizures and polyhydramnios. At birth they had arthrogryposis, microcephaly, malformations of cortical development, dysmorphic features and severe respiratory insufficiency. Biallelic LOF variants in ATP1A2 were found on WES. Mouse model is perinatal lethal. Note mono allelic variants in this gene cause alternating hemiplegia/migraine phenotypes.
Sources: Expert list
Arthrogryposis v0.85 ATP1A2 Zornitza Stark edited their review of gene: ATP1A2: Changed rating: GREEN
Arthrogryposis v0.85 ATP1A2 Zornitza Stark Marked gene: ATP1A2 as ready
Arthrogryposis v0.85 ATP1A2 Zornitza Stark Gene: atp1a2 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.85 ATP1A2 Zornitza Stark Classified gene: ATP1A2 as Amber List (moderate evidence)
Arthrogryposis v0.85 ATP1A2 Zornitza Stark Gene: atp1a2 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.84 ATP1A2 Zornitza Stark gene: ATP1A2 was added
gene: ATP1A2 was added to Arthrogryposis. Sources: Expert list
Mode of inheritance for gene: ATP1A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP1A2 were set to 30690204
Phenotypes for gene: ATP1A2 were set to hydrops; arthrogryposis; microcephaly; malformations of cortical development; dysmorphic features; severe respiratory insufficiency
Review for gene: ATP1A2 was set to AMBER
Added comment: 3 newborns from 2 unrelated families who died neontally, presenting in utero with fetal hydrops, seizures and polyhydramnios. At birth they had arthrogryposis, microcephaly, malformations of cortical development, dysmorphic features and severe respiratory insufficiency. Biallelic LOF variants in ATP1A2 were found on WES. Note mono allelic variants in this gene cause alternating hemiplegia/migraine phenotypes.
Sources: Expert list
Arthrogryposis v0.83 ATAD1 Zornitza Stark Marked gene: ATAD1 as ready
Arthrogryposis v0.83 ATAD1 Zornitza Stark Gene: atad1 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.83 ATAD1 Zornitza Stark Classified gene: ATAD1 as Amber List (moderate evidence)
Arthrogryposis v0.83 ATAD1 Zornitza Stark Gene: atad1 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.82 ATAD1 Zornitza Stark gene: ATAD1 was added
gene: ATAD1 was added to Arthrogryposis. Sources: Expert list
Mode of inheritance for gene: ATAD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATAD1 were set to 29659736; 29390050; 28180185
Phenotypes for gene: ATAD1 were set to Hyperekplexia 4, MIM# 618011
Review for gene: ATAD1 was set to AMBER
Added comment: At least one family where arthrogryposis was a prominent manifestation of this neurological condition.
Sources: Expert list
Arthrogryposis v0.81 ARX Zornitza Stark Marked gene: ARX as ready
Arthrogryposis v0.81 ARX Zornitza Stark Gene: arx has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.81 ARX Zornitza Stark Phenotypes for gene: ARX were changed from to Epileptic encephalopathy, early infantile, 1 308350; Hydranencephaly with abnormal genitalia 300215; Lissencephaly, X-linked 2 300215; Mental retardation, X-linked 29 and others 300419; Partington syndrome 309510; Proud syndrome 300004
Arthrogryposis v0.80 ARX Zornitza Stark Publications for gene: ARX were set to
Arthrogryposis v0.79 ARX Zornitza Stark Mode of inheritance for gene: ARX was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.78 ARX Zornitza Stark Classified gene: ARX as Amber List (moderate evidence)
Arthrogryposis v0.78 ARX Zornitza Stark Gene: arx has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.77 ARX Zornitza Stark reviewed gene: ARX: Rating: AMBER; Mode of pathogenicity: None; Publications: 21416597; Phenotypes: Epileptic encephalopathy, early infantile, 1 308350, Hydranencephaly with abnormal genitalia 300215, Lissencephaly, X-linked 2 300215, Mental retardation, X-linked 29 and others 300419, Partington syndrome 309510, Proud syndrome 300004; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.77 AP1S2 Zornitza Stark Marked gene: AP1S2 as ready
Arthrogryposis v0.77 AP1S2 Zornitza Stark Gene: ap1s2 has been classified as Red List (Low Evidence).
Arthrogryposis v0.77 AP1S2 Zornitza Stark Phenotypes for gene: AP1S2 were changed from to Mental retardation, X-linked syndromic 5, MIM# 304340
Arthrogryposis v0.76 AP1S2 Zornitza Stark Publications for gene: AP1S2 were set to
Arthrogryposis v0.75 AP1S2 Zornitza Stark Mode of inheritance for gene: AP1S2 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.74 AP1S2 Zornitza Stark Classified gene: AP1S2 as Red List (low evidence)
Arthrogryposis v0.74 AP1S2 Zornitza Stark Gene: ap1s2 has been classified as Red List (Low Evidence).
Arthrogryposis v0.73 AP1S2 Zornitza Stark reviewed gene: AP1S2: Rating: RED; Mode of pathogenicity: None; Publications: 30714330; Phenotypes: Mental retardation, X-linked syndromic 5, MIM# 304340; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.73 ALG3 Zornitza Stark Marked gene: ALG3 as ready
Arthrogryposis v0.73 ALG3 Zornitza Stark Gene: alg3 has been classified as Green List (High Evidence).
Arthrogryposis v0.73 ALG3 Zornitza Stark Classified gene: ALG3 as Green List (high evidence)
Arthrogryposis v0.73 ALG3 Zornitza Stark Gene: alg3 has been classified as Green List (High Evidence).
Arthrogryposis v0.72 ALG3 Zornitza Stark gene: ALG3 was added
gene: ALG3 was added to Arthrogryposis. Sources: Expert list
Mode of inheritance for gene: ALG3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALG3 were set to 16006436; 26453362; 28742265
Phenotypes for gene: ALG3 were set to Congenital disorder of glycosylation, type Id 601110
Review for gene: ALG3 was set to GREEN
Added comment: Multiple families reported with this CDG and contractures.
Sources: Expert list
Mendeliome v0.3291 C17orf62 Zornitza Stark Phenotypes for gene: C17orf62 were changed from Chronic granulomatous disease to Chronic granulomatous disease 5, autosomal recessive, MIM# 618935
Mendeliome v0.3290 C17orf62 Zornitza Stark Tag new gene name tag was added to gene: C17orf62.
Mendeliome v0.3290 C17orf62 Zornitza Stark edited their review of gene: C17orf62: Changed phenotypes: Chronic granulomatous disease 5, autosomal recessive, MIM# 618935
Phagocyte Defects v0.38 C17orf62 Zornitza Stark Phenotypes for gene: C17orf62 were changed from Chronic granulomatous disease to Chronic granulomatous disease 5, autosomal recessive, MIM# 618935
Phagocyte Defects v0.37 C17orf62 Zornitza Stark Tag new gene name tag was added to gene: C17orf62.
Phagocyte Defects v0.37 C17orf62 Zornitza Stark edited their review of gene: C17orf62: Changed phenotypes: Chronic granulomatous disease 5, autosomal recessive, MIM# 618935
Cataract v0.222 ITPA Zornitza Stark Marked gene: ITPA as ready
Cataract v0.222 ITPA Zornitza Stark Gene: itpa has been classified as Amber List (Moderate Evidence).
Cataract v0.222 ITPA Zornitza Stark Phenotypes for gene: ITPA were changed from to Epileptic encephalopathy, early infantile, 35, MIM# 616647
Cataract v0.221 ITPA Zornitza Stark Publications for gene: ITPA were set to
Cataract v0.220 ITPA Zornitza Stark Mode of inheritance for gene: ITPA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cataract v0.219 ITPA Zornitza Stark Classified gene: ITPA as Amber List (moderate evidence)
Cataract v0.219 ITPA Zornitza Stark Gene: itpa has been classified as Amber List (Moderate Evidence).
Cataract v0.218 ITPA Zornitza Stark reviewed gene: ITPA: Rating: AMBER; Mode of pathogenicity: None; Publications: 26224535, 30816001; Phenotypes: Epileptic encephalopathy, early infantile, 35, MIM# 616647; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.745 Zornitza Stark removed gene:NAXD from the panel
Leukodystrophy - paediatric v0.170 NAXD Zornitza Stark Marked gene: NAXD as ready
Leukodystrophy - paediatric v0.170 NAXD Zornitza Stark Gene: naxd has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.170 NAXD Zornitza Stark Classified gene: NAXD as Green List (high evidence)
Leukodystrophy - paediatric v0.170 NAXD Zornitza Stark Gene: naxd has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.169 NAXD Zornitza Stark gene: NAXD was added
gene: NAXD was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: NAXD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAXD were set to 32462209
Phenotypes for gene: NAXD were set to Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 2, 618321
Review for gene: NAXD was set to GREEN
Added comment: Variable phenotype: one patient reported with neurodevelopmental disorder, autism spectrum disorder and a muscular-dystrophy-like myopathy; another with progressive encephalopathy with brain oedema.
Sources: Expert list
Genetic Epilepsy v0.744 NAXD Elena Savva gene: NAXD was added
gene: NAXD was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: NAXD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAXD were set to PMID: 32462209
Phenotypes for gene: NAXD were set to Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 2, 618321
Review for gene: NAXD was set to GREEN
Added comment: Variable phenotype: one patient reported with neurodevelopmental disorder, autism spectrum disorder and a muscular-dystrophy-like myopathy

Patient reported with progressive encephalopathy with brain edema
Sources: Literature
Mendeliome v0.3290 DYSF Zornitza Stark Marked gene: DYSF as ready
Mendeliome v0.3290 DYSF Zornitza Stark Gene: dysf has been classified as Green List (High Evidence).
Mendeliome v0.3290 DYSF Zornitza Stark Phenotypes for gene: DYSF were changed from to Miyoshi muscular dystrophy 1 254130; Muscular dystrophy, limb-girdle, autosomal recessive 2 253601; Myopathy, distal, with anterior tibial onset 606768
Mendeliome v0.3289 DYSF Zornitza Stark Publications for gene: DYSF were set to
Mendeliome v0.3288 DYSF Zornitza Stark Mode of inheritance for gene: DYSF was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3287 NEB Zornitza Stark Marked gene: NEB as ready
Mendeliome v0.3287 NEB Zornitza Stark Gene: neb has been classified as Green List (High Evidence).
Mendeliome v0.3287 NEB Zornitza Stark Phenotypes for gene: NEB were changed from to Nemaline myopathy 2, autosomal recessive 256030
Mendeliome v0.3286 NEB Zornitza Stark Publications for gene: NEB were set to
Mendeliome v0.3285 NEB Zornitza Stark Mode of inheritance for gene: NEB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3284 MRPS34 Zornitza Stark reviewed gene: MRPS34: Rating: GREEN; Mode of pathogenicity: None; Publications: 28777931; Phenotypes: Combined oxidative phosphorylation deficiency 32, MIM# 617664; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3284 MRPS34 Zornitza Stark Marked gene: MRPS34 as ready
Mendeliome v0.3284 MRPS34 Zornitza Stark Gene: mrps34 has been classified as Green List (High Evidence).
Mendeliome v0.3284 MRPS34 Zornitza Stark Phenotypes for gene: MRPS34 were changed from to Combined oxidative phosphorylation deficiency 32, 61766
Mendeliome v0.3283 MRPS34 Zornitza Stark Publications for gene: MRPS34 were set to
Mendeliome v0.3282 MRPS34 Zornitza Stark Mode of inheritance for gene: MRPS34 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3281 MRPS34 Elena Savva reviewed gene: MRPS34: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28777931; Phenotypes: Combined oxidative phosphorylation deficiency 32, 61766; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3281 NEB Elena Savva reviewed gene: NEB: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 25205138; Phenotypes: Nemaline myopathy 2, autosomal recessive 256030; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3281 DYSF Elena Savva reviewed gene: DYSF: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 27602406; Phenotypes: Miyoshi muscular dystrophy 1 254130, Muscular dystrophy, limb-girdle, autosomal recessive 2 253601, Myopathy, distal, with anterior tibial onset 606768; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.29 HS6ST1 Bryony Thompson Marked gene: HS6ST1 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.29 HS6ST1 Bryony Thompson Gene: hs6st1 has been classified as Red List (Low Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.29 HS6ST1 Bryony Thompson Classified gene: HS6ST1 as Red List (low evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.29 HS6ST1 Bryony Thompson Gene: hs6st1 has been classified as Red List (Low Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.28 HARS2 Bryony Thompson Marked gene: HARS2 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.28 HARS2 Bryony Thompson Gene: hars2 has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.28 HARS2 Bryony Thompson Phenotypes for gene: HARS2 were changed from ?Perrault syndrome 2 614926 to Perrault syndrome 2 614926
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.27 HARS2 Bryony Thompson Publications for gene: HARS2 were set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.26 GNRHR Bryony Thompson Marked gene: GNRHR as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.26 GNRHR Bryony Thompson Gene: gnrhr has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.26 GNRHR Bryony Thompson Publications for gene: GNRHR were set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.25 GNRH1 Bryony Thompson Marked gene: GNRH1 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.25 GNRH1 Bryony Thompson Gene: gnrh1 has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.25 GNRH1 Bryony Thompson Phenotypes for gene: GNRH1 were changed from ?Hypogonadotropic hypogonadism 12 with or without anosmia 614841 to Hypogonadotropic hypogonadism 12 with or without anosmia 614841
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.24 GNRH1 Bryony Thompson Publications for gene: GNRH1 were set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.23 FLRT3 Bryony Thompson Marked gene: FLRT3 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.23 FLRT3 Bryony Thompson Gene: flrt3 has been classified as Red List (Low Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.23 FLRT3 Bryony Thompson Publications for gene: FLRT3 were set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.22 FLRT3 Bryony Thompson Classified gene: FLRT3 as Red List (low evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.22 FLRT3 Bryony Thompson Gene: flrt3 has been classified as Red List (Low Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.21 IL17RD Bryony Thompson Marked gene: IL17RD as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.21 IL17RD Bryony Thompson Gene: il17rd has been classified as Red List (Low Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.21 IL17RD Bryony Thompson Classified gene: IL17RD as Red List (low evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.21 IL17RD Bryony Thompson Gene: il17rd has been classified as Red List (Low Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.20 IL17RD Bryony Thompson Publications for gene: IL17RD were set to
Cataract v0.218 LCAT Zornitza Stark Classified gene: LCAT as Amber List (moderate evidence)
Cataract v0.218 LCAT Zornitza Stark Gene: lcat has been classified as Amber List (Moderate Evidence).
Cataract v0.217 LMX1B Zornitza Stark Classified gene: LMX1B as Amber List (moderate evidence)
Cataract v0.217 LMX1B Zornitza Stark Gene: lmx1b has been classified as Amber List (Moderate Evidence).
Cataract v0.216 LMX1B Zornitza Stark changed review comment from: Cataract is a feature of nail-patella syndrome.; to: Cataract is a reported feature of nail-patella syndrome but the typical finding is that of glaucoma.
Cataract v0.216 LMX1B Zornitza Stark edited their review of gene: LMX1B: Changed rating: AMBER
Cataract v0.216 LMX1B Zornitza Stark Marked gene: LMX1B as ready
Cataract v0.216 LMX1B Zornitza Stark Gene: lmx1b has been classified as Green List (High Evidence).
Cataract v0.216 LMX1B Zornitza Stark Phenotypes for gene: LMX1B were changed from to Nail-patella syndrome, MIM# 161200
Cataract v0.215 LMX1B Zornitza Stark Mode of inheritance for gene: LMX1B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cataract v0.214 LMX1B Zornitza Stark reviewed gene: LMX1B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Nail-patella syndrome, MIM# 161200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cataract v0.214 PIK3R1 Zornitza Stark Marked gene: PIK3R1 as ready
Cataract v0.214 PIK3R1 Zornitza Stark Gene: pik3r1 has been classified as Amber List (Moderate Evidence).
Cataract v0.214 PIK3R1 Zornitza Stark Phenotypes for gene: PIK3R1 were changed from to SHORT syndrome, MIM# 269880
Cataract v0.213 PIK3R1 Zornitza Stark Mode of inheritance for gene: PIK3R1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cataract v0.212 PIK3R1 Zornitza Stark Classified gene: PIK3R1 as Amber List (moderate evidence)
Cataract v0.212 PIK3R1 Zornitza Stark Gene: pik3r1 has been classified as Amber List (Moderate Evidence).
Cataract v0.211 PIK3R1 Zornitza Stark reviewed gene: PIK3R1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: SHORT syndrome, MIM# 269880; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cataract v0.211 GJA1 Zornitza Stark Marked gene: GJA1 as ready
Cataract v0.211 GJA1 Zornitza Stark Gene: gja1 has been classified as Red List (Low Evidence).
Cataract v0.211 GJA1 Zornitza Stark Phenotypes for gene: GJA1 were changed from to Oculodentodigital dysplasia, autosomal recessive, MIM# 257850
Cataract v0.210 GJA1 Zornitza Stark Mode of inheritance for gene: GJA1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cataract v0.209 GJA1 Zornitza Stark Classified gene: GJA1 as Red List (low evidence)
Cataract v0.209 GJA1 Zornitza Stark Gene: gja1 has been classified as Red List (Low Evidence).
Cataract v0.208 GJA1 Zornitza Stark reviewed gene: GJA1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Oculodentodigital dysplasia, autosomal recessive, MIM# 257850; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cataract v0.208 LCAT Zornitza Stark Marked gene: LCAT as ready
Cataract v0.208 LCAT Zornitza Stark Added comment: Comment when marking as ready: Some phenotypic overlap.
Cataract v0.208 LCAT Zornitza Stark Gene: lcat has been classified as Red List (Low Evidence).
Cataract v0.208 LCAT Zornitza Stark Classified gene: LCAT as Red List (low evidence)
Cataract v0.208 LCAT Zornitza Stark Gene: lcat has been classified as Red List (Low Evidence).
Cataract v0.207 ISPD Zornitza Stark reviewed gene: ISPD: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7 MIM#614643; Mode of inheritance: None
Differences of Sex Development v0.42 WNT4 Zornitza Stark Marked gene: WNT4 as ready
Differences of Sex Development v0.42 WNT4 Zornitza Stark Gene: wnt4 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.42 WNT4 Zornitza Stark Phenotypes for gene: WNT4 were changed from to Mullerian aplasia and hyperandrogenism (MIM#158330)
Differences of Sex Development v0.41 WNT4 Zornitza Stark Publications for gene: WNT4 were set to
Differences of Sex Development v0.40 WNT4 Zornitza Stark Mode of inheritance for gene: WNT4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.39 WNT4 Zornitza Stark Classified gene: WNT4 as Amber List (moderate evidence)
Differences of Sex Development v0.39 WNT4 Zornitza Stark Gene: wnt4 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.38 ZFPM2 Zornitza Stark reviewed gene: ZFPM2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Differences of Sex Development v0.38 ZFPM2 Zornitza Stark Marked gene: ZFPM2 as ready
Differences of Sex Development v0.38 ZFPM2 Zornitza Stark Gene: zfpm2 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.38 ZFPM2 Zornitza Stark Phenotypes for gene: ZFPM2 were changed from to 46XY sex reversal 9 (MIM#616067)
Differences of Sex Development v0.37 ZFPM2 Zornitza Stark Publications for gene: ZFPM2 were set to
Differences of Sex Development v0.36 ZFPM2 Zornitza Stark Mode of inheritance for gene: ZFPM2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.35 ZFPM2 Zornitza Stark Classified gene: ZFPM2 as Red List (low evidence)
Differences of Sex Development v0.35 ZFPM2 Zornitza Stark Gene: zfpm2 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.34 ZFPM2 Zornitza Stark Tag refuted tag was added to gene: ZFPM2.
Aortopathy_Connective Tissue Disorders v0.150 ATP6V1A Zornitza Stark Classified gene: ATP6V1A as Amber List (moderate evidence)
Aortopathy_Connective Tissue Disorders v0.150 ATP6V1A Zornitza Stark Gene: atp6v1a has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.149 ATP6V1A Zornitza Stark reviewed gene: ATP6V1A: Rating: AMBER; Mode of pathogenicity: None; Publications: 28065471; Phenotypes: Cutis laxa, autosomal recessive, type IID, MIM# 617403; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Aortopathy_Connective Tissue Disorders v0.149 PYCR1 Zornitza Stark Marked gene: PYCR1 as ready
Aortopathy_Connective Tissue Disorders v0.149 PYCR1 Zornitza Stark Gene: pycr1 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.149 PYCR1 Zornitza Stark Phenotypes for gene: PYCR1 were changed from to Cutis laxa, autosomal recessive, type IIB, MIM# 612940; Cutis laxa, autosomal recessive, type IIIB, MIM# 614438
Aortopathy_Connective Tissue Disorders v0.148 PYCR1 Zornitza Stark Classified gene: PYCR1 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.148 PYCR1 Zornitza Stark Gene: pycr1 has been classified as Green List (High Evidence).
Cataract v0.207 LCAT Dean Phelan gene: LCAT was added
gene: LCAT was added to Cataract. Sources: Literature
Mode of inheritance for gene: LCAT was set to BIALLELIC, autosomal or pseudoautosomal
Review for gene: LCAT was set to RED
Added comment: OMIM:
Norum disease (AR) - Corneal lipid deposits, Corneal opacities
Fish-eye disease (AR) - Corneal opacities

Discussion with ZS - Corneal opacities not the same as cataracts and often misdiagnosed. Therefore leave as Red at this stage.
Sources: Literature
Cataract v0.207 ISPD Seb Lunke Marked gene: ISPD as ready
Cataract v0.207 ISPD Seb Lunke Gene: ispd has been classified as Green List (High Evidence).
Cataract v0.207 ISPD Seb Lunke Classified gene: ISPD as Green List (high evidence)
Cataract v0.207 ISPD Seb Lunke Gene: ispd has been classified as Green List (High Evidence).
Cataract v0.206 ISPD Seb Lunke gene: ISPD was added
gene: ISPD was added to Cataract. Sources: Literature
Mode of inheritance for gene: ISPD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ISPD were set to 22522421; 22522420
Phenotypes for gene: ISPD were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7 MIM#614643
Added comment: >10 independent patients with congential cataract as part of muscular dystrophy presentation, plus functional studies in zebra fish.
Sources: Literature
Cataract v0.205 GFER Seb Lunke Marked gene: GFER as ready
Cataract v0.205 GFER Seb Lunke Gene: gfer has been classified as Green List (High Evidence).
Cataract v0.205 GFER Seb Lunke Publications for gene: GFER were set to 19409522; 25269795
Cataract v0.204 GFER Seb Lunke Classified gene: GFER as Green List (high evidence)
Cataract v0.204 GFER Seb Lunke Gene: gfer has been classified as Green List (High Evidence).
Cataract v0.203 GTF2H5 Zornitza Stark Marked gene: GTF2H5 as ready
Cataract v0.203 GTF2H5 Zornitza Stark Gene: gtf2h5 has been classified as Green List (High Evidence).
Cataract v0.203 GTF2H5 Zornitza Stark Classified gene: GTF2H5 as Green List (high evidence)
Cataract v0.203 GTF2H5 Zornitza Stark Gene: gtf2h5 has been classified as Green List (High Evidence).
Cataract v0.202 LONP1 Zornitza Stark Marked gene: LONP1 as ready
Cataract v0.202 LONP1 Zornitza Stark Gene: lonp1 has been classified as Green List (High Evidence).
Cataract v0.202 LONP1 Zornitza Stark Classified gene: LONP1 as Green List (high evidence)
Cataract v0.202 LONP1 Zornitza Stark Gene: lonp1 has been classified as Green List (High Evidence).
Cataract v0.201 GFER Paul De Fazio changed review comment from: Additional paper in 2017 brings the total count up to 8 cases from 4 unrelated families.; to: Additional paper in 2017 brings the total count up to 8 cases from 4 unrelated families (PMID: 28155230).
Cataract v0.201 GFER Paul De Fazio edited their review of gene: GFER: Added comment: Additional paper in 2017 brings the total count up to 8 cases from 4 unrelated families.; Changed rating: GREEN; Changed publications: 19409522, 25269795,28155230
Cataract v0.201 GTF2H5 Ain Roesley edited their review of gene: GTF2H5: Changed publications: 15220921, 24986372
Cataract v0.201 LONP1 Naomi Baker changed review comment from: Cataract is a common feature of CODAS (cerebral, ocular, dental, auricular, and skeletal anomalies) syndrome, which results from biallelic LONP1 mutations. One review of pateints with infantile cataract identified a biallelic LONP1 mutation in patient with stand-alone cataract (PMID: 29408517).
Sources: Literature; to: Cataract is a common feature of CODAS (cerebral, ocular, dental, auricular, and skeletal anomalies) syndrome, which results from biallelic LONP1 mutations. One review of patients with infantile cataract identified a biallelic LONP1 mutation in a patient who was otherwise healthy (PMID: 29408517).
Sources: Literature
Cataract v0.201 GTF2H5 Ain Roesley gene: GTF2H5 was added
gene: GTF2H5 was added to Cataract. Sources: Literature
Mode of inheritance for gene: GTF2H5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTF2H5 were set to 15220921,24986372
Phenotypes for gene: GTF2H5 were set to Trichothiodystrophy 3, photosensitive (MIM# 616395)
Penetrance for gene: GTF2H5 were set to unknown
Review for gene: GTF2H5 was set to GREEN
Added comment: PMID: 24986372;
A 5‐year‐old male, born as a collodion baby from healthy non‐consanguineous parents, exhibited sun sensitivity, brittle hair, ichthyosis, cataracts and mental/physical retardation. He demonstrated neither neurological abnormalities nor pigmentary changes following sun exposure. Homozygous for a nonsense variant.

PMID: 15220921;
2 out of 4 patients have cataracts. The 2 patients without cataracts are siblings. (2x homs for PTVs, 1x chet for PTV and missense)
Sources: Literature
Cataract v0.201 LONP1 Naomi Baker gene: LONP1 was added
gene: LONP1 was added to Cataract. Sources: Literature
Mode of inheritance for gene: LONP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LONP1 were set to PMID: 25574826; 29408517.
Phenotypes for gene: LONP1 were set to CODAS syndrome MIM# 600373
Penetrance for gene: LONP1 were set to Complete
Review for gene: LONP1 was set to GREEN
Added comment: Cataract is a common feature of CODAS (cerebral, ocular, dental, auricular, and skeletal anomalies) syndrome, which results from biallelic LONP1 mutations. One review of pateints with infantile cataract identified a biallelic LONP1 mutation in patient with stand-alone cataract (PMID: 29408517).
Sources: Literature
Cataract v0.201 GFER Paul De Fazio changed review comment from: One family (3 sibs born to healthy consang parents) described with progressive myopathy and partial combined respiratory-chain deficiency, congenital cataract, sensorineural hearing loss, and developmental delay had a homozygous missense variant (PMID:19409522).

Studies of patient fibroblasts and muscle tissue showed: a reduction in complex I, II, and IV activity; a lower cysteine-rich protein content; abnormal ultrastructural morphology of the mitochondria, with enlargement of the IMS space; and accelerated time-dependent accumulation of multiple mtDNA deletions. Additional functional studies in yeast also showed mitochondrial defects.
Sources: Literature; to: One family (3 sibs born to healthy consang parents) described with progressive myopathy and partial combined respiratory-chain deficiency, congenital cataract, sensorineural hearing loss, and developmental delay had a homozygous missense variant (PMID:19409522).

Studies of patient fibroblasts and muscle tissue showed: a reduction in complex I, II, and IV activity; a lower cysteine-rich protein content; abnormal ultrastructural morphology of the mitochondria, with enlargement of the IMS space; and accelerated time-dependent accumulation of multiple mtDNA deletions. Additional functional studies in yeast also showed mitochondrial defects.
Sources: Literature
Cataract v0.201 GEMIN4 Seb Lunke edited their review of gene: GEMIN4: Changed rating: AMBER; Changed phenotypes: Neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities, 617913
Cataract v0.201 GFER Paul De Fazio gene: GFER was added
gene: GFER was added to Cataract. Sources: Literature
Mode of inheritance for gene: GFER was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GFER were set to 19409522; 25269795
Phenotypes for gene: GFER were set to Myopathy, mitochondrial progressive, with congenital cataract, hearing loss, and developmental delay MIM#613076
Review for gene: GFER was set to AMBER
gene: GFER was marked as current diagnostic
Added comment: One family (3 sibs born to healthy consang parents) described with progressive myopathy and partial combined respiratory-chain deficiency, congenital cataract, sensorineural hearing loss, and developmental delay had a homozygous missense variant (PMID:19409522).

Studies of patient fibroblasts and muscle tissue showed: a reduction in complex I, II, and IV activity; a lower cysteine-rich protein content; abnormal ultrastructural morphology of the mitochondria, with enlargement of the IMS space; and accelerated time-dependent accumulation of multiple mtDNA deletions. Additional functional studies in yeast also showed mitochondrial defects.
Sources: Literature
Mendeliome v0.3281 GLS Zornitza Stark Phenotypes for gene: GLS were changed from Epileptic encephalopathy, early infantile, 71, MIM# 618328; Global developmental delay, progressive ataxia, and elevated glutamine, MIM# 618412 to Epileptic encephalopathy, early infantile, 71, MIM# 618328; Global developmental delay, progressive ataxia, and elevated glutamine, MIM# 618412; Cataract
Intellectual disability syndromic and non-syndromic v0.2747 GLS Zornitza Stark Mode of pathogenicity for gene: GLS was changed from None to Other
Mendeliome v0.3280 GLS Zornitza Stark Publications for gene: GLS were set to 30575854; 30970188
Mendeliome v0.3279 GLS Zornitza Stark Mode of inheritance for gene: GLS was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3278 GLS Zornitza Stark edited their review of gene: GLS: Added comment: In addition, single individual also reported with de novo, GoF variant with profound ID, cataract.; Changed publications: 30575854, 30970188, 30239721
Intellectual disability syndromic and non-syndromic v0.2746 GLS Zornitza Stark Publications for gene: GLS were set to 30970188
Mendeliome v0.3278 GLS Zornitza Stark edited their review of gene: GLS: Changed phenotypes: Epileptic encephalopathy, early infantile, 71, MIM# 618328, Global developmental delay, progressive ataxia, and elevated glutamine, MIM# 618412, Catarct; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2745 GLS Zornitza Stark Classified gene: GLS as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2745 GLS Zornitza Stark Gene: gls has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2744 GLS Zornitza Stark edited their review of gene: GLS: Added comment: Another three individuals from two unrelated families reported with early neonatal refractory seizures, structural brain abnormalities and oedema; significantly increased glutamine levels (PMID: 30575854).; Changed rating: GREEN; Changed publications: 30970188, 30239721, 30575854; Changed phenotypes: Epileptic encephalopathy, early infantile, 71, MIM# 618328, Global developmental delay, progressive ataxia, and elevated glutamine, MIM# 618412
Cataract v0.201 GLS Zornitza Stark Marked gene: GLS as ready
Cataract v0.201 GLS Zornitza Stark Gene: gls has been classified as Amber List (Moderate Evidence).
Cataract v0.201 GLS Zornitza Stark Classified gene: GLS as Amber List (moderate evidence)
Cataract v0.201 GLS Zornitza Stark Gene: gls has been classified as Amber List (Moderate Evidence).
Cataract v0.200 GLS Zornitza Stark gene: GLS was added
gene: GLS was added to Cataract. Sources: Expert list
Mode of inheritance for gene: GLS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GLS were set to 30239721
Phenotypes for gene: GLS were set to Infantile cataracts
Review for gene: GLS was set to AMBER
Added comment: Single family and a zebrafish model.
Sources: Expert list
Cataract v0.199 GEMIN4 Seb Lunke Marked gene: GEMIN4 as ready
Cataract v0.199 GEMIN4 Seb Lunke Gene: gemin4 has been classified as Amber List (Moderate Evidence).
Cataract v0.199 GEMIN4 Seb Lunke Classified gene: GEMIN4 as Amber List (moderate evidence)
Cataract v0.199 GEMIN4 Seb Lunke Gene: gemin4 has been classified as Amber List (Moderate Evidence).
Cataract v0.198 GEMIN4 Seb Lunke Marked gene: GEMIN4 as ready
Cataract v0.198 GEMIN4 Seb Lunke Added comment: Comment when marking as ready: 5 individuals from 3 consanguineous families reported originally; same homozygous missense in all. Another individual reported with different variant as part of a study reporting large number of novel/emerging genes in consanguineous cohort.
Cataract v0.198 GEMIN4 Seb Lunke Gene: gemin4 has been classified as Green List (High Evidence).
Cataract v0.198 GEMIN4 Seb Lunke Classified gene: GEMIN4 as Green List (high evidence)
Cataract v0.198 GEMIN4 Seb Lunke Gene: gemin4 has been classified as Green List (High Evidence).
Cataract v0.197 GEMIN4 Seb Lunke gene: GEMIN4 was added
gene: GEMIN4 was added to Cataract. Sources: Literature
Mode of inheritance for gene: GEMIN4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GEMIN4 were set to 25558065; 27878435
Phenotypes for gene: GEMIN4 were set to Neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities, 617913
Review for gene: GEMIN4 was set to GREEN
Added comment: From GEL: PMID: 25558065 reported on 5 affected patients from 3 unrelated consanguineous Saudi families with neurodevelopmental disorder, microcephaly cataracts and renal abnormalities. PMID: 27878435 reported on a different family with a different variant that was previously reported. The same paper also performed mouse studies and found that the gene is down regulated in key gene knockout mice with lens defects.
Sources: Literature
Cataract v0.196 NHS Zornitza Stark Marked gene: NHS as ready
Cataract v0.196 NHS Zornitza Stark Gene: nhs has been classified as Green List (High Evidence).
Cataract v0.196 NHS Zornitza Stark Phenotypes for gene: NHS were changed from to Nance-Horan syndrome (MIM# 302350)
Cataract v0.195 NHS Zornitza Stark Publications for gene: NHS were set to
Cataract v0.194 NHS Zornitza Stark Mode of inheritance for gene: NHS was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cataract v0.193 NF2 Zornitza Stark Marked gene: NF2 as ready
Cataract v0.193 NF2 Zornitza Stark Gene: nf2 has been classified as Green List (High Evidence).
Cataract v0.193 NF2 Zornitza Stark Phenotypes for gene: NF2 were changed from to Neurofibromatosis, type 2 (MIM# 101000)
Cataract v0.192 NF2 Zornitza Stark Mode of inheritance for gene: NF2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cataract v0.191 NDP Ain Roesley changed review comment from: Classified as "definitive" for Norrie Disease by ClinGen working group (https://search.clinicalgenome.org/kb/gene-validity/9611); to: Classified as "definitive" for Norrie Disease by ClinGen working group (https://search.clinicalgenome.org/kb/gene-validity/9611)

Progressive cataract is a feature of Norrie Disease (Genereviews, OMIM)
Cataract v0.191 NDP Zornitza Stark Marked gene: NDP as ready
Cataract v0.191 NDP Zornitza Stark Gene: ndp has been classified as Green List (High Evidence).
Cataract v0.191 NDP Zornitza Stark Phenotypes for gene: NDP were changed from to Norrie disease (MIM# 310600)
Cataract v0.190 NDP Zornitza Stark Mode of inheritance for gene: NDP was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cataract v0.189 FKTN Zornitza Stark Marked gene: FKTN as ready
Cataract v0.189 FKTN Zornitza Stark Gene: fktn has been classified as Amber List (Moderate Evidence).
Cataract v0.189 FKTN Zornitza Stark Phenotypes for gene: FKTN were changed from to Limb Girdle Muscular Dystrophy with No Mental Retardation; Congenital Cataract
Cataract v0.188 FKTN Zornitza Stark Publications for gene: FKTN were set to
Cataract v0.187 FKTN Zornitza Stark Mode of inheritance for gene: FKTN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cataract v0.186 FKTN Zornitza Stark Classified gene: FKTN as Amber List (moderate evidence)
Cataract v0.186 FKTN Zornitza Stark Gene: fktn has been classified as Amber List (Moderate Evidence).
Cataract v0.185 FBN1 Zornitza Stark Marked gene: FBN1 as ready
Cataract v0.185 FBN1 Zornitza Stark Gene: fbn1 has been classified as Green List (High Evidence).
Cataract v0.185 FBN1 Zornitza Stark Phenotypes for gene: FBN1 were changed from to Marfan syndrome, MIM# 154700; Weill-Marchesani syndrome 2, dominant, MIM# 608328
Cataract v0.184 FBN1 Zornitza Stark Mode of inheritance for gene: FBN1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cataract v0.183 ESCO2 Zornitza Stark Marked gene: ESCO2 as ready
Cataract v0.183 ESCO2 Zornitza Stark Added comment: Comment when marking as ready: Phenotypic overlap.
Cataract v0.183 ESCO2 Zornitza Stark Gene: esco2 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.147 PYCR1 Dean Phelan gene: PYCR1 was added
gene: PYCR1 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: PYCR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PYCR1 were set to PMID: 19648921; 4076251; 22052856; 19576563; 19648921; 9648921; 22052856; 28294978; 27756598
Review for gene: PYCR1 was set to GREEN
gene: PYCR1 was marked as current diagnostic
Added comment: Variants in this gene are associated with Cutis Laxa:
Cutis laxa type 2 (ARCL2, [MIM 219200]) is an autosomal-recessive multisystem disorder with prominent connective-tissue features characterized by the appearance of premature aging, particularly wrinkled and lax skin with reduced elasticity.

GEL PanelApp: Green in EDS panel - clinical features overlapping EDS
Cutis laxa, autosomal recessive, type IIIB (ARCL3B) PMID: 19648921,4076251, 22052856
Cutis laxa, autosomal recessive, type IIB (ARCL2B) PMID: 19576563, 19648921, 9648921, 22052856, 28294978 AR

PMID: 27756598: a homozygous mutation in PYCR1 segregating in the family with the affected individuals with complex connective tissue disorder and severe intellectual disability.
Sources: Literature
Cataract v0.183 ESCO2 Zornitza Stark Marked gene: ESCO2 as ready
Cataract v0.183 ESCO2 Zornitza Stark Gene: esco2 has been classified as Amber List (Moderate Evidence).
Cataract v0.183 ESCO2 Zornitza Stark Classified gene: ESCO2 as Amber List (moderate evidence)
Cataract v0.183 ESCO2 Zornitza Stark Gene: esco2 has been classified as Amber List (Moderate Evidence).
Cataract v0.182 NACC1 Zornitza Stark Marked gene: NACC1 as ready
Cataract v0.182 NACC1 Zornitza Stark Gene: nacc1 has been classified as Green List (High Evidence).
Cataract v0.182 NACC1 Zornitza Stark Phenotypes for gene: NACC1 were changed from to Neurodevelopmental disorder with epilepsy, cataracts, feeding difficulties, and delayed brain myelination delayed brain myelination (MIM# 617393)
Cataract v0.181 NACC1 Zornitza Stark Mode of inheritance for gene: NACC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3278 PYCR1 Dean Phelan changed review comment from: Aortopathy/Connective tissue review

Variants in this gene are associated with Cutis Laxa:
Cutis laxa type 2 (ARCL2, [MIM 219200]) is an autosomal-recessive multisystem disorder with prominent connective-tissue features characterized by the appearance of premature aging, particularly wrinkled and lax skin with reduced elasticity.

GEL PanelApp: Green in EDS panel - clinical features overlapping EDS
Cutis laxa, autosomal recessive, type IIIB (ARCL3B) PMID: 19648921,4076251, 22052856
Cutis laxa, autosomal recessive, type IIB (ARCL2B) PMID: 19576563, 19648921, 9648921, 22052856, 28294978 AR

PMID: 27756598: a homozygous mutation in PYCR1 segregating in the family with the affected individuals with complex connective tissue disorder and severe intellectual disability.; to: Aortopathy/Connective tissue review

Variants in this gene are associated with Cutis Laxa:
Cutis laxa type 2 (ARCL2, [MIM 219200]) is an autosomal-recessive multisystem disorder with prominent connective-tissue features characterized by the appearance of premature aging, particularly wrinkled and lax skin with reduced elasticity.

GEL PanelApp: Green in EDS panel - clinical features overlapping EDS
Cutis laxa, autosomal recessive, type IIIB (ARCL3B) PMID: 19648921,4076251, 22052856
Cutis laxa, autosomal recessive, type IIB (ARCL2B) PMID: 19576563, 19648921, 9648921, 22052856, 28294978 AR

PMID: 27756598: a homozygous mutation in PYCR1 segregating in the family with the affected individuals with complex connective tissue disorder and severe intellectual disability.
Mendeliome v0.3278 PYCR1 Seb Lunke Marked gene: PYCR1 as ready
Mendeliome v0.3278 PYCR1 Seb Lunke Gene: pycr1 has been classified as Green List (High Evidence).
Mendeliome v0.3278 PYCR1 Seb Lunke Phenotypes for gene: PYCR1 were changed from to cutis laxa
Mendeliome v0.3277 PYCR1 Seb Lunke Added comment: Comment on publications: 19648921; 4076251; 22052856; 19576563; 19648921; 9648921; 22052856; 28294978; 27756598
Mendeliome v0.3277 PYCR1 Seb Lunke Publications for gene: PYCR1 were set to
Differences of Sex Development v0.34 WNT4 Crystle Lee reviewed gene: WNT4: Rating: AMBER; Mode of pathogenicity: None; Publications: 22503279, 21377155, 16959810; Phenotypes: Mullerian aplasia and hyperandrogenism (MIM#158330); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.3276 PYCR1 Seb Lunke Mode of inheritance for gene: PYCR1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Aortopathy_Connective Tissue Disorders v0.147 PIEZO2 Zornitza Stark Marked gene: PIEZO2 as ready
Aortopathy_Connective Tissue Disorders v0.147 PIEZO2 Zornitza Stark Gene: piezo2 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.147 PIEZO2 Zornitza Stark Classified gene: PIEZO2 as Amber List (moderate evidence)
Aortopathy_Connective Tissue Disorders v0.147 PIEZO2 Zornitza Stark Gene: piezo2 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.146 RIN2 Zornitza Stark Marked gene: RIN2 as ready
Aortopathy_Connective Tissue Disorders v0.146 RIN2 Zornitza Stark Gene: rin2 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.146 RIN2 Zornitza Stark Classified gene: RIN2 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.146 RIN2 Zornitza Stark Gene: rin2 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.145 COL6A2 Seb Lunke Marked gene: COL6A2 as ready
Aortopathy_Connective Tissue Disorders v0.145 COL6A2 Seb Lunke Gene: col6a2 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.145 COL6A3 Zornitza Stark Marked gene: COL6A3 as ready
Aortopathy_Connective Tissue Disorders v0.145 COL6A3 Zornitza Stark Gene: col6a3 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.145 COL6A3 Zornitza Stark Classified gene: COL6A3 as Amber List (moderate evidence)
Aortopathy_Connective Tissue Disorders v0.145 COL6A3 Zornitza Stark Gene: col6a3 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.144 COL6A2 Seb Lunke Classified gene: COL6A2 as Amber List (moderate evidence)
Aortopathy_Connective Tissue Disorders v0.144 COL6A2 Seb Lunke Gene: col6a2 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.143 COL6A3 Zornitza Stark reviewed gene: COL6A3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Aortopathy_Connective Tissue Disorders v0.143 COL6A2 Seb Lunke reviewed gene: COL6A2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Aortopathy_Connective Tissue Disorders v0.143 LTBP4 Zornitza Stark Marked gene: LTBP4 as ready
Aortopathy_Connective Tissue Disorders v0.143 LTBP4 Zornitza Stark Gene: ltbp4 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.143 LTBP4 Zornitza Stark Classified gene: LTBP4 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.143 LTBP4 Zornitza Stark Gene: ltbp4 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.142 GORAB Zornitza Stark Marked gene: GORAB as ready
Aortopathy_Connective Tissue Disorders v0.142 GORAB Zornitza Stark Gene: gorab has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.142 GORAB Zornitza Stark Classified gene: GORAB as Amber List (moderate evidence)
Aortopathy_Connective Tissue Disorders v0.142 GORAB Zornitza Stark Gene: gorab has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.141 COL6A1 Zornitza Stark Marked gene: COL6A1 as ready
Aortopathy_Connective Tissue Disorders v0.141 COL6A1 Zornitza Stark Gene: col6a1 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.141 COL6A1 Zornitza Stark Classified gene: COL6A1 as Amber List (moderate evidence)
Aortopathy_Connective Tissue Disorders v0.141 COL6A1 Zornitza Stark Gene: col6a1 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.140 COL6A1 Zornitza Stark reviewed gene: COL6A1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Aortopathy_Connective Tissue Disorders v0.140 ATP6V1A Zornitza Stark Marked gene: ATP6V1A as ready
Aortopathy_Connective Tissue Disorders v0.140 ATP6V1A Zornitza Stark Gene: atp6v1a has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.140 ATP6V1A Zornitza Stark Classified gene: ATP6V1A as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.140 ATP6V1A Zornitza Stark Gene: atp6v1a has been classified as Green List (High Evidence).
Cataract v0.180 NHS Ain Roesley reviewed gene: NHS: Rating: GREEN; Mode of pathogenicity: None; Publications: 31755796; Phenotypes: Nance-Horan syndrome (MIM# 302350); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cataract v0.180 NF2 Ain Roesley reviewed gene: NF2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurofibromatosis, type 2 (MIM# 101000); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.34 ZFPM2 Crystle Lee reviewed gene: ZFPM2: Rating: AMBER; Mode of pathogenicity: None; Publications: 24549039, 27899157, 31962012, 12223418; Phenotypes: 46XY sex reversal 9 (MIM#616067); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Cataract v0.180 NDP Ain Roesley reviewed gene: NDP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Norrie disease (MIM# 310600); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cataract v0.180 FKTN Seb Lunke reviewed gene: FKTN: Rating: AMBER; Mode of pathogenicity: None; Publications: 18177472, 17878207; Phenotypes: Limb Girdle Muscular Dystrophy with No Mental Retardation, Congenital Cataract; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cataract v0.180 FKRP Seb Lunke reviewed gene: FKRP: Rating: AMBER; Mode of pathogenicity: None; Publications: 26833294; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cataract v0.180 FBN1 Seb Lunke reviewed gene: FBN1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cataract v0.180 ESCO2 Seb Lunke gene: ESCO2 was added
gene: ESCO2 was added to Cataract. Sources: Literature
Mode of inheritance for gene: ESCO2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ESCO2 were set to 19574259
Phenotypes for gene: ESCO2 were set to Craniofacial abnormalities; Developmental Delay; Corneal opacities; Growth retardation; Limb abnormalities; Roberts syndrome 238300
Review for gene: ESCO2 was set to AMBER
Added comment: Corneal opacities described in 13/36 cases with Roberts syndrome (RBS) and SC phocomelia are caused by mutations in ESCO2.
Sources: Literature
Hereditary Neuropathy_CMT - isolated v0.48 IGHMBP2 Zornitza Stark Marked gene: IGHMBP2 as ready
Hereditary Neuropathy_CMT - isolated v0.48 IGHMBP2 Zornitza Stark Gene: ighmbp2 has been classified as Green List (High Evidence).
Hereditary Neuropathy_CMT - isolated v0.48 IGHMBP2 Zornitza Stark Publications for gene: IGHMBP2 were set to
Intellectual disability syndromic and non-syndromic v0.2744 PLCB1 Zornitza Stark Marked gene: PLCB1 as ready
Intellectual disability syndromic and non-syndromic v0.2744 PLCB1 Zornitza Stark Gene: plcb1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2744 PLCB1 Zornitza Stark Phenotypes for gene: PLCB1 were changed from to Epileptic encephalopathy, early infantile, 12 (MIM#613722)
Intellectual disability syndromic and non-syndromic v0.2743 PLCB1 Zornitza Stark Publications for gene: PLCB1 were set to
Intellectual disability syndromic and non-syndromic v0.2742 PLCB1 Zornitza Stark Tag SV/CNV tag was added to gene: PLCB1.
Intellectual disability syndromic and non-syndromic v0.2742 PLCB1 Zornitza Stark Mode of inheritance for gene: PLCB1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.744 PLCB1 Zornitza Stark Marked gene: PLCB1 as ready
Genetic Epilepsy v0.744 PLCB1 Zornitza Stark Gene: plcb1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.744 PLCB1 Zornitza Stark Phenotypes for gene: PLCB1 were changed from to Epileptic encephalopathy, early infantile, 12 (MIM#613722)
Genetic Epilepsy v0.743 PLCB1 Zornitza Stark Publications for gene: PLCB1 were set to
Genetic Epilepsy v0.742 PLCB1 Zornitza Stark Mode of inheritance for gene: PLCB1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.741 PLCB1 Zornitza Stark Tag SV/CNV tag was added to gene: PLCB1.
Intellectual disability syndromic and non-syndromic v0.2741 PIGY Zornitza Stark Marked gene: PIGY as ready
Intellectual disability syndromic and non-syndromic v0.2741 PIGY Zornitza Stark Gene: pigy has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2741 PIGY Zornitza Stark Phenotypes for gene: PIGY were changed from to Hyperphosphatasia with mental retardation syndrome 6, MIM# 616809
Intellectual disability syndromic and non-syndromic v0.2740 PIGY Zornitza Stark Publications for gene: PIGY were set to
Intellectual disability syndromic and non-syndromic v0.2739 PIGY Zornitza Stark Mode of inheritance for gene: PIGY was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2738 PIGY Zornitza Stark Classified gene: PIGY as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2738 PIGY Zornitza Stark Gene: pigy has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3275 PIGY Zornitza Stark Marked gene: PIGY as ready
Mendeliome v0.3275 PIGY Zornitza Stark Gene: pigy has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3275 PIGY Zornitza Stark Phenotypes for gene: PIGY were changed from to Hyperphosphatasia with mental retardation syndrome 6, MIM# 616809
Mendeliome v0.3274 PIGY Zornitza Stark Publications for gene: PIGY were set to
Mendeliome v0.3273 PIGY Zornitza Stark Mode of inheritance for gene: PIGY was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3272 PIGY Zornitza Stark Classified gene: PIGY as Amber List (moderate evidence)
Mendeliome v0.3272 PIGY Zornitza Stark Gene: pigy has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v0.55 MYBPC3 Zornitza Stark Marked gene: MYBPC3 as ready
Muscular dystrophy and myopathy_Paediatric v0.55 MYBPC3 Zornitza Stark Gene: mybpc3 has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v0.55 MYBPC3 Zornitza Stark Classified gene: MYBPC3 as Red List (low evidence)
Muscular dystrophy and myopathy_Paediatric v0.55 MYBPC3 Zornitza Stark Gene: mybpc3 has been classified as Red List (Low Evidence).
Cataract v0.179 NACC1 Ain Roesley reviewed gene: NACC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28132692; Phenotypes: Neurodevelopmental disorder with epilepsy, cataracts, feeding difficulties, and delayed brain myelination delayed brain myelination (MIM# 617393); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3271 MTMR14 Zornitza Stark Marked gene: MTMR14 as ready
Mendeliome v0.3271 MTMR14 Zornitza Stark Added comment: Comment when marking as ready: Single family and animal models; postulated to be a modifier in the other family.
Mendeliome v0.3271 MTMR14 Zornitza Stark Gene: mtmr14 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3271 MTMR14 Zornitza Stark Classified gene: MTMR14 as Amber List (moderate evidence)
Mendeliome v0.3271 MTMR14 Zornitza Stark Gene: mtmr14 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3270 MTMR14 Zornitza Stark Deleted their comment
Mendeliome v0.3270 MTMR14 Zornitza Stark Marked gene: MTMR14 as ready
Mendeliome v0.3270 MTMR14 Zornitza Stark Added comment: Comment when marking as ready: Postulated to be a modifier.
Mendeliome v0.3270 MTMR14 Zornitza Stark Gene: mtmr14 has been classified as Red List (Low Evidence).
Mendeliome v0.3270 MTMR14 Zornitza Stark Publications for gene: MTMR14 were set to
Mendeliome v0.3269 MTMR14 Zornitza Stark Mode of inheritance for gene: MTMR14 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cataract v0.179 EIF2B2 Zornitza Stark Phenotypes for gene: EIF2B2 were changed from leukodystrophy; congenital cataracts to leukodystrophy; congenital cataracts; Leukoencephalopathy with vanishing white matter, MIM# 603896
Cataract v0.178 EIF2B2 Zornitza Stark reviewed gene: EIF2B2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Leukoencephalopathy with vanishing white matter, MIM# 603896; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy_CMT - isolated v0.47 IGHMBP2 Crystle Lee changed review comment from: >5 families reported with CMT2.; to: >5 families reported with CMT2. Complete loss of protein function appears to result in the move severe condition (spinal muscular atrophy with respiratory distress type 1 (SMARD1) [MIM#604320])
Hereditary Neuropathy_CMT - isolated v0.47 IGHMBP2 Crystle Lee reviewed gene: IGHMBP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25439726; Phenotypes: Charcot-Marie-Tooth disease, axonal, type 2S (MIM#616155); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3268 P4HA1 Zornitza Stark Marked gene: P4HA1 as ready
Mendeliome v0.3268 P4HA1 Zornitza Stark Gene: p4ha1 has been classified as Red List (Low Evidence).
Mendeliome v0.3268 P4HA1 Zornitza Stark gene: P4HA1 was added
gene: P4HA1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: P4HA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: P4HA1 were set to 28419360
Phenotypes for gene: P4HA1 were set to Joint hypermobility; Contractures; Hypotonia; Mild skeletal dysplasia without bone fragility; High myopia
Review for gene: P4HA1 was set to RED
Added comment: Single family reported with two affected individuals.
Sources: Expert list
Aortopathy_Connective Tissue Disorders v0.139 P4HA1 Zornitza Stark Marked gene: P4HA1 as ready
Aortopathy_Connective Tissue Disorders v0.139 P4HA1 Zornitza Stark Gene: p4ha1 has been classified as Red List (Low Evidence).
Aortopathy_Connective Tissue Disorders v0.139 P4HA1 Zornitza Stark gene: P4HA1 was added
gene: P4HA1 was added to Aortopathy_Connective Tissue Disorders. Sources: Expert list
Mode of inheritance for gene: P4HA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: P4HA1 were set to 28419360
Phenotypes for gene: P4HA1 were set to Joint hypermobility; Contractures; Hypotonia; Mild skeletal dysplasia without bone fragility; High myopia
Review for gene: P4HA1 was set to RED
Added comment: Single family reported with two affected individuals.
Sources: Expert list
Aortopathy_Connective Tissue Disorders v0.138 GORAB Paul De Fazio changed review comment from: 13 families described with biallelic LoF variants (PMID: 18997784). Phenotypes included wrinkly skin and osteoporosis.

One more individual described with a homozygous missense variant (PMID: 19681135). Clinical diagnosis of GO was based on the presence of typical facial features, reduced skin elasticity, and decreased bone density.

There have been no clinical reports since 2009.

This gene is Green in PanelApp England because it has phenotypic overlap with Eherls Danlos syndrome. I have left it amber as I'm not sure if the overlap is sufficient for this panel.

From OMIM: "Geroderma osteodysplasticum (GO) is an autosomal recessive disorder characterized by skin wrinkling limited to the dorsa of hands and feet and to the abdomen, bowed long bones, and osteopenia with frequent fractures. There is a distinctive facial appearance with droopy skin at the cheeks, maxillary hypoplasia, and large ears. Adult patients appear prematurely aged"
Sources: Literature; to: 13 families described with biallelic LoF variants (PMID: 18997784). Phenotypes included wrinkly skin and osteoporosis.

One more individual described with a homozygous missense variant (PMID: 19681135). Clinical diagnosis of GO was based on the presence of typical facial features, reduced skin elasticity, and decreased bone density.

There have been no clinical reports since 2009.

This gene is Green in PanelApp England EDS panel because it has phenotypic overlap with Eherls Danlos syndrome. I have left it amber as I'm not sure if the overlap is sufficient for this panel.

From OMIM: "Geroderma osteodysplasticum (GO) is an autosomal recessive disorder characterized by skin wrinkling limited to the dorsa of hands and feet and to the abdomen, bowed long bones, and osteopenia with frequent fractures. There is a distinctive facial appearance with droopy skin at the cheeks, maxillary hypoplasia, and large ears. Adult patients appear prematurely aged"
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.138 GORAB Paul De Fazio changed review comment from: 13 families described with biallelic LoF variants (PMID: 18997784). Phenotypes included wrinkly skin and osteoporosis.

One more individual described with a homozygous missense variant (PMID: 19681135). Clinical diagnosis of GO was based on the presence of typical facial features, reduced skin elasticity, and decreased bone density.

There have been no clinical reports since 2009.

This gene is Green in PanelApp England because it has phenotypic overlap with Eherls Danlos syndrome.

From OMIM: "Geroderma osteodysplasticum (GO) is an autosomal recessive disorder characterized by skin wrinkling limited to the dorsa of hands and feet and to the abdomen, bowed long bones, and osteopenia with frequent fractures. There is a distinctive facial appearance with droopy skin at the cheeks, maxillary hypoplasia, and large ears. Adult patients appear prematurely aged"
Sources: Literature; to: 13 families described with biallelic LoF variants (PMID: 18997784). Phenotypes included wrinkly skin and osteoporosis.

One more individual described with a homozygous missense variant (PMID: 19681135). Clinical diagnosis of GO was based on the presence of typical facial features, reduced skin elasticity, and decreased bone density.

There have been no clinical reports since 2009.

This gene is Green in PanelApp England because it has phenotypic overlap with Eherls Danlos syndrome. I have left it amber as I'm not sure if the overlap is sufficient for this panel.

From OMIM: "Geroderma osteodysplasticum (GO) is an autosomal recessive disorder characterized by skin wrinkling limited to the dorsa of hands and feet and to the abdomen, bowed long bones, and osteopenia with frequent fractures. There is a distinctive facial appearance with droopy skin at the cheeks, maxillary hypoplasia, and large ears. Adult patients appear prematurely aged"
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.138 GORAB Paul De Fazio changed review comment from: 13 families described with biallelic LoF variants (PMID: 18997784). Phenotypes included wrinkly skin and osteoporosis.

One more individual described with a homozygous missense variant (PMID: 19681135). Clinical diagnosis of GO was based on the presence of typical facial features, reduced skin elasticity, and decreased bone density.

There have been no clinical reports since 2009.

This gene is Green in PanelApp England because it has phenotypic overlap with Eherls Danlos syndrome.
Sources: Literature; to: 13 families described with biallelic LoF variants (PMID: 18997784). Phenotypes included wrinkly skin and osteoporosis.

One more individual described with a homozygous missense variant (PMID: 19681135). Clinical diagnosis of GO was based on the presence of typical facial features, reduced skin elasticity, and decreased bone density.

There have been no clinical reports since 2009.

This gene is Green in PanelApp England because it has phenotypic overlap with Eherls Danlos syndrome.

From OMIM: "Geroderma osteodysplasticum (GO) is an autosomal recessive disorder characterized by skin wrinkling limited to the dorsa of hands and feet and to the abdomen, bowed long bones, and osteopenia with frequent fractures. There is a distinctive facial appearance with droopy skin at the cheeks, maxillary hypoplasia, and large ears. Adult patients appear prematurely aged"
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.138 PIEZO2 Paul De Fazio changed review comment from: 1 individual diagnosed with Marden-Walker syndrome was described with a de novo missense variant in this gene (PMID: 24726473). This is the only literature supporting this gene-disease association. One other proband with MWS did not have a variant in this gene.

The same study reported that another 10 families/individuals with Gordon syndrome (distal arthrogryposis type 3) and 24 with distal atrogryposis type 5 had variants in this gene. The authors posit that these three conditions represent a spectrum of disease.

Marden-Walker syndrome is described as a connective tissue disorder (https://rarediseases.info.nih.gov/diseases/6973/marden-walker-syndrome) and has significant overlap with other multi-system congenital contracture syndromes including D4ST1-Deficient Ehlers-Danlos syndrome (adducted thumb-clubfoot syndrome) (PMID: 27375131). GEL has this gene as Amber in the EDS panel noting some overlap with Kyphoscoliotic EDS in terms of scoliosis.
Sources: Literature; to: 1 individual diagnosed with Marden-Walker syndrome was described with a de novo missense variant in this gene (PMID: 24726473). This is the only literature supporting this gene-disease association. One other proband with MWS did not have a variant in this gene although the authors note that their sequencing strategy would not have been able to detect some indels including single-exon deletions.

The same study reported that another 10 families/individuals with Gordon syndrome (distal arthrogryposis type 3) and 24 with distal atrogryposis type 5 had variants in this gene. The authors posit that these three conditions represent a spectrum of disease.

Marden-Walker syndrome is described as a connective tissue disorder (https://rarediseases.info.nih.gov/diseases/6973/marden-walker-syndrome) and has significant overlap with other multi-system congenital contracture syndromes including D4ST1-Deficient Ehlers-Danlos syndrome (adducted thumb-clubfoot syndrome) (PMID: 27375131). GEL has this gene as Amber in the EDS panel noting some overlap with Kyphoscoliotic EDS in terms of scoliosis.
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.138 PIEZO2 Paul De Fazio changed review comment from: 1 individual diagnosed with Marden-Walker syndrome was described with a de novo missense variant in this gene (PMID: 24726473). Another 10 families/individuals with Gordon syndrome (distal arthrogryposis type 3) and 24 with distal atrogryposis type 5 had variants in this gene. The authors posit that these three conditions represent a spectrum of disease.

Marden-Walker syndrome is described as a connective tissue disorder (https://rarediseases.info.nih.gov/diseases/6973/marden-walker-syndrome) and has significant overlap with other multi-system congenital contracture syndromes including D4ST1-Deficient Ehlers-Danlos syndrome (adducted thumb-clubfoot syndrome) (PMID: 27375131). GEL has this gene as Amber in the EDS panel noting some overlap with Kyphoscoliotic EDS in terms of scoliosis.
Sources: Literature; to: 1 individual diagnosed with Marden-Walker syndrome was described with a de novo missense variant in this gene (PMID: 24726473). This is the only literature supporting this gene-disease association. One other proband with MWS did not have a variant in this gene.

The same study reported that another 10 families/individuals with Gordon syndrome (distal arthrogryposis type 3) and 24 with distal atrogryposis type 5 had variants in this gene. The authors posit that these three conditions represent a spectrum of disease.

Marden-Walker syndrome is described as a connective tissue disorder (https://rarediseases.info.nih.gov/diseases/6973/marden-walker-syndrome) and has significant overlap with other multi-system congenital contracture syndromes including D4ST1-Deficient Ehlers-Danlos syndrome (adducted thumb-clubfoot syndrome) (PMID: 27375131). GEL has this gene as Amber in the EDS panel noting some overlap with Kyphoscoliotic EDS in terms of scoliosis.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2737 PLCB1 Crystle Lee reviewed gene: PLCB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24684524, 20833646, 22690784, 26818157; Phenotypes: Epileptic encephalopathy, early infantile, 12 (MIM#613722); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Aortopathy_Connective Tissue Disorders v0.138 PIEZO2 Paul De Fazio edited their review of gene: PIEZO2: Changed publications: 24726473, 27375131
Aortopathy_Connective Tissue Disorders v0.138 PIEZO2 Paul De Fazio changed review comment from: 1 individual diagnosed with Marden-Walker syndrome was described with a de novo missense variant in this gene (PMID: 24726473). Another 10 families/individuals with Gordon syndrome (distal arthrogryposis type 3) and 24 with distal atrogryposis type 5 had variants in this gene. The authors posit that these three conditions represent a spectrum of disease.

Marden-Walker syndrome is described as a connective tissue disorder (https://rarediseases.info.nih.gov/diseases/6973/marden-walker-syndrome) and has significant overlap with other multi-system congenital contracture syndromes including D4ST1-Deficient Ehlers-Danlos syndrome (adducted thumb-clubfoot syndrome). GEL has this gene as Amber in the EDS panel noting some overlap with Kyphoscoliotic EDS in terms of scoliosis.
Sources: Literature; to: 1 individual diagnosed with Marden-Walker syndrome was described with a de novo missense variant in this gene (PMID: 24726473). Another 10 families/individuals with Gordon syndrome (distal arthrogryposis type 3) and 24 with distal atrogryposis type 5 had variants in this gene. The authors posit that these three conditions represent a spectrum of disease.

Marden-Walker syndrome is described as a connective tissue disorder (https://rarediseases.info.nih.gov/diseases/6973/marden-walker-syndrome) and has significant overlap with other multi-system congenital contracture syndromes including D4ST1-Deficient Ehlers-Danlos syndrome (adducted thumb-clubfoot syndrome) (PMID: 27375131). GEL has this gene as Amber in the EDS panel noting some overlap with Kyphoscoliotic EDS in terms of scoliosis.
Sources: Literature
Genetic Epilepsy v0.741 PLCB1 Crystle Lee reviewed gene: PLCB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24684524, 20833646, 22690784, 26818157; Phenotypes: Epileptic encephalopathy, early infantile, 12 (MIM#613722); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Aortopathy_Connective Tissue Disorders v0.138 PIEZO2 Paul De Fazio gene: PIEZO2 was added
gene: PIEZO2 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: PIEZO2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIEZO2 were set to 24726473
Phenotypes for gene: PIEZO2 were set to Marden-Walker syndrome (MIM#248700); Arthrogryposis, distal, type 3 (MIM#114300); Arthrogryposis, distal, type 5 (MIM#108145)
Review for gene: PIEZO2 was set to AMBER
gene: PIEZO2 was marked as current diagnostic
Added comment: 1 individual diagnosed with Marden-Walker syndrome was described with a de novo missense variant in this gene (PMID: 24726473). Another 10 families/individuals with Gordon syndrome (distal arthrogryposis type 3) and 24 with distal atrogryposis type 5 had variants in this gene. The authors posit that these three conditions represent a spectrum of disease.

Marden-Walker syndrome is described as a connective tissue disorder (https://rarediseases.info.nih.gov/diseases/6973/marden-walker-syndrome) and has significant overlap with other multi-system congenital contracture syndromes including D4ST1-Deficient Ehlers-Danlos syndrome (adducted thumb-clubfoot syndrome). GEL has this gene as Amber in the EDS panel noting some overlap with Kyphoscoliotic EDS in terms of scoliosis.
Sources: Literature
Mendeliome v0.3267 ROBO3 Ain Roesley reviewed gene: ROBO3: Rating: GREEN; Mode of pathogenicity: None; Publications: 15105459, 32373565; Phenotypes: Gaze palsy, familial horizontal, with progressive scoliosis, 1 (MIM# 607313); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3267 PIGY Elena Savva reviewed gene: PIGY: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 26293662; Phenotypes: Hyperphosphatasia with mental retardation syndrome 6, MIM# 616809; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.54 MYBPC3 Elena Savva gene: MYBPC3 was added
gene: MYBPC3 was added to Muscular dystrophy. Sources: Expert list
Mode of inheritance for gene: MYBPC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYBPC3 were set to PMID: 19858127
Phenotypes for gene: MYBPC3 were set to Cardiomyopathy with myopathy
Review for gene: MYBPC3 was set to RED
Added comment: Single report of a dystrophy, patient was homozygous for a PTC.
Sources: Expert list
Mendeliome v0.3267 PYCR1 Dean Phelan reviewed gene: PYCR1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 19648921, 4076251, 22052856, 19576563, 19648921, 9648921, 22052856, 28294978, 27756598; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.362 GGPS1 Zornitza Stark Marked gene: GGPS1 as ready
Deafness_IsolatedAndComplex v0.362 GGPS1 Zornitza Stark Gene: ggps1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.362 GGPS1 Zornitza Stark Classified gene: GGPS1 as Green List (high evidence)
Deafness_IsolatedAndComplex v0.362 GGPS1 Zornitza Stark Gene: ggps1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.361 GGPS1 Zornitza Stark gene: GGPS1 was added
gene: GGPS1 was added to Deafness. Sources: Literature
Mode of inheritance for gene: GGPS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GGPS1 were set to 32403198
Phenotypes for gene: GGPS1 were set to Muscular dystrophy; Deafness; Ovarian insufficiency
Review for gene: GGPS1 was set to GREEN
Added comment: 11 individuals from 6 unrelated families reported. In addition to proximal weakness, all but one patient presented with congenital sensorineural hearing loss, and all postpubertal females had primary ovarian insufficiency. Muscle histology was dystrophic, with ultrastructural evidence of autophagic material and large mitochondria in the most severe cases. Knock-in mouse of one of the mutations (Y259C) resulted in prenatal lethality.
Sources: Literature
Mendeliome v0.3267 GGPS1 Zornitza Stark Marked gene: GGPS1 as ready
Mendeliome v0.3267 GGPS1 Zornitza Stark Gene: ggps1 has been classified as Green List (High Evidence).
Mendeliome v0.3267 GGPS1 Zornitza Stark Classified gene: GGPS1 as Green List (high evidence)
Mendeliome v0.3267 GGPS1 Zornitza Stark Gene: ggps1 has been classified as Green List (High Evidence).
Mendeliome v0.3266 GGPS1 Zornitza Stark gene: GGPS1 was added
gene: GGPS1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GGPS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GGPS1 were set to 32403198
Phenotypes for gene: GGPS1 were set to Muscular dystrophy; Deafness; Ovarian insufficiency
Review for gene: GGPS1 was set to GREEN
Added comment: 11 individuals from 6 unrelated families reported. In addition to proximal weakness, all but one patient presented with congenital sensorineural hearing loss, and all postpubertal females had primary ovarian insufficiency. Muscle histology was dystrophic, with ultrastructural evidence of autophagic material and large mitochondria in the most severe cases. Knock-in mouse of one of the mutations (Y259C) resulted in prenatal lethality.
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v0.54 GGPS1 Zornitza Stark Marked gene: GGPS1 as ready
Muscular dystrophy and myopathy_Paediatric v0.54 GGPS1 Zornitza Stark Gene: ggps1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.54 GGPS1 Zornitza Stark Classified gene: GGPS1 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.54 GGPS1 Zornitza Stark Gene: ggps1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.53 GGPS1 Zornitza Stark gene: GGPS1 was added
gene: GGPS1 was added to Muscular dystrophy. Sources: Literature
Mode of inheritance for gene: GGPS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GGPS1 were set to 32403198
Phenotypes for gene: GGPS1 were set to Muscular dystrophy; Deafness; Ovarian insufficiency
Review for gene: GGPS1 was set to GREEN
Added comment: 11 individuals from 6 unrelated families reported. In addition to proximal weakness, all but one patient presented with congenital sensorineural hearing loss, and all postpubertal females had primary ovarian insufficiency. Muscle histology was dystrophic, with ultrastructural evidence of autophagic material and large mitochondria in the most severe cases. Knock-in mouse of one of the mutations (Y259C) resulted in prenatal lethality.
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.138 RIN2 Ain Roesley gene: RIN2 was added
gene: RIN2 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: RIN2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RIN2 were set to 19631308; 20424861; 23963297; 24449201
Phenotypes for gene: RIN2 were set to Macrocephaly, alopecia, cutis laxa, and scoliosis (MIM# 613075)
Penetrance for gene: RIN2 were set to unknown
Review for gene: RIN2 was set to GREEN
Added comment: Also known as MACS syndrome. The most striking clinical features include macrocephaly, progressive facial coarsening, gingival hypertrophy, severe scoliosis, sparse hair and skin and joint hyperlaxity. All families reported thus far are homozygous for PTVs

PMID: 19631308; 1x large consanguineous kindred with 3 affecteds

PMID: 20424861; 1x consanguineous Algerian family with three affected siblings.

PMID: 23963297; 1x patient with MACS syndrome and an additional phenotype of periventricular cystic lesions

PMID: 24449201; 2 sibs born to non-consanguineous Turkish parents exhibiting additional clinical features of bronchiectasis and hypergonadotropic hypogonadism.
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.138 LTBP4 Ain Roesley edited their review of gene: LTBP4: Changed publications: 22829427; Changed phenotypes: Cutis laxa, autosomal recessive, type IC (MIM# 613177)
Aortopathy_Connective Tissue Disorders v0.138 ATP6V1A Ain Roesley edited their review of gene: ATP6V1A: Changed publications: 28065471
Aortopathy_Connective Tissue Disorders v0.138 COL6A3 Naomi Baker gene: COL6A3 was added
gene: COL6A3 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: COL6A3 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: COL6A3 were set to PMID: 29277723; 24443028.
Phenotypes for gene: COL6A3 were set to Bethlem myopathy 1 MIM #158810; Ullrich congenital muscular dystrophy 1 MIM #254090
Penetrance for gene: COL6A3 were set to Complete
Mode of pathogenicity for gene: COL6A3 was set to Other
Review for gene: COL6A3 was set to GREEN
Added comment: Both loss-of-function and dominant negative mechanism has been reported for this gene. Mutations result in a spectrum of disease, ranging from the milder Bethlem myopathy (monoallelic) to the more severe Ullrich congenital muscular dystrophy (biallelic) (PMID: 29277723; 24443028).
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.138 COL6A2 Naomi Baker gene: COL6A2 was added
gene: COL6A2 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: COL6A2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: COL6A2 were set to (PMID: 29277723; 24443028)
Phenotypes for gene: COL6A2 were set to Bethlem myopathy 1 MIM #158810; Ullrich congenital muscular dystrophy 1 MIM #254090
Penetrance for gene: COL6A2 were set to Complete
Mode of pathogenicity for gene: COL6A2 was set to Other
Review for gene: COL6A2 was set to GREEN
Added comment: Both loss-of-function and dominant negative mechanism has been reported for this gene. Mutations result in a spectrum of disease, ranging from the milder Bethlem myopathy (monoallelic) to the more severe Ullrich congenital muscular dystrophy (biallelic) (PMID: 29277723; 24443028).
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.138 LTBP4 Ain Roesley gene: LTBP4 was added
gene: LTBP4 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: LTBP4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LTBP4 were set to PMID: 22829427
Phenotypes for gene: LTBP4 were set to Cutis laxa, autosomal recessive, type IC (MIM# 613177)
Penetrance for gene: LTBP4 were set to unknown
Review for gene: LTBP4 was set to GREEN
Added comment: PMID: 22829427;
- 9 families with cutis laxa, either homozygotes or cHets.
- all PTVs except 1 homozygous missense
- Most LTBP4 mutation positive patients (11/13) had generalized moderate to severe cutis laxa, skin was hyperextensible, or appeared translucent with a prominent venous pattern (3/9), few patients had thin and slowly growing hair and inguinal and diaphragmatic hernias (5/9)
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.138 GORAB Paul De Fazio gene: GORAB was added
gene: GORAB was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: GORAB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GORAB were set to 18997784; 19681135
Phenotypes for gene: GORAB were set to Geroderma osteodysplasticum MIM#231070
Review for gene: GORAB was set to AMBER
gene: GORAB was marked as current diagnostic
Added comment: 13 families described with biallelic LoF variants (PMID: 18997784). Phenotypes included wrinkly skin and osteoporosis.

One more individual described with a homozygous missense variant (PMID: 19681135). Clinical diagnosis of GO was based on the presence of typical facial features, reduced skin elasticity, and decreased bone density.

There have been no clinical reports since 2009.

This gene is Green in PanelApp England because it has phenotypic overlap with Eherls Danlos syndrome.
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.138 COL6A1 Naomi Baker gene: COL6A1 was added
gene: COL6A1 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: COL6A1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: COL6A1 were set to PMID: 29277723; 24443028.
Phenotypes for gene: COL6A1 were set to Bethlem myopathy 1 MIM #158810; Ullrich congenital muscular dystrophy 1 MIM #254090
Penetrance for gene: COL6A1 were set to Complete
Mode of pathogenicity for gene: COL6A1 was set to Other
Review for gene: COL6A1 was set to GREEN
Added comment: Both loss-of-function and dominant negative mechanism has been reported for this gene. Mutations result in a spectrum of disease, ranging from the milder Bethlem myopathy (monoallelic) to the more severe Ullrich congenital muscular dystrophy (biallelic) (PMID: 29277723; 24443028).
Sources: Literature
Cataract v0.178 EIF2B2 Seb Lunke Marked gene: EIF2B2 as ready
Cataract v0.178 EIF2B2 Seb Lunke Gene: eif2b2 has been classified as Green List (High Evidence).
Cataract v0.178 EIF2B2 Seb Lunke Classified gene: EIF2B2 as Green List (high evidence)
Cataract v0.178 EIF2B2 Seb Lunke Gene: eif2b2 has been classified as Green List (High Evidence).
Mendeliome v0.3265 MTMR14 Elena Savva reviewed gene: MTMR14: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 20400459, 20817957, 19465920, 17008356; Phenotypes: {Centronuclear myopathy, autosomal, modifier of}, MIM# 160150; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Cataract v0.177 EIF2B2 Seb Lunke gene: EIF2B2 was added
gene: EIF2B2 was added to Cataract. Sources: Literature
Mode of inheritance for gene: EIF2B2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EIF2B2 were set to 21484434; 14566705; 28041799
Phenotypes for gene: EIF2B2 were set to leukodystrophy; congenital cataracts
gene: EIF2B2 was marked as current diagnostic
Added comment: From GEL: There are 3 unrelated cases (PMID: 21484434; 14566705; 28041799) of patients with leukodystrophy vanishing white matter who also have congenital cataracts with different homozygous or compound heterozygous variants in this gene.
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.138 ATP6V1A Ain Roesley gene: ATP6V1A was added
gene: ATP6V1A was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: ATP6V1A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP6V1A were set to PMID: 28065471
Phenotypes for gene: ATP6V1A were set to Cutis laxa, autosomal recessive, type IID (MIM# 617403)
Penetrance for gene: ATP6V1A were set to unknown
Review for gene: ATP6V1A was set to GREEN
Added comment: PMID: 28065471;
- 3 families (including 2 consanguineous) with homozygous missense
- in vitro assays using patients' fibroblasts demonstrated the variants disrupted V-ATPase complex assembly and stability
Sources: Literature
Cataract v0.176 CTDP1 Zornitza Stark edited their review of gene: CTDP1: Changed rating: GREEN
Cataract v0.176 CTDP1 Zornitza Stark edited their review of gene: CTDP1: Changed publications: 14517542, 24690360, 25529582
Cataract v0.176 CTDP1 Zornitza Stark Marked gene: CTDP1 as ready
Cataract v0.176 CTDP1 Zornitza Stark Gene: ctdp1 has been classified as Amber List (Moderate Evidence).
Cataract v0.176 CTDP1 Zornitza Stark Phenotypes for gene: CTDP1 were changed from to Congenital cataracts, facial dysmorphism, and neuropathy, MIM# 604168
Cataract v0.175 CTDP1 Zornitza Stark Publications for gene: CTDP1 were set to
Cataract v0.174 CTDP1 Zornitza Stark Mode of inheritance for gene: CTDP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cataract v0.173 CTDP1 Zornitza Stark Classified gene: CTDP1 as Amber List (moderate evidence)
Cataract v0.173 CTDP1 Zornitza Stark Gene: ctdp1 has been classified as Amber List (Moderate Evidence).
Cataract v0.172 CTDP1 Zornitza Stark Tag founder tag was added to gene: CTDP1.
Cataract v0.172 CTDP1 Zornitza Stark reviewed gene: CTDP1: Rating: AMBER; Mode of pathogenicity: None; Publications: 14517542, 24690360; Phenotypes: Congenital cataracts, facial dysmorphism, and neuropathy, MIM# 604168; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cataract v0.172 DYRK1A Zornitza Stark Marked gene: DYRK1A as ready
Cataract v0.172 DYRK1A Zornitza Stark Gene: dyrk1a has been classified as Red List (Low Evidence).
Cataract v0.172 DYRK1A Seb Lunke gene: DYRK1A was added
gene: DYRK1A was added to Cataract. Sources: Literature
Mode of inheritance for gene: DYRK1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DYRK1A were set to 28053047; 25944381
Phenotypes for gene: DYRK1A were set to congenital cataracts
Review for gene: DYRK1A was set to RED
Added comment: Really only one patient where cataract has been attributed directly to DYRK1A variant, 13 others with DYRK1A variants did not have cataracts (28053047). Second mention of cataract the gene was part of a large multi-gene deletion, and again other patients with DYRK1A (28053047) variants did not have cataract. Insufficient evidence.
Sources: Literature
Mendeliome v0.3265 DNMBP Seb Lunke Marked gene: DNMBP as ready
Mendeliome v0.3265 DNMBP Seb Lunke Gene: dnmbp has been classified as Green List (High Evidence).
Mendeliome v0.3265 DNMBP Seb Lunke Classified gene: DNMBP as Green List (high evidence)
Mendeliome v0.3265 DNMBP Seb Lunke Gene: dnmbp has been classified as Green List (High Evidence).
Mendeliome v0.3264 DNMBP Seb Lunke gene: DNMBP was added
gene: DNMBP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DNMBP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNMBP were set to 30290152
Phenotypes for gene: DNMBP were set to congenital cataract
Review for gene: DNMBP was set to GREEN
gene: DNMBP was marked as current diagnostic
Added comment: Multiple individuals from three independent large consanguineous families with bilateral infantile cataracts. Seperate hom nonsense variants.
Sources: Literature
Cataract v0.171 DNMBP Seb Lunke Marked gene: DNMBP as ready
Cataract v0.171 DNMBP Seb Lunke Gene: dnmbp has been classified as Green List (High Evidence).
Cataract v0.171 DNMBP Seb Lunke Classified gene: DNMBP as Green List (high evidence)
Cataract v0.171 DNMBP Seb Lunke Gene: dnmbp has been classified as Green List (High Evidence).
Cataract v0.170 DNMBP Seb Lunke gene: DNMBP was added
gene: DNMBP was added to Cataract. Sources: Literature
Mode of inheritance for gene: DNMBP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNMBP were set to 30290152
Phenotypes for gene: DNMBP were set to congenital cataract
Review for gene: DNMBP was set to GREEN
gene: DNMBP was marked as current diagnostic
Added comment: Multiple individuals from three independent large consanguineous families with bilateral infantile cataracts. Seperate hom nonsense variants.
Sources: Literature
Differences of Sex Development v0.34 WDR11 Teresa Zhao reviewed gene: WDR11: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20887964, PMID: 29263200; Phenotypes: Hypogonadotropic hypogonadism 14 with or without anosmia, MIM#614858; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.3263 CRYGA Zornitza Stark Marked gene: CRYGA as ready
Mendeliome v0.3263 CRYGA Zornitza Stark Gene: cryga has been classified as Red List (Low Evidence).
Mendeliome v0.3263 CRYGA Zornitza Stark gene: CRYGA was added
gene: CRYGA was added to Mendeliome. Sources: Expert list
refuted tags were added to gene: CRYGA.
Mode of inheritance for gene: CRYGA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CRYGA were set to 30450742; 28839118
Phenotypes for gene: CRYGA were set to Cataract
Review for gene: CRYGA was set to RED
Added comment: Reported as potentially disease causing in multiple individuals from two seperate families, but in both cases variant is present in the general population (20 Hets for one variant, >1000 hets and 9 homs in other variant)
Sources: Expert list
Cataract v0.169 CRYGA Seb Lunke Tag refuted was removed from gene: CRYGA.
Tag disputed tag was added to gene: CRYGA.
Cataract v0.169 CRYGA Zornitza Stark Tag refuted tag was added to gene: CRYGA.
Mendeliome v0.3262 AKR1E2 Zornitza Stark Marked gene: AKR1E2 as ready
Mendeliome v0.3262 AKR1E2 Zornitza Stark Gene: akr1e2 has been classified as Red List (Low Evidence).
Mendeliome v0.3262 AKR1E2 Zornitza Stark gene: AKR1E2 was added
gene: AKR1E2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: AKR1E2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AKR1E2 were set to 26622071
Phenotypes for gene: AKR1E2 were set to congenital cataracts
Review for gene: AKR1E2 was set to RED
Added comment: Same family with homozygous canonical splice variants and 3 cases of congenital cataract described in 2012 (original) and 2015 (review). No other descriptions since.
Sources: Expert list
Cataract v0.169 ADAMTSL4 Zornitza Stark Marked gene: ADAMTSL4 as ready
Cataract v0.169 ADAMTSL4 Zornitza Stark Gene: adamtsl4 has been classified as Red List (Low Evidence).
Mendeliome v0.3261 ADAMTSL4 Zornitza Stark Marked gene: ADAMTSL4 as ready
Mendeliome v0.3261 ADAMTSL4 Zornitza Stark Gene: adamtsl4 has been classified as Green List (High Evidence).
Mendeliome v0.3261 ADAMTSL4 Zornitza Stark Phenotypes for gene: ADAMTSL4 were changed from to Ectopia lentis, isolated, autosomal recessive, MIM# 225100
Mendeliome v0.3260 ADAMTSL4 Zornitza Stark Publications for gene: ADAMTSL4 were set to
Mendeliome v0.3259 ADAMTSL4 Zornitza Stark Mode of inheritance for gene: ADAMTSL4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3258 ADAMTSL4 Zornitza Stark Tag founder tag was added to gene: ADAMTSL4.
Mendeliome v0.3258 ADAMTSL4 Zornitza Stark reviewed gene: ADAMTSL4: Rating: GREEN; Mode of pathogenicity: None; Publications: 19200529, 20564469, 20141359, 21051722; Phenotypes: Ectopia lentis, isolated, autosomal recessive, MIM# 225100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cataract v0.169 ADAMTSL4 Zornitza Stark reviewed gene: ADAMTSL4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Cataract v0.169 ABHD12 Zornitza Stark Phenotypes for gene: ABHD12 were changed from Polyneuropathy; Hearing loss; Ataxia; Retinitis pigmentosa; Cataracts to Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract, MIM# 612674
Cataract v0.168 ABHD12 Zornitza Stark reviewed gene: ABHD12: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract, MIM# 612674; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3258 HIST1H4C Zornitza Stark Marked gene: HIST1H4C as ready
Mendeliome v0.3258 HIST1H4C Zornitza Stark Gene: hist1h4c has been classified as Green List (High Evidence).
Mendeliome v0.3258 HIST1H4C Zornitza Stark Phenotypes for gene: HIST1H4C were changed from to Growth delay, microcephaly and intellectual disability
Mendeliome v0.3257 HIST1H4C Zornitza Stark Publications for gene: HIST1H4C were set to
Mendeliome v0.3256 HIST1H4C Zornitza Stark Mode of inheritance for gene: HIST1H4C was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3255 HIST1H4C Zornitza Stark reviewed gene: HIST1H4C: Rating: GREEN; Mode of pathogenicity: None; Publications: 28920961; Phenotypes: Growth delay, microcephaly and intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cataract v0.168 CRYGA Seb Lunke Marked gene: CRYGA as ready
Cataract v0.168 CRYGA Seb Lunke Gene: cryga has been classified as Red List (Low Evidence).
Cataract v0.168 CRYGA Seb Lunke gene: CRYGA was added
gene: CRYGA was added to Cataract. Sources: Literature
Mode of inheritance for gene: CRYGA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CRYGA were set to 30450742; 28839118
Review for gene: CRYGA was set to RED
Added comment: Reported as potentially disease causing in multiple individuals from two seperate families, but in both cases variant is present in the general population (20 Hets for one variant, >1000 hets and 9 homs in other variant)
Sources: Literature
Microcephaly v0.139 HIST1H4C Zornitza Stark Marked gene: HIST1H4C as ready
Microcephaly v0.139 HIST1H4C Zornitza Stark Gene: hist1h4c has been classified as Green List (High Evidence).
Microcephaly v0.139 HIST1H4C Zornitza Stark Phenotypes for gene: HIST1H4C were changed from to Growth delay, microcephaly and intellectual disability
Microcephaly v0.138 HIST1H4C Zornitza Stark Publications for gene: HIST1H4C were set to
Microcephaly v0.137 HIST1H4C Zornitza Stark Mode of inheritance for gene: HIST1H4C was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.136 HIST1H4C Zornitza Stark reviewed gene: HIST1H4C: Rating: GREEN; Mode of pathogenicity: None; Publications: 28920961; Phenotypes: Growth delay, microcephaly and intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cataract v0.167 AKR1E2 Seb Lunke Marked gene: AKR1E2 as ready
Cataract v0.167 AKR1E2 Seb Lunke Gene: akr1e2 has been classified as Red List (Low Evidence).
Cataract v0.167 AKR1E2 Seb Lunke gene: AKR1E2 was added
gene: AKR1E2 was added to Cataract. Sources: Literature
Mode of inheritance for gene: AKR1E2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AKR1E2 were set to 26622071; 26622071
Phenotypes for gene: AKR1E2 were set to congenital cararact
Review for gene: AKR1E2 was set to RED
Added comment: Same family with homozygous canonical splice variants and 3 cases of congenital cataract described in 2012 (original) and 2015 (review). No other descriptions since.
Sources: Literature
Cataract v0.166 ADAMTSL4 Seb Lunke gene: ADAMTSL4 was added
gene: ADAMTSL4 was added to Cataract. Sources: Literature
Mode of inheritance for gene: ADAMTSL4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAMTSL4 were set to 22338190; 20702823
Phenotypes for gene: ADAMTSL4 were set to ectopia lentis; cataract
Review for gene: ADAMTSL4 was set to RED
Added comment: Early onset cataract described in multiple patients with variants in ADAMTSL4 as a secondary manifestation to Ectopia lentis et pupillae (MIM 225200)
Sources: Literature
Cataract v0.165 ABHD12 Seb Lunke Marked gene: ABHD12 as ready
Cataract v0.165 ABHD12 Seb Lunke Gene: abhd12 has been classified as Green List (High Evidence).
Cataract v0.165 ABHD12 Seb Lunke Classified gene: ABHD12 as Green List (high evidence)
Cataract v0.165 ABHD12 Seb Lunke Gene: abhd12 has been classified as Green List (High Evidence).
Cataract v0.164 ABHD12 Seb Lunke gene: ABHD12 was added
gene: ABHD12 was added to Cataract. Sources: Literature
Mode of inheritance for gene: ABHD12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABHD12 were set to 32077159; 29571850; 28448692; 24697911
Phenotypes for gene: ABHD12 were set to Polyneuropathy; Hearing loss; Ataxia; Retinitis pigmentosa; Cataracts
Added comment: Two siblings each from two families with hom nonsense and PHARC syndrome and early on-set cataract, and a complex homozygous nonsense variant in an adult with early on-set cataract have been descibed recently in addition to original mutations described in 11 families from 4 different countries (Fiskerstrand et al (2010)). Total over 10 independent cases mentioned in literature.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2737 HIST1H4C Seb Lunke Classified gene: HIST1H4C as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2737 HIST1H4C Seb Lunke Gene: hist1h4c has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2736 HIST1H4C Seb Lunke reviewed gene: HIST1H4C: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Cataract v0.162 PLOD3 Zornitza Stark edited their review of gene: PLOD3: Changed rating: GREEN
Cataract v0.162 PLOD3 Zornitza Stark edited their review of gene: PLOD3: Changed phenotypes: Lysyl hydroxylase 3 deficiency, MIM#612394
Cataract v0.162 POLG Zornitza Stark Marked gene: POLG as ready
Cataract v0.162 POLG Zornitza Stark Gene: polg has been classified as Green List (High Evidence).
Cataract v0.162 POLG Zornitza Stark Phenotypes for gene: POLG were changed from to POLG-related disorders
Cataract v0.161 POLG Zornitza Stark Publications for gene: POLG were set to
Cataract v0.160 POLG Zornitza Stark Mode of inheritance for gene: POLG was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cataract v0.159 POLG Zornitza Stark reviewed gene: POLG: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301791, 29358615, 22405928; Phenotypes: POLG-related disorders; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cataract v0.159 RIC1 Zornitza Stark Marked gene: RIC1 as ready
Cataract v0.159 RIC1 Zornitza Stark Gene: ric1 has been classified as Amber List (Moderate Evidence).
Cataract v0.159 RIC1 Zornitza Stark Classified gene: RIC1 as Amber List (moderate evidence)
Cataract v0.159 RIC1 Zornitza Stark Gene: ric1 has been classified as Amber List (Moderate Evidence).
Cataract v0.158 RIC1 Zornitza Stark gene: RIC1 was added
gene: RIC1 was added to Cataract. Sources: Expert list
Mode of inheritance for gene: RIC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RIC1 were set to 27878435; 31932796
Phenotypes for gene: RIC1 were set to CATIFA syndrome, MIM# 618761
Review for gene: RIC1 was set to AMBER
Added comment: 8 individuals from two consanguineous families, homozygous for same missense variant (founder effect). Cataract is a key feature of the phenotype.
Sources: Expert list
Cataract v0.157 SLC16A12 Zornitza Stark Marked gene: SLC16A12 as ready
Cataract v0.157 SLC16A12 Zornitza Stark Gene: slc16a12 has been classified as Green List (High Evidence).
Cataract v0.157 SLC16A12 Zornitza Stark Phenotypes for gene: SLC16A12 were changed from to Cataract 47, juvenile, with microcornea 612018
Cataract v0.156 SLC16A12 Zornitza Stark Publications for gene: SLC16A12 were set to
Cataract v0.155 SLC16A12 Zornitza Stark Mode of inheritance for gene: SLC16A12 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cataract v0.154 SLC16A12 Zornitza Stark reviewed gene: SLC16A12: Rating: GREEN; Mode of pathogenicity: None; Publications: 20181839, 21778275, 18304496, 29088427; Phenotypes: Cataract 47, juvenile, with microcornea 612018; Mode of inheritance: None
Cataract v0.154 WFS1 Zornitza Stark Marked gene: WFS1 as ready
Cataract v0.154 WFS1 Zornitza Stark Gene: wfs1 has been classified as Green List (High Evidence).
Cataract v0.154 WFS1 Zornitza Stark Classified gene: WFS1 as Green List (high evidence)
Cataract v0.154 WFS1 Zornitza Stark Gene: wfs1 has been classified as Green List (High Evidence).
Cataract v0.153 WFS1 Zornitza Stark gene: WFS1 was added
gene: WFS1 was added to Cataract. Sources: Expert list
Mode of inheritance for gene: WFS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WFS1 were set to 32350710
Phenotypes for gene: WFS1 were set to Wolfram syndrome 1, MIM# 222300
Review for gene: WFS1 was set to GREEN
Added comment: Cataracts reported in ~40% in a cohort of affected individuals.
Sources: Expert list
Cataract v0.152 XYLT2 Zornitza Stark Marked gene: XYLT2 as ready
Cataract v0.152 XYLT2 Zornitza Stark Gene: xylt2 has been classified as Green List (High Evidence).
Cataract v0.152 XYLT2 Zornitza Stark Classified gene: XYLT2 as Green List (high evidence)
Cataract v0.152 XYLT2 Zornitza Stark Gene: xylt2 has been classified as Green List (High Evidence).
Cataract v0.151 XYLT2 Zornitza Stark gene: XYLT2 was added
gene: XYLT2 was added to Cataract. Sources: Expert list
Mode of inheritance for gene: XYLT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: XYLT2 were set to 26027496
Phenotypes for gene: XYLT2 were set to Spondyloocular syndrome, MIM# 605822
Review for gene: XYLT2 was set to GREEN
Added comment: Cataracts are a key feature of this condition.
Sources: Expert list
Deafness_IsolatedAndComplex v0.360 PNPT1 Zornitza Stark edited their review of gene: PNPT1: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.360 PNPT1 Zornitza Stark Mode of inheritance for gene: PNPT1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.359 PNPT1 Zornitza Stark Publications for gene: PNPT1 were set to 23084290; 31752325
Deafness_IsolatedAndComplex v0.358 PNPT1 Zornitza Stark edited their review of gene: PNPT1: Changed rating: GREEN
Deafness_IsolatedAndComplex v0.358 PNPT1 Lilian Downie reviewed gene: PNPT1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 30244537; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.71 TOR1A Zornitza Stark Marked gene: TOR1A as ready
Arthrogryposis v0.71 TOR1A Zornitza Stark Gene: tor1a has been classified as Green List (High Evidence).
Arthrogryposis v0.71 TOR1A Zornitza Stark Classified gene: TOR1A as Green List (high evidence)
Arthrogryposis v0.71 TOR1A Zornitza Stark Gene: tor1a has been classified as Green List (High Evidence).
Bleeding and Platelet Disorders v0.23 RASGRP2 Zornitza Stark Marked gene: RASGRP2 as ready
Bleeding and Platelet Disorders v0.23 RASGRP2 Zornitza Stark Gene: rasgrp2 has been classified as Green List (High Evidence).
Arthrogryposis v0.70 TOR1A Michelle Torres changed review comment from: 5 patients reported by multiple authors supporting that biallelic mutations (missense, inframe del and protein truncating) in TOR1A cause severe arthrogryposis. Other variable features are developmental delay, strabismus and tremor. Parents carriers do not have symptoms of autosomal dominant dystonia, also associate with this gene and known to have incomplete penetrance (OMIM).
Sources: Literature; to: 5 families reported by multiple authors supporting that biallelic mutations (missense, inframe del and protein truncating) in TOR1A cause severe arthrogryposis. Other variable features are developmental delay, strabismus and tremor. Parents carriers do not have symptoms of autosomal dominant dystonia, also associate with this gene and known to have incomplete penetrance (OMIM).
Sources: Literature
Bleeding and Platelet Disorders v0.23 RASGRP2 Zornitza Stark Classified gene: RASGRP2 as Green List (high evidence)
Bleeding and Platelet Disorders v0.23 RASGRP2 Zornitza Stark Gene: rasgrp2 has been classified as Green List (High Evidence).
Bleeding and Platelet Disorders v0.22 RASGRP2 Zornitza Stark gene: RASGRP2 was added
gene: RASGRP2 was added to Bleeding Disorders. Sources: Literature
Mode of inheritance for gene: RASGRP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RASGRP2 were set to 24958846; 32609603; 32041177; 31724816; 30849270
Phenotypes for gene: RASGRP2 were set to Bleeding disorder, platelet-type, 18, MIM# 615888
Review for gene: RASGRP2 was set to GREEN
Added comment: Multiple affected families reported.
Sources: Literature
Ciliary Dyskinesia v0.121 OFD1 Zornitza Stark Phenotypes for gene: OFD1 were changed from Joubert syndrome 10, MIM 300804; Orofaciodigital syndrome I, MIM 311200; Simpson-Golabi-Behmel syndrome, type 2, MIM 300209 to Joubert syndrome 10, MIM 300804; Orofaciodigital syndrome I, MIM 311200; Simpson-Golabi-Behmel syndrome, type 2, MIM 300209; Primary ciliary dyskinesia
Ciliary Dyskinesia v0.120 OFD1 Zornitza Stark Classified gene: OFD1 as Green List (high evidence)
Ciliary Dyskinesia v0.120 OFD1 Zornitza Stark Gene: ofd1 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.119 OFD1 Zornitza Stark changed review comment from: The conditions associated with this gene are not primary ciliary dyskinesias. Gene is appropriate for Ciliopathy panel. However, note 3 individuals reported with PCD phenotype.; to: The conditions associated with this gene are not primary ciliary dyskinesias. Gene is appropriate for Ciliopathy panel. However, note 7 individuals reported with PCD phenotype.
Ciliary Dyskinesia v0.119 OFD1 Zornitza Stark edited their review of gene: OFD1: Changed rating: GREEN
Ciliary Dyskinesia v0.119 OFD1 Zornitza Stark edited their review of gene: OFD1: Changed publications: 31366608, 31373179
Ciliary Dyskinesia v0.119 OFD1 Zornitza Stark Classified gene: OFD1 as Amber List (moderate evidence)
Ciliary Dyskinesia v0.119 OFD1 Zornitza Stark Gene: ofd1 has been classified as Amber List (Moderate Evidence).
Ciliary Dyskinesia v0.118 OFD1 Zornitza Stark edited their review of gene: OFD1: Changed publications: 31373179
Ciliary Dyskinesia v0.118 OFD1 Zornitza Stark changed review comment from: The conditions associated with this gene are not primary ciliary dyskinesias. Gene is appropriate for Ciliopathy panel.; to: The conditions associated with this gene are not primary ciliary dyskinesias. Gene is appropriate for Ciliopathy panel. However, note 3 individuals reported with PCD phenotype.
Ciliary Dyskinesia v0.118 OFD1 Zornitza Stark edited their review of gene: OFD1: Changed phenotypes: Retinitis pigmentosa 23, MIM# 300424, Joubert syndrome 10, MIM# 300804, Orofaciodigital syndrome I, MIM# 311200, Primary ciliary dyskinesia
Ciliary Dyskinesia v0.118 OFD1 Zornitza Stark edited their review of gene: OFD1: Changed rating: AMBER
Mendeliome v0.3255 SFTPA1 Zornitza Stark Marked gene: SFTPA1 as ready
Mendeliome v0.3255 SFTPA1 Zornitza Stark Gene: sftpa1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3255 SFTPA1 Zornitza Stark Phenotypes for gene: SFTPA1 were changed from to Idiopathic pulmonary fibrosis
Mendeliome v0.3254 SFTPA1 Zornitza Stark Publications for gene: SFTPA1 were set to
Mendeliome v0.3253 SFTPA1 Zornitza Stark Mode of inheritance for gene: SFTPA1 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.3252 SFTPA1 Zornitza Stark Classified gene: SFTPA1 as Amber List (moderate evidence)
Mendeliome v0.3252 SFTPA1 Zornitza Stark Gene: sftpa1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3251 SFTPA1 Zornitza Stark reviewed gene: SFTPA1: Rating: AMBER; Mode of pathogenicity: None; Publications: 31601679, 30854216, 28869238, 26792177; Phenotypes: Idiopathic pulmonary fibrosis; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Pulmonary Fibrosis_Interstitial Lung Disease v0.6 SFTPA1 Zornitza Stark Marked gene: SFTPA1 as ready
Pulmonary Fibrosis_Interstitial Lung Disease v0.6 SFTPA1 Zornitza Stark Gene: sftpa1 has been classified as Amber List (Moderate Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.6 SFTPA1 Zornitza Stark Classified gene: SFTPA1 as Amber List (moderate evidence)
Pulmonary Fibrosis_Interstitial Lung Disease v0.6 SFTPA1 Zornitza Stark Gene: sftpa1 has been classified as Amber List (Moderate Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.5 SFTPA1 Zornitza Stark gene: SFTPA1 was added
gene: SFTPA1 was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Literature
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 31601679; 30854216; 28869238; 26792177
Phenotypes for gene: SFTPA1 were set to Idiopathic pulmonary fibrosis
Review for gene: SFTPA1 was set to AMBER
Added comment: Four families and a mouse model, bi-allelic disease appears to be more severe, earlier onset.
Sources: Literature
Mendeliome v0.3251 CFAP74 Zornitza Stark Marked gene: CFAP74 as ready
Mendeliome v0.3251 CFAP74 Zornitza Stark Gene: cfap74 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3251 CFAP74 Zornitza Stark Classified gene: CFAP74 as Amber List (moderate evidence)
Mendeliome v0.3251 CFAP74 Zornitza Stark Gene: cfap74 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3250 CFAP74 Zornitza Stark gene: CFAP74 was added
gene: CFAP74 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CFAP74 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CFAP74 were set to 32555313
Phenotypes for gene: CFAP74 were set to Primary ciliary dyskinesia; infertility
Review for gene: CFAP74 was set to AMBER
Added comment: Two unrelated individuals with compound het missense variants reported.
Sources: Literature
Ciliary Dyskinesia v0.118 CFAP74 Zornitza Stark Marked gene: CFAP74 as ready
Ciliary Dyskinesia v0.118 CFAP74 Zornitza Stark Gene: cfap74 has been classified as Amber List (Moderate Evidence).
Ciliary Dyskinesia v0.118 CFAP74 Zornitza Stark Classified gene: CFAP74 as Amber List (moderate evidence)
Ciliary Dyskinesia v0.118 CFAP74 Zornitza Stark Gene: cfap74 has been classified as Amber List (Moderate Evidence).
Ciliary Dyskinesia v0.117 CFAP74 Zornitza Stark gene: CFAP74 was added
gene: CFAP74 was added to Ciliary Dyskinesia. Sources: Literature
Mode of inheritance for gene: CFAP74 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CFAP74 were set to 32555313
Phenotypes for gene: CFAP74 were set to Primary ciliary dyskinesia; infertility
Review for gene: CFAP74 was set to AMBER
Added comment: Two unrelated individuals with compound het missense variants reported.
Sources: Literature
Hereditary Spastic Paraplegia - paediatric v0.113 Zornitza Stark removed gene:STUB1 from the panel
Hereditary Spastic Paraplegia - adult onset v0.23 Zornitza Stark removed gene:STUB1 from the panel
Hereditary Neuropathy - complex v0.73 STUB1 Zornitza Stark Classified gene: STUB1 as Green List (high evidence)
Hereditary Neuropathy - complex v0.73 STUB1 Zornitza Stark Gene: stub1 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.72 STUB1 Zornitza Stark gene: STUB1 was added
gene: STUB1 was added to Hereditary Neuropathy - complex. Sources: Literature
Mode of inheritance for gene: STUB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STUB1 were set to 32342324; 32337344
Phenotypes for gene: STUB1 were set to Spinocerebellar ataxia, autosomal recessive 16, MIM# 615768
Review for gene: STUB1 was set to GREEN
Added comment: PMID: 32342324 - Gene causes both AD and AR spinocerebellar ataxia. Reviews 17 families (31 patients, adolescent/childhood onset), all patients developed progressive cerebellar ataxia, associated with dysmetria and dysarthria, corticospinal signs (19/31), myoclonus (7/31) and generalized tonic– clonic seizures (4/31), peripheral nervous system involvement (4/12). PMID: 32337344 - 1 large family with adult-onset gait disturbance and cognitive decline. Neuropathy is a feature of the more severe, bi-allelic disorder.
Sources: Literature
Hereditary Spastic Paraplegia - paediatric v0.112 STUB1 Zornitza Stark Classified gene: STUB1 as Green List (high evidence)
Hereditary Spastic Paraplegia - paediatric v0.112 STUB1 Zornitza Stark Gene: stub1 has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.80 LAMB1 Zornitza Stark Publications for gene: LAMB1 were set to
Leukodystrophy - adult onset v0.79 LAMB1 Zornitza Stark edited their review of gene: LAMB1: Changed rating: RED; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Leukodystrophy - adult onset v0.79 LAMB1 Zornitza Stark reviewed gene: LAMB1: Rating: ; Mode of pathogenicity: None; Publications: 32548278; Phenotypes: ; Mode of inheritance: None
Arthrogryposis v0.70 TOR1A Michelle Torres gene: TOR1A was added
gene: TOR1A was added to Arthrogryposis. Sources: Literature
Mode of inheritance for gene: TOR1A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TOR1A were set to PMID: 30244176
Phenotypes for gene: TOR1A were set to Arthrogryposis
Review for gene: TOR1A was set to GREEN
Added comment: 5 patients reported by multiple authors supporting that biallelic mutations (missense, inframe del and protein truncating) in TOR1A cause severe arthrogryposis. Other variable features are developmental delay, strabismus and tremor. Parents carriers do not have symptoms of autosomal dominant dystonia, also associate with this gene and known to have incomplete penetrance (OMIM).
Sources: Literature
Ataxia - adult onset v0.64 STUB1 Zornitza Stark Marked gene: STUB1 as ready
Ataxia - adult onset v0.64 STUB1 Zornitza Stark Gene: stub1 has been classified as Green List (High Evidence).
Ataxia - adult onset v0.64 STUB1 Zornitza Stark Phenotypes for gene: STUB1 were changed from Autosomal recessive spinocerebellar ataxia type 16, 615768; Spinocerebellar ataxia, autosomal recessive 16 to Spinocerebellar ataxia 48, MIM#618093
Ataxia - adult onset v0.63 STUB1 Zornitza Stark Publications for gene: STUB1 were set to
Ataxia - adult onset v0.62 STUB1 Zornitza Stark Mode of inheritance for gene: STUB1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ichthyosis v0.82 SREBF1 Zornitza Stark Marked gene: SREBF1 as ready
Ichthyosis v0.82 SREBF1 Zornitza Stark Gene: srebf1 has been classified as Green List (High Evidence).
Ichthyosis v0.82 SREBF1 Zornitza Stark Classified gene: SREBF1 as Green List (high evidence)
Ichthyosis v0.82 SREBF1 Zornitza Stark Gene: srebf1 has been classified as Green List (High Evidence).
Ichthyosis v0.81 SREBF1 Zornitza Stark gene: SREBF1 was added
gene: SREBF1 was added to Ichthyosis. Sources: Literature
Mode of inheritance for gene: SREBF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SREBF1 were set to 32497488
Phenotypes for gene: SREBF1 were set to IFAP (ichthyosis follicularis, atrichia, and photophobia) syndrome
Review for gene: SREBF1 was set to GREEN
Added comment: 11 unrelated, ethnically diverse individuals with autosomal-dominant IFAP syndrome. 3 different msisense variants identified affecting the same region (residues 527, 528, and 530). Functional studies support impaired function (impaired nuclear translocation of the transcriptionally active form of SREBP1 resulting in lower expression of the SREBP1 variants). Increased keratinocyte apoptosis was observed in patient scalp samples.
Sources: Literature
Palmoplantar Keratoderma and Erythrokeratoderma v0.8 ASPRV1 Zornitza Stark Marked gene: ASPRV1 as ready
Palmoplantar Keratoderma and Erythrokeratoderma v0.8 ASPRV1 Zornitza Stark Gene: asprv1 has been classified as Green List (High Evidence).
Palmoplantar Keratoderma and Erythrokeratoderma v0.8 ASPRV1 Zornitza Stark Classified gene: ASPRV1 as Green List (high evidence)
Palmoplantar Keratoderma and Erythrokeratoderma v0.8 ASPRV1 Zornitza Stark Gene: asprv1 has been classified as Green List (High Evidence).
Mendeliome v0.3249 ASPRV1 Zornitza Stark Marked gene: ASPRV1 as ready
Mendeliome v0.3249 ASPRV1 Zornitza Stark Gene: asprv1 has been classified as Green List (High Evidence).
Mendeliome v0.3249 ASPRV1 Zornitza Stark Classified gene: ASPRV1 as Green List (high evidence)
Mendeliome v0.3249 ASPRV1 Zornitza Stark Gene: asprv1 has been classified as Green List (High Evidence).
Palmoplantar Keratoderma and Erythrokeratoderma v0.7 ASPRV1 Ee Ming Wong gene: ASPRV1 was added
gene: ASPRV1 was added to Palmoplantar Keratoderma and Erythrokeratoderma. Sources: Literature
Mode of inheritance for gene: ASPRV1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ASPRV1 were set to PMID: 32516568
Phenotypes for gene: ASPRV1 were set to palmoplantar keratoderma; lamellar ichthyosis
Review for gene: ASPRV1 was set to GREEN
gene: ASPRV1 was marked as current diagnostic
Added comment: -3 heterozygous missense variants identified across 4 unrelated kindreds
-mutant ASPRV1 expressed in human keratinocytes suggests impaired filaggrin processing
Sources: Literature
Mendeliome v0.3248 ASPRV1 Ee Ming Wong gene: ASPRV1 was added
gene: ASPRV1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ASPRV1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ASPRV1 were set to PMID: 32516568
Phenotypes for gene: ASPRV1 were set to palmoplantar keratoderma; lamellar ichthyosis
Review for gene: ASPRV1 was set to GREEN
gene: ASPRV1 was marked as current diagnostic
Added comment: -3 heterozygous missense variants identified across 4 unrelated kindreds
-mutant ASPRV1 expressed in human keratinocytes suggests impaired filaggrin processing
Sources: Literature
Mitochondrial disease v0.449 MT-CO3 Zornitza Stark Marked gene: MT-CO3 as ready
Mitochondrial disease v0.449 MT-CO3 Zornitza Stark Gene: mt-co3 has been classified as Green List (High Evidence).
Mitochondrial disease v0.449 MT-CO3 Zornitza Stark Classified gene: MT-CO3 as Green List (high evidence)
Mitochondrial disease v0.449 MT-CO3 Zornitza Stark Gene: mt-co3 has been classified as Green List (High Evidence).
Mendeliome v0.3248 LGR4 Zornitza Stark Marked gene: LGR4 as ready
Mendeliome v0.3248 LGR4 Zornitza Stark Gene: lgr4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3248 LGR4 Zornitza Stark Publications for gene: LGR4 were set to
Mendeliome v0.3247 LGR4 Zornitza Stark Phenotypes for gene: LGR4 were changed from to Delayed puberty
Ichthyosis v0.80 ASPRV1 Zornitza Stark Marked gene: ASPRV1 as ready
Ichthyosis v0.80 ASPRV1 Zornitza Stark Gene: asprv1 has been classified as Green List (High Evidence).
Ichthyosis v0.80 ASPRV1 Zornitza Stark Classified gene: ASPRV1 as Green List (high evidence)
Ichthyosis v0.80 ASPRV1 Zornitza Stark Gene: asprv1 has been classified as Green List (High Evidence).
Mendeliome v0.3246 SREBF1 Seb Lunke Marked gene: SREBF1 as ready
Mendeliome v0.3246 SREBF1 Seb Lunke Gene: srebf1 has been classified as Green List (High Evidence).
Mendeliome v0.3246 SREBF1 Seb Lunke Classified gene: SREBF1 as Green List (high evidence)
Mendeliome v0.3246 SREBF1 Seb Lunke Gene: srebf1 has been classified as Green List (High Evidence).
Regression v0.126 TBCE Zornitza Stark Marked gene: TBCE as ready
Regression v0.126 TBCE Zornitza Stark Gene: tbce has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2736 CNOT1 Chern Lim reviewed gene: CNOT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32553196; Phenotypes: Neurodevelopmental delay; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Regression v0.126 TBCE Zornitza Stark Classified gene: TBCE as Green List (high evidence)
Regression v0.126 TBCE Zornitza Stark Gene: tbce has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - paediatric v0.111 TBCE Zornitza Stark Marked gene: TBCE as ready
Hereditary Spastic Paraplegia - paediatric v0.111 TBCE Zornitza Stark Gene: tbce has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - paediatric v0.111 TBCE Zornitza Stark Classified gene: TBCE as Green List (high evidence)
Hereditary Spastic Paraplegia - paediatric v0.111 TBCE Zornitza Stark Gene: tbce has been classified as Green List (High Evidence).
Mendeliome v0.3245 BTG4 Seb Lunke Marked gene: BTG4 as ready
Mendeliome v0.3245 BTG4 Seb Lunke Gene: btg4 has been classified as Green List (High Evidence).
Mendeliome v0.3245 BTG4 Seb Lunke Classified gene: BTG4 as Green List (high evidence)
Mendeliome v0.3245 BTG4 Seb Lunke Gene: btg4 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - adult onset v0.22 STUB1 Zornitza Stark Marked gene: STUB1 as ready
Hereditary Spastic Paraplegia - adult onset v0.22 STUB1 Zornitza Stark Gene: stub1 has been classified as Amber List (Moderate Evidence).
Hereditary Spastic Paraplegia - adult onset v0.22 STUB1 Zornitza Stark Classified gene: STUB1 as Amber List (moderate evidence)
Hereditary Spastic Paraplegia - adult onset v0.22 STUB1 Zornitza Stark Gene: stub1 has been classified as Amber List (Moderate Evidence).
Ataxia - adult onset v0.61 STUB1 Teresa Zhao reviewed gene: STUB1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32337344, PMID: 30381368, PMID: 31126790; Phenotypes: Spinocerebellar ataxia 48, MIM#618093; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.3244 TRIP13 Seb Lunke Marked gene: TRIP13 as ready
Mendeliome v0.3244 TRIP13 Seb Lunke Gene: trip13 has been classified as Green List (High Evidence).
Mendeliome v0.3244 LGR4 Zornitza Stark Mode of inheritance for gene: LGR4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3243 LGR4 Zornitza Stark Classified gene: LGR4 as Amber List (moderate evidence)
Mendeliome v0.3243 LGR4 Zornitza Stark Gene: lgr4 has been classified as Amber List (Moderate Evidence).
Gastrointestinal neuromuscular disease v0.27 L1CAM Bryony Thompson changed review comment from: At least 6 male cases in 5 unrelated families reported with hydrocephalus with Hirchsprung disease.
Sources: Expert list; to: At least 6 male cases in 5 unrelated families reported with hydrocephalus and Hirchsprung disease/intestinal pseudo-obstruction.
Sources: Expert list
Leukodystrophy - adult onset v0.79 LAMB1 Seb Lunke Marked gene: LAMB1 as ready
Leukodystrophy - adult onset v0.79 LAMB1 Seb Lunke Gene: lamb1 has been classified as Red List (Low Evidence).
Leukodystrophy - adult onset v0.79 LAMB1 Seb Lunke gene: LAMB1 was added
gene: LAMB1 was added to Leukodystrophy - adult onset. Sources: Literature
Mode of inheritance for gene: LAMB1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: LAMB1 were set to Retinal Vascular Abnormality; mild intellectual disability; white matter lesions; lower limb spasticity
Review for gene: LAMB1 was set to RED
Added comment: Single adult female patient with onset of symptoms after 22yrs of age. Novel homozygous missense variant in a distantly related family identified in exome sequencing, no further evidence of pathogenicity.
Sources: Literature
Leukodystrophy - paediatric v0.168 LAMB1 Zornitza Stark Marked gene: LAMB1 as ready
Leukodystrophy - paediatric v0.168 LAMB1 Zornitza Stark Gene: lamb1 has been classified as Amber List (Moderate Evidence).
Leukodystrophy - paediatric v0.168 LAMB1 Zornitza Stark Classified gene: LAMB1 as Amber List (moderate evidence)
Leukodystrophy - paediatric v0.168 LAMB1 Zornitza Stark Gene: lamb1 has been classified as Amber List (Moderate Evidence).
Leukodystrophy - paediatric v0.167 LAMB1 Zornitza Stark gene: LAMB1 was added
gene: LAMB1 was added to Leukodystrophy - paediatric. Sources: Literature
Mode of inheritance for gene: LAMB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LAMB1 were set to 29888467; 25925986
Phenotypes for gene: LAMB1 were set to Cystic leukoencephalopathy
Review for gene: LAMB1 was set to AMBER
Added comment: Two unrelated families reported with cystic leukoencephalopathy and bi-allelic variants in this gene. Also note adult-onset leukodystrophy reported in one individual.
Sources: Literature
Gastrointestinal neuromuscular disease v0.27 L1CAM Bryony Thompson Marked gene: L1CAM as ready
Gastrointestinal neuromuscular disease v0.27 L1CAM Bryony Thompson Gene: l1cam has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v0.27 L1CAM Bryony Thompson Classified gene: L1CAM as Green List (high evidence)
Gastrointestinal neuromuscular disease v0.27 L1CAM Bryony Thompson Gene: l1cam has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v0.26 L1CAM Bryony Thompson gene: L1CAM was added
gene: L1CAM was added to Gastrointestinal neuromuscular disease. Sources: Expert list
Mode of inheritance for gene: L1CAM was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: L1CAM were set to 9279760; 11857550; 15148591; 15368500; 22354677
Phenotypes for gene: L1CAM were set to Hydrocephalus with Hirschsprung disease or congenital idiopathic intestinal pseudoobstruction MIM#307000
Review for gene: L1CAM was set to GREEN
Added comment: At least 6 male cases in 5 unrelated families reported with hydrocephalus with Hirchsprung disease.
Sources: Expert list
Regression v0.125 TBCE Elena Savva gene: TBCE was added
gene: TBCE was added to Regression. Sources: Literature
Mode of inheritance for gene: TBCE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBCE were set to PMID: 27666369
Phenotypes for gene: TBCE were set to Encephalopathy, progressive, with amyotrophy and optic atrophy 617207
Review for gene: TBCE was set to GREEN
Added comment: PMID: 27666369 - 6 patients (4 families) with early-onset, progressive neurodegeneration encephalopathy with spinal muscular atrophy, supported by functional studies. Patients present within the first 18 months of life, phenotypes include hypotonia (3/6), dev delay (6/6), signs of regression (6/6, distal amyotrophy, ataxia, spasticity)
Missense variant p.I155N is recurring, very rare in gnomAD.
Sources: Literature
Ichthyosis v0.79 ASPRV1 Ee Ming Wong gene: ASPRV1 was added
gene: ASPRV1 was added to Ichthyosis. Sources: Literature
Mode of inheritance for gene: ASPRV1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ASPRV1 were set to PMID: 32516568
Phenotypes for gene: ASPRV1 were set to palmoplantar keratoderma; lamellar ichthyosis
Review for gene: ASPRV1 was set to GREEN
gene: ASPRV1 was marked as current diagnostic
Added comment: -3 heterozygous missense variants identified across 4 unrelated kindreds
-mutant ASPRV1 expressed in human keratinocytes suggests impaired filaggrin processing
Sources: Literature
Mendeliome v0.3242 SREBF1 Paul De Fazio gene: SREBF1 was added
gene: SREBF1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SREBF1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SREBF1 were set to 32497488
Phenotypes for gene: SREBF1 were set to IFAP (ichthyosis follicularis, atrichia, and photophobia) syndrome
Review for gene: SREBF1 was set to GREEN
gene: SREBF1 was marked as current diagnostic
Added comment: 11 unrelated, ethnically diverse individuals with autosomal-dominant IFAP syndrome. 3 different msisense variants identified affecting the same region (residues 527, 528, and 530). Functional studies support impaired function (impaired nuclear translocation of the transcriptionally active form of SREBP1 resulting in lower expression of the SREBP1 variants). Increased keratinocyte apoptosis was observed in patient scalp samples.
Sources: Literature
Hereditary Spastic Paraplegia - paediatric v0.110 TBCE Elena Savva gene: TBCE was added
gene: TBCE was added to Hereditary Spastic Paraplegia - paediatric. Sources: Expert list
Mode of inheritance for gene: TBCE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBCE were set to PMID: 27666369
Phenotypes for gene: TBCE were set to Encephalopathy, progressive, with amyotrophy and optic atrophy 617207
Review for gene: TBCE was set to GREEN
Added comment: PMID: 27666369 - 6 patients (4 families) with early-onset, progressive neurodegeneration encephalopathy with spinal muscular atrophy, supported by functional studies.
Patients present within the first 18 months of life, phenotypes include hypotonia (3/6), dev delay (6/6), signs of regression (6/6, distal amyotrophy, ataxia, spasticity)

Missense variant p.I155N is recurring, very rare in gnomAD.
Sources: Expert list
Mendeliome v0.3242 CNOT1 Chern Lim reviewed gene: CNOT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32553196; Phenotypes: Neurodevelopmental delay; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.3242 RAP1GDS1 Zornitza Stark Marked gene: RAP1GDS1 as ready
Mendeliome v0.3242 RAP1GDS1 Zornitza Stark Gene: rap1gds1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3242 RAP1GDS1 Zornitza Stark Classified gene: RAP1GDS1 as Amber List (moderate evidence)
Mendeliome v0.3242 RAP1GDS1 Zornitza Stark Gene: rap1gds1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3241 BTG4 Ain Roesley edited their review of gene: BTG4: Changed rating: GREEN
Hereditary Spastic Paraplegia - adult onset v0.21 STUB1 Elena Savva gene: STUB1 was added
gene: STUB1 was added to Hereditary Spastic Paraplegia - adult onset. Sources: Expert list
Mode of inheritance for gene: STUB1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: STUB1 were set to PMID: 32342324; 32337344
Phenotypes for gene: STUB1 were set to ?Spinocerebellar ataxia 48 618093; Spinocerebellar ataxia, autosomal recessive 16 615768
Review for gene: STUB1 was set to AMBER
Added comment: PMID: 32342324 - Gene causes both AD and AR spinocerebellar ataxia. Reviews 17 families (31 patients, adolescent/childhood onset), all patients developed progressive cerebellar ataxia, associated with dysmetria and dysarthria, corticospinal signs (19/31), myoclonus (7/31) and generalized tonic–clonic seizures (4/31), peripheral nervous system involvement (4/12).

PMID: 32337344 - 1 large family with adult-onset gait disturbance and cognitive decline
Sources: Expert list
Mendeliome v0.3241 BTG4 Ain Roesley gene: BTG4 was added
gene: BTG4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BTG4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BTG4 were set to PMID: 32502391
Phenotypes for gene: BTG4 were set to Zygotic cleavage failure (ZCF)
Penetrance for gene: BTG4 were set to unknown
Added comment: PMID: 32502391
- 4 affecteds from 4 families including 3 consanguineous families. 3 PTVs + 1 splice.
- in vitro assays in HELA cells showed all PTVs had complete loss of protein. The missense variant had abolished interaction with CNOT7
- In vivo studies further demonstrated that the process of maternal mRNA decay was disrupted in the zygotes of the affected individuals, which provides a mechanistic explanation for the phenotype of ZCF
Sources: Literature
Hereditary Spastic Paraplegia - paediatric v0.110 STUB1 Elena Savva gene: STUB1 was added
gene: STUB1 was added to Hereditary Spastic Paraplegia - paediatric. Sources: Expert list
Mode of inheritance for gene: STUB1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: STUB1 were set to PMID: 32342324; 32337344
Phenotypes for gene: STUB1 were set to ?Spinocerebellar ataxia 48 618093; Spinocerebellar ataxia, autosomal recessive 16 615768
Review for gene: STUB1 was set to GREEN
Added comment: PMID: 32342324 - Gene causes both AD and AR spinocerebellar ataxia. Reviews 17 families (31 patients, adolescent/childhood onset), all patients developed progressive cerebellar ataxia, associated with dysmetria and dysarthria, corticospinal signs (19/31), myoclonus (7/31) and generalized tonic–
clonic seizures (4/31), peripheral nervous system involvement (4/12).

PMID: 32337344 - 1 large family with adult-onset gait disturbance and cognitive decline
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2736 SLC12A2 Seb Lunke Phenotypes for gene: SLC12A2 were changed from Kilquist syndrome; deafness; intellectual disability; dysmorphic features; absent salivation to Kilquist syndrome; deafness; intellectual disability; dysmorphic features; absent salivation; ectodermal dysplasia; constipation; intestinal malrotation; multiple congenital anomalies
Intellectual disability syndromic and non-syndromic v0.2735 SLC12A2 Seb Lunke Classified gene: SLC12A2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2735 SLC12A2 Seb Lunke Added comment: Comment on list classification: Two independent families and mouse model
Intellectual disability syndromic and non-syndromic v0.2735 SLC12A2 Seb Lunke Gene: slc12a2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2734 SLC12A2 Seb Lunke reviewed gene: SLC12A2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ectodermal dysplasia, constipation, intestinal malrotation, multiple congenital anomalies; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.3241 KIAA1217 Zornitza Stark Marked gene: KIAA1217 as ready
Mendeliome v0.3241 KIAA1217 Zornitza Stark Gene: kiaa1217 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3241 KIAA1217 Zornitza Stark Classified gene: KIAA1217 as Amber List (moderate evidence)
Mendeliome v0.3241 KIAA1217 Zornitza Stark Gene: kiaa1217 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3240 KIAA1217 Zornitza Stark gene: KIAA1217 was added
gene: KIAA1217 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KIAA1217 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIAA1217 were set to 32369272
Phenotypes for gene: KIAA1217 were set to Vertebral anomalies, syndromic and non-syndromic
Review for gene: KIAA1217 was set to AMBER
Added comment: 10 families reported, however note only 3 of the variants were absent from gnomad, inheritance not reported, most variants are missense.
Sources: Literature
Mendeliome v0.3239 TRIP13 Ain Roesley reviewed gene: TRIP13: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32473092; Phenotypes: female infertility; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.19 TRIP13 Ain Roesley Deleted their review
Mendeliome v0.3239 LGR4 Elena Savva reviewed gene: LGR4: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 32493844; Phenotypes: {Bone mineral density, low, susceptibility to} 615311; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.19 TRIP13 Ain Roesley gene: TRIP13 was added
gene: TRIP13 was added to Amenorrhoea. Sources: Literature
Mode of inheritance for gene: TRIP13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRIP13 were set to PMID: 32473092
Phenotypes for gene: TRIP13 were set to female infertility
Penetrance for gene: TRIP13 were set to unknown
Review for gene: TRIP13 was set to GREEN
Added comment: PMID: 32473092;
- 5 patients from 4 families (including 1 consanguineous) diagnosed with primary infertility with normal menstrual cycles.
- all missense variants
Sources: Literature
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.19 IL17RD Lauren Akesson reviewed gene: IL17RD: Rating: RED; Mode of pathogenicity: None; Publications: 32389901, 23643382; Phenotypes: Hypogonadotropic hypogonadism 18 with or without anosmia (MIM# 615267); Mode of inheritance: Unknown
Mendeliome v0.3239 RAP1GDS1 Zornitza Stark gene: RAP1GDS1 was added
gene: RAP1GDS1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RAP1GDS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAP1GDS1 were set to 32431071
Phenotypes for gene: RAP1GDS1 were set to Intellectual disability; dysmorphic features
Review for gene: RAP1GDS1 was set to AMBER
Added comment: Four individuals from two consanguineous families, same homozygous splice site variant detected.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2734 RAP1GDS1 Zornitza Stark Marked gene: RAP1GDS1 as ready
Intellectual disability syndromic and non-syndromic v0.2734 RAP1GDS1 Zornitza Stark Gene: rap1gds1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2734 RAP1GDS1 Zornitza Stark Classified gene: RAP1GDS1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2734 RAP1GDS1 Zornitza Stark Gene: rap1gds1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2733 RAP1GDS1 Zornitza Stark gene: RAP1GDS1 was added
gene: RAP1GDS1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: RAP1GDS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAP1GDS1 were set to 32431071
Phenotypes for gene: RAP1GDS1 were set to Intellectual disability; dysmorphic features
Review for gene: RAP1GDS1 was set to AMBER
Added comment: Four individuals from two consanguineous families, same homozygous splice site variant detected.
Sources: Literature
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.19 HS6ST1 Lauren Akesson reviewed gene: HS6ST1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: Unknown
Mendeliome v0.3238 HOXD10 Zornitza Stark reviewed gene: HOXD10: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.3238 HOXD10 Zornitza Stark Marked gene: HOXD10 as ready
Mendeliome v0.3238 HOXD10 Zornitza Stark Gene: hoxd10 has been classified as Red List (Low Evidence).
Mendeliome v0.3238 HOXD10 Zornitza Stark Phenotypes for gene: HOXD10 were changed from to Charcot-Marie-Tooth disease, foot deformity of; Vertical talus, congenital (MIM#192950)
Mendeliome v0.3237 HOXD10 Zornitza Stark Publications for gene: HOXD10 were set to
Hereditary Neuropathy - complex v0.71 SGPL1 Zornitza Stark Marked gene: SGPL1 as ready
Hereditary Neuropathy - complex v0.71 SGPL1 Zornitza Stark Gene: sgpl1 has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy - complex v0.71 SGPL1 Zornitza Stark Classified gene: SGPL1 as Amber List (moderate evidence)
Hereditary Neuropathy - complex v0.71 SGPL1 Zornitza Stark Gene: sgpl1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3236 HOXD10 Zornitza Stark Mode of inheritance for gene: HOXD10 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3235 HOXD10 Zornitza Stark Classified gene: HOXD10 as Red List (low evidence)
Mendeliome v0.3235 HOXD10 Zornitza Stark Gene: hoxd10 has been classified as Red List (Low Evidence).
Cerebral Palsy v0.18 ADD3 Zornitza Stark Marked gene: ADD3 as ready
Cerebral Palsy v0.18 ADD3 Zornitza Stark Gene: add3 has been classified as Green List (High Evidence).
Cerebral Palsy v0.18 ADD3 Zornitza Stark Classified gene: ADD3 as Green List (high evidence)
Cerebral Palsy v0.18 ADD3 Zornitza Stark Gene: add3 has been classified as Green List (High Evidence).
Cataract v0.150 ADD3 Zornitza Stark Marked gene: ADD3 as ready
Cataract v0.150 ADD3 Zornitza Stark Gene: add3 has been classified as Amber List (Moderate Evidence).
Cataract v0.150 ADD3 Zornitza Stark Classified gene: ADD3 as Amber List (moderate evidence)
Cataract v0.150 ADD3 Zornitza Stark Gene: add3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3234 HOXD10 Crystle Lee reviewed gene: HOXD10: Rating: AMBER; Mode of pathogenicity: None; Publications: 15146389, 16450407; Phenotypes: Charcot-Marie-Tooth disease, foot deformity of, Vertical talus, congenital (MIM#192950); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Cerebral Palsy v0.17 ADD3 Zornitza Stark gene: ADD3 was added
gene: ADD3 was added to Cerebral Palsy. Sources: Expert Review
Mode of inheritance for gene: ADD3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADD3 were set to 23836506; 29768408
Phenotypes for gene: ADD3 were set to Cerebral palsy, spastic quadriplegic, 3 617008
Review for gene: ADD3 was set to GREEN
Added comment: Four families reported.
Sources: Expert Review
Microcephaly v0.136 ADD3 Zornitza Stark Marked gene: ADD3 as ready
Microcephaly v0.136 ADD3 Zornitza Stark Added comment: Comment when marking as ready: Microcephaly is borderline.
Microcephaly v0.136 ADD3 Zornitza Stark Gene: add3 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.136 ADD3 Zornitza Stark Marked gene: ADD3 as ready
Microcephaly v0.136 ADD3 Zornitza Stark Gene: add3 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.136 ADD3 Zornitza Stark Classified gene: ADD3 as Amber List (moderate evidence)
Microcephaly v0.136 ADD3 Zornitza Stark Gene: add3 has been classified as Amber List (Moderate Evidence).
Early-onset Parkinson disease v0.33 ATP6AP2 Zornitza Stark Marked gene: ATP6AP2 as ready
Early-onset Parkinson disease v0.33 ATP6AP2 Zornitza Stark Gene: atp6ap2 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.33 ATP6AP2 Zornitza Stark Classified gene: ATP6AP2 as Green List (high evidence)
Early-onset Parkinson disease v0.33 ATP6AP2 Zornitza Stark Gene: atp6ap2 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.70 Zornitza Stark removed gene:ATP6AP2 from the panel
Early-onset Parkinson disease v0.32 ATP6AP2 Zornitza Stark gene: ATP6AP2 was added
gene: ATP6AP2 was added to Early-onset Parkinson disease. Sources: Expert list
Mode of inheritance for gene: ATP6AP2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ATP6AP2 were set to 30985297; 23595882
Phenotypes for gene: ATP6AP2 were set to Parkinsonism with spasticity, X-linked, MIM# 300911
Review for gene: ATP6AP2 was set to GREEN
Added comment: PMID: 30985297 - 1 de novo male patient with postnatal neurodegeneration, seizures, mild face dysmorphism. Sequential MRI revealed decreasing gray and white matter volumes. Patient has a splice variant proven to cause alternative transcript expression. Supported by null mouse model.

PMID: 23595882 - 2 patients (1 family) with a synonymous variant proven to affect splicing. Patients have X-linked parkinsonian syndrome

Summary: 2 unrelated patients + animal models
Sources: Expert list
Macrocephaly_Megalencephaly v0.42 CACNA1E Zornitza Stark Marked gene: CACNA1E as ready
Macrocephaly_Megalencephaly v0.42 CACNA1E Zornitza Stark Gene: cacna1e has been classified as Green List (High Evidence).
Macrocephaly_Megalencephaly v0.42 CACNA1E Zornitza Stark Classified gene: CACNA1E as Green List (high evidence)
Macrocephaly_Megalencephaly v0.42 CACNA1E Zornitza Stark Gene: cacna1e has been classified as Green List (High Evidence).
Arthrogryposis v0.70 CACNA1E Zornitza Stark Marked gene: CACNA1E as ready
Arthrogryposis v0.70 CACNA1E Zornitza Stark Gene: cacna1e has been classified as Green List (High Evidence).
Arthrogryposis v0.70 CACNA1E Zornitza Stark Classified gene: CACNA1E as Green List (high evidence)
Arthrogryposis v0.70 CACNA1E Zornitza Stark Gene: cacna1e has been classified as Green List (High Evidence).
Regression v0.125 CACNA1E Zornitza Stark Marked gene: CACNA1E as ready
Regression v0.125 CACNA1E Zornitza Stark Gene: cacna1e has been classified as Green List (High Evidence).
Regression v0.125 CACNA1E Zornitza Stark Classified gene: CACNA1E as Green List (high evidence)
Regression v0.125 CACNA1E Zornitza Stark Gene: cacna1e has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - paediatric v0.110 GLRX5 Zornitza Stark reviewed gene: GLRX5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spasticity, childhood-onset, with hyperglycinemia, MIM# 616859; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Spastic Paraplegia - paediatric v0.110 GLRX5 Zornitza Stark Marked gene: GLRX5 as ready
Hereditary Spastic Paraplegia - paediatric v0.110 GLRX5 Zornitza Stark Gene: glrx5 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - paediatric v0.110 GLRX5 Zornitza Stark Classified gene: GLRX5 as Green List (high evidence)
Hereditary Spastic Paraplegia - paediatric v0.110 GLRX5 Zornitza Stark Gene: glrx5 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - paediatric v0.109 GLRX5 Zornitza Stark Classified gene: GLRX5 as Amber List (moderate evidence)
Hereditary Spastic Paraplegia - paediatric v0.109 GLRX5 Zornitza Stark Gene: glrx5 has been classified as Amber List (Moderate Evidence).
Leukodystrophy - paediatric v0.166 GLRX5 Zornitza Stark Marked gene: GLRX5 as ready
Leukodystrophy - paediatric v0.166 GLRX5 Zornitza Stark Gene: glrx5 has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.166 GLRX5 Zornitza Stark Classified gene: GLRX5 as Green List (high evidence)
Leukodystrophy - paediatric v0.166 GLRX5 Zornitza Stark Gene: glrx5 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.741 ADPRHL2 Zornitza Stark Marked gene: ADPRHL2 as ready
Genetic Epilepsy v0.741 ADPRHL2 Zornitza Stark Gene: adprhl2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.741 ADPRHL2 Zornitza Stark Phenotypes for gene: ADPRHL2 were changed from to Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures (MIM#618170)
Genetic Epilepsy v0.740 ADPRHL2 Zornitza Stark Publications for gene: ADPRHL2 were set to
Genetic Epilepsy v0.739 ADPRHL2 Zornitza Stark Mode of inheritance for gene: ADPRHL2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.738 GRN Zornitza Stark Marked gene: GRN as ready
Genetic Epilepsy v0.738 GRN Zornitza Stark Gene: grn has been classified as Green List (High Evidence).
Genetic Epilepsy v0.738 GRN Zornitza Stark Classified gene: GRN as Green List (high evidence)
Genetic Epilepsy v0.738 GRN Zornitza Stark Gene: grn has been classified as Green List (High Evidence).
Mendeliome v0.3234 ADPRHL2 Zornitza Stark Marked gene: ADPRHL2 as ready
Mendeliome v0.3234 ADPRHL2 Zornitza Stark Gene: adprhl2 has been classified as Green List (High Evidence).
Mendeliome v0.3234 ADPRHL2 Zornitza Stark Phenotypes for gene: ADPRHL2 were changed from to Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures, MIM#618170
Mendeliome v0.3233 ADPRHL2 Zornitza Stark Publications for gene: ADPRHL2 were set to
Hereditary Neuropathy - complex v0.69 SGPL1 Crystle Lee gene: SGPL1 was added
gene: SGPL1 was added to Hereditary Neuropathy - complex. Sources: Expert Review
Mode of inheritance for gene: SGPL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SGPL1 were set to 28077491; 28165339; 30274713; 28165343
Phenotypes for gene: SGPL1 were set to Nephrotic syndrome, type 14 (MIM#617575)
Review for gene: SGPL1 was set to AMBER
Added comment: Peripheral neuropathy has been reported in patients however does not appear to be consistent feature.

PMID: 28077491: Reported as a cause of CMT in 2 sibs

PMID: 28165339: Reported 7 families with SRNS and facultative ichthyosis, adrenal insufficiency, immunodeficiency, and neurological defects. Peripheral neuropathy (motor and sensory) reported in one family.

PMID: 30274713: Review article.
Sources: Expert Review
Mendeliome v0.3232 ADPRHL2 Zornitza Stark Mode of inheritance for gene: ADPRHL2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3231 ADPRHL2 Zornitza Stark edited their review of gene: ADPRHL2: Changed publications: 30100084, 30401461
Regression v0.124 ADPRHL2 Zornitza Stark Marked gene: ADPRHL2 as ready
Regression v0.124 ADPRHL2 Zornitza Stark Gene: adprhl2 has been classified as Green List (High Evidence).
Mendeliome v0.3231 ADPRHL2 Zornitza Stark changed review comment from: Ataxia is part of the phenotype.
Sources: Expert list; to: 14 families reported, onset is in the first years of life following normal early development. Patients have cyclic episodic deterioration in response to stress, such as infection or febrile illness. The severity is highly variable: some patients develop seizures early in life that are associated with loss of developmental milestones and early sudden death in childhood, whereas others present at a later age with muscle weakness, gait ataxia, impaired speech, more subtle clinical deterioration, and cognitive decline. Neurologic involvement includes gait ataxia, cerebellar signs associated with cerebellar atrophy, generalized brain atrophy, impaired intellectual development, hearing loss, and peripheral neuropathy.
Sources: Expert list
Regression v0.124 ADPRHL2 Zornitza Stark Classified gene: ADPRHL2 as Green List (high evidence)
Regression v0.124 ADPRHL2 Zornitza Stark Gene: adprhl2 has been classified as Green List (High Evidence).
Regression v0.123 ADPRHL2 Zornitza Stark gene: ADPRHL2 was added
gene: ADPRHL2 was added to Regression. Sources: Expert list
Mode of inheritance for gene: ADPRHL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADPRHL2 were set to 30100084; 30401461
Phenotypes for gene: ADPRHL2 were set to Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures, MIM# 618170
Review for gene: ADPRHL2 was set to GREEN
Added comment: 14 families reported, onset is in the first years of life following normal early development. Patients have cyclic episodic deterioration in response to stress, such as infection or febrile illness. The severity is highly variable: some patients develop seizures early in life that are associated with loss of developmental milestones and early sudden death in childhood, whereas others present at a later age with muscle weakness, gait ataxia, impaired speech, more subtle clinical deterioration, and cognitive decline. Neurologic involvement includes gait ataxia, cerebellar signs associated with cerebellar atrophy, generalized brain atrophy, impaired intellectual development, hearing loss, and peripheral neuropathy.
Sources: Expert list
Hereditary Neuropathy - complex v0.69 ADPRHL2 Zornitza Stark Marked gene: ADPRHL2 as ready
Hereditary Neuropathy - complex v0.69 ADPRHL2 Zornitza Stark Gene: adprhl2 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.69 ADPRHL2 Zornitza Stark Classified gene: ADPRHL2 as Green List (high evidence)
Hereditary Neuropathy - complex v0.69 ADPRHL2 Zornitza Stark Gene: adprhl2 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - paediatric v0.108 IRF2BPL Zornitza Stark Marked gene: IRF2BPL as ready
Hereditary Spastic Paraplegia - paediatric v0.108 IRF2BPL Zornitza Stark Gene: irf2bpl has been classified as Amber List (Moderate Evidence).
Hereditary Spastic Paraplegia - paediatric v0.108 IRF2BPL Zornitza Stark Classified gene: IRF2BPL as Amber List (moderate evidence)
Hereditary Spastic Paraplegia - paediatric v0.108 IRF2BPL Zornitza Stark Gene: irf2bpl has been classified as Amber List (Moderate Evidence).
Regression v0.122 IRF2BPL Zornitza Stark Marked gene: IRF2BPL as ready
Regression v0.122 IRF2BPL Zornitza Stark Gene: irf2bpl has been classified as Green List (High Evidence).
Regression v0.122 IRF2BPL Zornitza Stark Classified gene: IRF2BPL as Green List (high evidence)
Regression v0.122 IRF2BPL Zornitza Stark Gene: irf2bpl has been classified as Green List (High Evidence).
Dystonia - complex v0.70 IRF2BPL Zornitza Stark Marked gene: IRF2BPL as ready
Dystonia - complex v0.70 IRF2BPL Zornitza Stark Gene: irf2bpl has been classified as Green List (High Evidence).
Dystonia - complex v0.70 IRF2BPL Zornitza Stark Classified gene: IRF2BPL as Green List (high evidence)
Dystonia - complex v0.70 IRF2BPL Zornitza Stark Gene: irf2bpl has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - paediatric v0.107 MAPK8IP3 Zornitza Stark Marked gene: MAPK8IP3 as ready
Hereditary Spastic Paraplegia - paediatric v0.107 MAPK8IP3 Zornitza Stark Gene: mapk8ip3 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - paediatric v0.107 MAPK8IP3 Zornitza Stark Classified gene: MAPK8IP3 as Green List (high evidence)
Hereditary Spastic Paraplegia - paediatric v0.107 MAPK8IP3 Zornitza Stark Gene: mapk8ip3 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.68 FDX2 Zornitza Stark Marked gene: FDX2 as ready
Hereditary Neuropathy - complex v0.68 FDX2 Zornitza Stark Gene: fdx2 has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy - complex v0.68 FDX2 Zornitza Stark Classified gene: FDX2 as Amber List (moderate evidence)
Hereditary Neuropathy - complex v0.68 FDX2 Zornitza Stark Gene: fdx2 has been classified as Amber List (Moderate Evidence).
Hereditary Spastic Paraplegia - paediatric v0.106 RAB3GAP2 Zornitza Stark Marked gene: RAB3GAP2 as ready
Hereditary Spastic Paraplegia - paediatric v0.106 RAB3GAP2 Zornitza Stark Added comment: Comment when marking as ready: Syndromic spasticity.
Hereditary Spastic Paraplegia - paediatric v0.106 RAB3GAP2 Zornitza Stark Gene: rab3gap2 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - paediatric v0.106 RAB3GAP2 Zornitza Stark Classified gene: RAB3GAP2 as Green List (high evidence)
Hereditary Spastic Paraplegia - paediatric v0.106 RAB3GAP2 Zornitza Stark Gene: rab3gap2 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - paediatric v0.105 RAB3GAP2 Elena Savva gene: RAB3GAP2 was added
gene: RAB3GAP2 was added to Hereditary Spastic Paraplegia - paediatric. Sources: Literature
Mode of inheritance for gene: RAB3GAP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAB3GAP2 were set to PMID: 32376645
Phenotypes for gene: RAB3GAP2 were set to Martsolf syndrome 212720
Review for gene: RAB3GAP2 was set to GREEN
Added comment: PMID: 32376645 - 1 patient with bilateral clinodactyly and syndactyly, normal MRI and learning difficulties. Review of previous reports notes 9 additional patients (4 families) with Marsolf syndrome, with postnatal microcephaly (5/9), congenital cataracts (7/9), limb spasticity (7/9) and optic nerve atrophy (2/9).
Sources: Literature
Mendeliome v0.3231 GPR161 Zornitza Stark Marked gene: GPR161 as ready
Mendeliome v0.3231 GPR161 Zornitza Stark Gene: gpr161 has been classified as Green List (High Evidence).
Mendeliome v0.3231 GPR161 Zornitza Stark Classified gene: GPR161 as Green List (high evidence)
Mendeliome v0.3231 GPR161 Zornitza Stark Gene: gpr161 has been classified as Green List (High Evidence).
Mendeliome v0.3230 GPR161 Zornitza Stark gene: GPR161 was added
gene: GPR161 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GPR161 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GPR161 were set to 31609649
Phenotypes for gene: GPR161 were set to Predisposition to paediatric medulloblastoma
Review for gene: GPR161 was set to GREEN
Added comment: 6 unrelated individuals reported with germline variants, 5 with truncating, one missense. Somatic second hit in tumour tissue.
Sources: Literature
Hereditary Neuropathy - complex v0.67 FDX2 Crystle Lee gene: FDX2 was added
gene: FDX2 was added to Hereditary Neuropathy - complex. Sources: Expert Review
Mode of inheritance for gene: FDX2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FDX2 were set to 30010796; 24281368; 28803783
Phenotypes for gene: FDX2 were set to Mitochondrial myopathy, episodic, with optic atrophy and reversible leukoencephalopathy (MIM#251900)
Review for gene: FDX2 was set to AMBER
Added comment: Gene previously known as FDX1L. Limited evidence (1 family) suporting neuropathy being a feature of the associated condition

PMID: 30010796: Reported same variant in 2 apparently unrelated Brazilian families. Axonal
sensori-motor polyneuropathy reported in 4 out of the 6 patients. OMIM notes that peripheral neuropathy has onset in the second decade.
Sources: Expert Review
Hereditary Spastic Paraplegia - paediatric v0.105 MAPK8IP3 Elena Savva gene: MAPK8IP3 was added
gene: MAPK8IP3 was added to Hereditary Spastic Paraplegia - paediatric. Sources: Expert list
Mode of inheritance for gene: MAPK8IP3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MAPK8IP3 were set to PMID: 30612693; 30945334
Phenotypes for gene: MAPK8IP3 were set to Neurodevelopmental disorder with or without variable brain abnormalities 618443
Review for gene: MAPK8IP3 was set to GREEN
Added comment: PMID: 30612693 - 13 unrelated children patients with de novo variants, supported by functional studies. Patients have developmental delay (13/13), spasticity (4/13), ataxia (2/13), unstable gait (1/13), microcephaly (3/13), generalized seizures (3/13). No signs of regression, but cerebellar atrophy (3/12), thin corpus callosum (4/10), perisylvian polymicrogyria (2/12), white matter loss (4/12) was noted

PMID: 30945334 - 5 child patients (4 families) with spastic diplegia (4/5), ID (5/5), epilepsy (2/5) and cerebellar atrophy (5/5), corpus callosum hypoplasia (5/5). No regression.
Sources: Expert list
Dystonia - complex v0.69 IRF2BPL Elena Savva gene: IRF2BPL was added
gene: IRF2BPL was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: IRF2BPL was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: IRF2BPL were set to PMID: 30057031; 30166628
Phenotypes for gene: IRF2BPL were set to Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures 618088
Review for gene: IRF2BPL was set to GREEN
Added comment: PMID: 30057031 - 7 patients with neurodevelopmental regression (5/7), progressive ataxia (5/7), seizures (7/7), spasticity (2/7), dystonia (3/7) and global devel delay (7/7). PTCs produced a more severe phenotype than missense. Onset was in childhood. Cerebellar changes also less frequently reported.

PMID: 30166628 - 11 patients with de novo PTCs with childhood neurological regression, epilepsy (7/11), hypotonia (5/11), dystonia (3/11), cerebellar atrophy (5/10). MRI showed CNS defects in 6/10 patients.
Sources: Literature
Regression v0.121 IRF2BPL Elena Savva gene: IRF2BPL was added
gene: IRF2BPL was added to Regression. Sources: Literature
Mode of inheritance for gene: IRF2BPL was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: IRF2BPL were set to PMID: 30057031; 30166628
Phenotypes for gene: IRF2BPL were set to Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures 618088
Review for gene: IRF2BPL was set to GREEN
Added comment: PMID: 30057031 - 7 patients with neurodevelopmental regression (5/7), progressive ataxia (5/7), seizures (7/7), spasticity (2/7), dystonia (3/7) and global devel delay (7/7). PTCs produced a more severe phenotype than missense. Onset was in childhood. Cerebellar changes also less frequently reported.

PMID: 30166628 - 11 patients with de novo PTCs with childhood neurological regression, epilepsy (7/11), hypotonia (5/11), dystonia (3/11), cerebellar atrophy (5/10). MRI showed CNS defects in 6/10 patients.
Sources: Literature
Hereditary Spastic Paraplegia - paediatric v0.105 IRF2BPL Elena Savva gene: IRF2BPL was added
gene: IRF2BPL was added to Hereditary Spastic Paraplegia - paediatric. Sources: Expert list
Mode of inheritance for gene: IRF2BPL was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: IRF2BPL were set to PMID: 30057031; 30166628
Phenotypes for gene: IRF2BPL were set to Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures 618088
Review for gene: IRF2BPL was set to AMBER
Added comment: PMID: 30057031 - 7 patients with neurodevelopmental regression (5/7), progressive ataxia (5/7), seizures (7/7), spasticity (2/7), dystonia (3/7) and global devel delay (7/7). PTCs produced a more severe phenotype than missense. Onset was in childhood. Cerebellar changes also less frequently reported.

PMID: 30166628 - 11 patients with de novo PTCs with childhood neurological regression, epilepsy (7/11), hypotonia (5/11), dystonia (3/11), cerebellar atrophy (5/10). MRI showed CNS defects in 6/10 patients.
Sources: Expert list
Hereditary Neuropathy - complex v0.67 ADPRHL2 Crystle Lee gene: ADPRHL2 was added
gene: ADPRHL2 was added to Hereditary Neuropathy - complex. Sources: Expert Review
Mode of inheritance for gene: ADPRHL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADPRHL2 were set to 30100084; 30401461
Phenotypes for gene: ADPRHL2 were set to Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures (MIM#618170)
Review for gene: ADPRHL2 was set to GREEN
Added comment: Peripheral (sensori-)motor axonal neuropathy is a feature of this progressive neurodegenerative disorder. >5 families have been reported.
Sources: Expert Review
Genetic Epilepsy v0.737 GRN Elena Savva gene: GRN was added
gene: GRN was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: GRN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GRN were set to PMID: 22608501; 31855245
Phenotypes for gene: GRN were set to Ceroid lipofuscinosis, neuronal, 11 614706
Review for gene: GRN was set to GREEN
Added comment: PMID: 22608501 - 2 siblings with a homozygous PTC and neuronal ceroid lipofuscinosis. Both showed vision deterioration in their mid 20s, with MRI revealing cerebellar atrophy and ataxia

PMID: 31855245 - 6 patients (4 families) with homozygous PTCs and start-loss. 5/6 report vision impairement, 6/6 cognitive deterioration, 3/6 cerebellar involvement, 3/6 seizures. Reviews previous reports, age of onset varies from 7-56 years old and seizures reported in a total of 7/11 patients.
Sources: Literature
Genetic Epilepsy v0.737 ADPRHL2 Crystle Lee reviewed gene: ADPRHL2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30100084, 30401461; Phenotypes: Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures (MIM#618170); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cancer Predisposition_Paediatric v0.14 GPR161 Zornitza Stark Marked gene: GPR161 as ready
Cancer Predisposition_Paediatric v0.14 GPR161 Zornitza Stark Gene: gpr161 has been classified as Green List (High Evidence).
Cancer Predisposition_Paediatric v0.14 GPR161 Zornitza Stark Classified gene: GPR161 as Green List (high evidence)
Cancer Predisposition_Paediatric v0.14 GPR161 Zornitza Stark Gene: gpr161 has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.165 GLRX5 Elena Savva gene: GLRX5 was added
gene: GLRX5 was added to Leukodystrophy - paediatric. Sources: Literature
Mode of inheritance for gene: GLRX5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GLRX5 were set to PMID: 24334290; 30770271
Phenotypes for gene: GLRX5 were set to Spasticity, childhood-onset, with hyperglycinemia 616859
Review for gene: GLRX5 was set to GREEN
Added comment: PMID: 24334290 - 3 patients (3 families) with non-ketotic hyperglycinemia, supported by functional studies. Patients had normal development with childhood-onset spastic paraplegia (3/3), spinal lesion (1/3), optic atrophy (1/3) and brain signal abnormalities involving the frontal and parietal white matter (2/3)

PMID: 30770271 - 1 patient with childhood onset cavitating leukoencephalopathy.

p.Lys51del is a recurring mutation.
Sources: Literature
Hereditary Spastic Paraplegia - paediatric v0.105 GLRX5 Elena Savva gene: GLRX5 was added
gene: GLRX5 was added to Hereditary Spastic Paraplegia - paediatric. Sources: Expert list
Mode of inheritance for gene: GLRX5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GLRX5 were set to PMID: 24334290; 30770271
Phenotypes for gene: GLRX5 were set to Spasticity, childhood-onset, with hyperglycinemia 616859
Review for gene: GLRX5 was set to AMBER
Added comment: PMID: 24334290 - 3 patients (3 families) with non-ketotic hyperglycinemia, supported by functional studies. Patients had normal development with childhood-onset spastic paraplegia (3/3), spinal lesion (1/3), optic atrophy (1/3) and brain signal abnormalities involving the frontal and parietal white matter (2/3)

PMID: 30770271 - 1 patient with childhood onset cavitating leukoencephalopathy.

p.Lys51del is a recurring mutation.
Sources: Expert list
Regression v0.121 CACNA1E Elena Savva gene: CACNA1E was added
gene: CACNA1E was added to Regression. Sources: Literature
Mode of inheritance for gene: CACNA1E was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CACNA1E were set to PMID: 30343943
Phenotypes for gene: CACNA1E were set to Epileptic encephalopathy, early infantile, 69 618285
Mode of pathogenicity for gene: CACNA1E was set to Other
Review for gene: CACNA1E was set to GREEN
Added comment: PMID: 30343943 - 30 patients with de novo variants and early-onset developmental and epileptic encephalopathy. Patients had developmental regression (9/30), severe hypotonia (16/30), seizures (26/30), congenital joint contractures (13/30), macrocephaly (13/30). MRI shows white matter loss, cortical atrophy
Variants showed a GOF and LOF.
Sources: Literature
Arthrogryposis v0.69 CACNA1E Elena Savva gene: CACNA1E was added
gene: CACNA1E was added to Arthrogryposis. Sources: Literature
Mode of inheritance for gene: CACNA1E was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CACNA1E were set to PMID: 30343943
Phenotypes for gene: CACNA1E were set to Epileptic encephalopathy, early infantile, 69 618285
Mode of pathogenicity for gene: CACNA1E was set to Other
Added comment: PMID: 30343943 - 30 patients with de novo variants and early-onset developmental and epileptic encephalopathy. Patients had developmental regression (9/30), severe hypotonia (16/30), seizures (26/30), congenital joint contractures (13/30), macrocephaly (13/30). MRI shows white matter loss, cortical atrophy
Variants showed a GOF and LOF.
Sources: Literature
Macrocephaly_Megalencephaly v0.41 CACNA1E Elena Savva gene: CACNA1E was added
gene: CACNA1E was added to Macrocephaly_Megalencephaly. Sources: Literature
Mode of inheritance for gene: CACNA1E was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CACNA1E were set to PMID: 30343943
Phenotypes for gene: CACNA1E were set to Epileptic encephalopathy, early infantile, 69 618285
Mode of pathogenicity for gene: CACNA1E was set to Other
Review for gene: CACNA1E was set to GREEN
Added comment: PMID: 30343943 - 30 patients with de novo variants and early-onset developmental and epileptic encephalopathy. Patients had developmental regression (9/30), severe hypotonia (16/30), seizures (26/30), congenital joint contractures (13/30), macrocephaly (13/30). MRI shows white matter loss, cortical atrophy
Variants showed a GOF and LOF.
Sources: Literature
Hereditary Neuropathy - complex v0.67 ATP6AP2 Elena Savva gene: ATP6AP2 was added
gene: ATP6AP2 was added to Hereditary Neuropathy - complex. Sources: Expert list
Mode of inheritance for gene: ATP6AP2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ATP6AP2 were set to PMID: 30985297; 23595882
Phenotypes for gene: ATP6AP2 were set to ?Parkinsonism with spasticity, X-linked 300911
Review for gene: ATP6AP2 was set to GREEN
Added comment: PMID: 30985297 - 1 de novo male patient with postnatal neurodegeneration, seizures, mild face dysmorphism. Sequential MRI revealed decreasing gray and white matter volumes. Patient has a splice variant proven to cause alternative transcript expression. Supported by null mouse model.

PMID: 23595882 - 2 patients (1 family) with a synonymous variant proven to affect splicing. Patients have X-linked parkinsonian syndrome

Summary: 2 unrelated patients + animal models
Sources: Expert list
Cancer Predisposition_Paediatric v0.13 GPR161 Zornitza Stark gene: GPR161 was added
gene: GPR161 was added to Cancer Predisposition_Paediatric. Sources: Literature
Mode of inheritance for gene: GPR161 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GPR161 were set to 31609649
Phenotypes for gene: GPR161 were set to Predisposition to paediatric medulloblastoma
Review for gene: GPR161 was set to GREEN
Added comment: 6 unrelated individuals reported with germline variants, 5 with truncating, one missense. Somatic second hit in tumour tissue.
Sources: Literature
Microcephaly v0.135 ADD3 Elena Savva gene: ADD3 was added
gene: ADD3 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: ADD3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADD3 were set to PMID: 23836506; 29768408
Phenotypes for gene: ADD3 were set to Cerebral palsy, spastic quadriplegic, 3 617008
Review for gene: ADD3 was set to GREEN
Added comment: PMID: 29768408;23836506 - 9/10 patients (4 families) with borderline microcephaly
Sources: Literature
Cataract v0.149 ADD3 Elena Savva gene: ADD3 was added
gene: ADD3 was added to Cataract. Sources: Literature
Mode of inheritance for gene: ADD3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADD3 were set to PMID: 29768408; 23836506
Phenotypes for gene: ADD3 were set to Cerebral palsy, spastic quadriplegic, 3 617008
Review for gene: ADD3 was set to AMBER
Added comment: PMID: 29768408;23836506 - 4/5 patients (2 families) with early-onset bilateral cataracts

Two families, emerging gene
Sources: Literature
Mendeliome v0.3229 SETD1B Zornitza Stark Marked gene: SETD1B as ready
Mendeliome v0.3229 SETD1B Zornitza Stark Gene: setd1b has been classified as Green List (High Evidence).
Mendeliome v0.3229 SETD1B Zornitza Stark Phenotypes for gene: SETD1B were changed from to Epilepsy with myoclonic absences; intellectual disability; SETD1B-related neurodevelopmental disorder
Mendeliome v0.3228 SETD1B Zornitza Stark Publications for gene: SETD1B were set to
Mendeliome v0.3227 SETD1B Zornitza Stark Mode of inheritance for gene: SETD1B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3226 SETD1B Zornitza Stark reviewed gene: SETD1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 32546566, 29322246, 31440728, 31685013; Phenotypes: Epilepsy with myoclonic absences, intellectual disability, SETD1B-related neurodevelopmental disorder; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.737 SETD1B Zornitza Stark changed review comment from: At least 3, possibly 5, individuals reported with de novo variants in this gene and a neurodevelopmental disorder including seizures.; to: At least 7, possibly 9, individuals reported with de novo variants in this gene and a neurodevelopmental disorder including seizures.
Genetic Epilepsy v0.737 SETD1B Zornitza Stark edited their review of gene: SETD1B: Changed phenotypes: Epilepsy with myoclonic absences, intellectual disability, SETD1B-related neurodevelopmental disorder
Genetic Epilepsy v0.737 SETD1B Zornitza Stark edited their review of gene: SETD1B: Changed publications: 32546566, 29322246, 31440728, 31685013
Genetic Epilepsy v0.737 SETD1B Zornitza Stark Phenotypes for gene: SETD1B were changed from Epilepsy with myoclonic absences; intellectual disability to Epilepsy with myoclonic absences; intellectual disability; SETD1B-related neurodevelopmental disorder
Intellectual disability syndromic and non-syndromic v0.2732 SETD1B Zornitza Stark Publications for gene: SETD1B were set to 32546566
Intellectual disability syndromic and non-syndromic v0.2731 SETD1B Zornitza Stark changed review comment from: At least 4 unrelated individuals reported.; to: At least 7 unrelated individuals reported.
Intellectual disability syndromic and non-syndromic v0.2731 SETD1B Zornitza Stark edited their review of gene: SETD1B: Changed publications: 32546566, 29322246, 31440728, 31685013
Intellectual disability syndromic and non-syndromic v0.2731 SETD1B Zornitza Stark Marked gene: SETD1B as ready
Intellectual disability syndromic and non-syndromic v0.2731 SETD1B Zornitza Stark Gene: setd1b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2731 SETD1B Zornitza Stark Phenotypes for gene: SETD1B were changed from to SETD1B-related neurodevelopmental disorder
Intellectual disability syndromic and non-syndromic v0.2730 SETD1B Zornitza Stark Publications for gene: SETD1B were set to
Intellectual disability syndromic and non-syndromic v0.2729 SETD1B Zornitza Stark Mode of inheritance for gene: SETD1B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2728 SETD1B Zornitza Stark reviewed gene: SETD1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 32546566; Phenotypes: SETD1B-related neurodevelopmental disorder; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3226 ARF1 Zornitza Stark Marked gene: ARF1 as ready
Mendeliome v0.3226 ARF1 Zornitza Stark Gene: arf1 has been classified as Green List (High Evidence).
Mendeliome v0.3226 ARF1 Zornitza Stark Classified gene: ARF1 as Green List (high evidence)
Mendeliome v0.3226 ARF1 Zornitza Stark Gene: arf1 has been classified as Green List (High Evidence).
Mendeliome v0.3225 ARF1 Zornitza Stark gene: ARF1 was added
gene: ARF1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ARF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARF1 were set to 28868155
Phenotypes for gene: ARF1 were set to Periventricular nodular heterotopia 8, MIM# 618185
Review for gene: ARF1 was set to GREEN
Added comment: Three unrelated individuals reported with de novo missense in this gene.
Sources: Expert list
Periventricular Grey Matter Heterotopia v0.9 ARF1 Zornitza Stark Marked gene: ARF1 as ready
Periventricular Grey Matter Heterotopia v0.9 ARF1 Zornitza Stark Gene: arf1 has been classified as Green List (High Evidence).
Periventricular Grey Matter Heterotopia v0.9 ARF1 Zornitza Stark Classified gene: ARF1 as Green List (high evidence)
Periventricular Grey Matter Heterotopia v0.9 ARF1 Zornitza Stark Gene: arf1 has been classified as Green List (High Evidence).
Periventricular Grey Matter Heterotopia v0.8 ARF1 Zornitza Stark gene: ARF1 was added
gene: ARF1 was added to Periventricular Grey Matter Heterotopia. Sources: Expert list
Mode of inheritance for gene: ARF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARF1 were set to 28868155
Phenotypes for gene: ARF1 were set to Periventricular nodular heterotopia 8, MIM# 618185
Review for gene: ARF1 was set to GREEN
Added comment: Three unrelated individuals reported with de novo missense in this gene.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2728 MAP1B Zornitza Stark Phenotypes for gene: MAP1B were changed from Intellectual disability; seizures; PVNH; dysmorphic features to Intellectual disability; seizures; PVNH; dysmorphic features; Periventricular nodular heterotopia 9, MIM# 618918
Intellectual disability syndromic and non-syndromic v0.2727 MAP1B Zornitza Stark edited their review of gene: MAP1B: Changed phenotypes: Intellectual disability, seizures, PVNH, dysmorphic features, Periventricular nodular heterotopia 9, MIM# 618918
Polymicrogyria and Schizencephaly v0.89 MAP1B Zornitza Stark Phenotypes for gene: MAP1B were changed from Intellectual disability; seizures; PVNH; dysmorphic features to Intellectual disability; seizures; PVNH; dysmorphic features; Periventricular nodular heterotopia 9, MIM# 618918
Polymicrogyria and Schizencephaly v0.88 MAP1B Zornitza Stark edited their review of gene: MAP1B: Changed phenotypes: Intellectual disability, seizures, PVNH, dysmorphic features, Periventricular nodular heterotopia 9, MIM# 618918
Periventricular Grey Matter Heterotopia v0.7 MAP1B Zornitza Stark Marked gene: MAP1B as ready
Periventricular Grey Matter Heterotopia v0.7 MAP1B Zornitza Stark Gene: map1b has been classified as Green List (High Evidence).
Periventricular Grey Matter Heterotopia v0.7 MAP1B Zornitza Stark Phenotypes for gene: MAP1B were changed from to Intellectual disability; seizures; PVNH; dysmorphic features; Periventricular nodular heterotopia 9, MIM# 618918
Mendeliome v0.3224 MAP1B Zornitza Stark Phenotypes for gene: MAP1B were changed from Intellectual disability; seizures; PVNH; dysmorphic features to Intellectual disability; seizures; PVNH; dysmorphic features; Periventricular nodular heterotopia 9, MIM# 618918
Mendeliome v0.3223 MAP1B Zornitza Stark edited their review of gene: MAP1B: Changed phenotypes: Intellectual disability, seizures, PVNH, dysmorphic features, Periventricular nodular heterotopia 9, MIM# 618918
Periventricular Grey Matter Heterotopia v0.6 MAP1B Zornitza Stark Publications for gene: MAP1B were set to
Periventricular Grey Matter Heterotopia v0.5 MAP1B Zornitza Stark Mode of inheritance for gene: MAP1B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Periventricular Grey Matter Heterotopia v0.4 MAP1B Zornitza Stark edited their review of gene: MAP1B: Changed phenotypes: Intellectual disability, seizures, PVNH, dysmorphic features, Periventricular nodular heterotopia 9, MIM# 618918
Overgrowth v0.57 SUZ12 Zornitza Stark Marked gene: SUZ12 as ready
Overgrowth v0.57 SUZ12 Zornitza Stark Gene: suz12 has been classified as Green List (High Evidence).
Overgrowth v0.57 SUZ12 Zornitza Stark Phenotypes for gene: SUZ12 were changed from to Imagawa-Matsumoto syndrome, MIM# 618786
Overgrowth v0.56 SUZ12 Zornitza Stark Publications for gene: SUZ12 were set to
Overgrowth v0.55 SUZ12 Zornitza Stark Mode of inheritance for gene: SUZ12 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Overgrowth v0.54 SUZ12 Zornitza Stark reviewed gene: SUZ12: Rating: GREEN; Mode of pathogenicity: None; Publications: 31736240, 28229514; Phenotypes: Imagawa-Matsumoto syndrome, MIM# 618786; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Overgrowth v0.54 RNF125 Zornitza Stark changed review comment from: At least 3 unrelated families reported.; to: At least 3 unrelated families reported, overgrowth is a key feature.
Overgrowth v0.54 RNF125 Zornitza Stark Marked gene: RNF125 as ready
Overgrowth v0.54 RNF125 Zornitza Stark Gene: rnf125 has been classified as Green List (High Evidence).
Overgrowth v0.54 RNF125 Zornitza Stark Phenotypes for gene: RNF125 were changed from to Tenorio syndrome, MIM# 616260
Overgrowth v0.53 RNF125 Zornitza Stark Publications for gene: RNF125 were set to
Overgrowth v0.52 RNF125 Zornitza Stark Mode of inheritance for gene: RNF125 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Overgrowth v0.51 RNF125 Zornitza Stark reviewed gene: RNF125: Rating: GREEN; Mode of pathogenicity: None; Publications: 25196541; Phenotypes: Tenorio syndrome, MIM# 616260; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Overgrowth v0.51 PTCH1 Zornitza Stark Marked gene: PTCH1 as ready
Overgrowth v0.51 PTCH1 Zornitza Stark Gene: ptch1 has been classified as Red List (Low Evidence).
Overgrowth v0.51 PTCH1 Zornitza Stark Phenotypes for gene: PTCH1 were changed from to Basal cell nevus syndrome, MIM# 109400
Overgrowth v0.50 PTCH1 Zornitza Stark Classified gene: PTCH1 as Red List (low evidence)
Overgrowth v0.50 PTCH1 Zornitza Stark Gene: ptch1 has been classified as Red List (Low Evidence).
Overgrowth v0.49 PTCH1 Zornitza Stark reviewed gene: PTCH1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Basal cell nevus syndrome, MIM# 109400; Mode of inheritance: None
Overgrowth v0.49 PPP2R5D Zornitza Stark Marked gene: PPP2R5D as ready
Overgrowth v0.49 PPP2R5D Zornitza Stark Gene: ppp2r5d has been classified as Red List (Low Evidence).
Overgrowth v0.49 PPP2R5D Zornitza Stark Phenotypes for gene: PPP2R5D were changed from to Mental retardation, autosomal dominant 35, MIM# 616355
Overgrowth v0.48 PPP2R5D Zornitza Stark Publications for gene: PPP2R5D were set to
Overgrowth v0.47 PPP2R5D Zornitza Stark Mode of inheritance for gene: PPP2R5D was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Overgrowth v0.46 PPP2R5D Zornitza Stark Classified gene: PPP2R5D as Red List (low evidence)
Overgrowth v0.46 PPP2R5D Zornitza Stark Gene: ppp2r5d has been classified as Red List (Low Evidence).
Overgrowth v0.45 PPP2R5D Zornitza Stark reviewed gene: PPP2R5D: Rating: RED; Mode of pathogenicity: None; Publications: 26168268, 25972378, 25533962; Phenotypes: Mental retardation, autosomal dominant 35, MIM# 616355; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Overgrowth v0.45 PIK3CA Zornitza Stark Marked gene: PIK3CA as ready
Overgrowth v0.45 PIK3CA Zornitza Stark Gene: pik3ca has been classified as Green List (High Evidence).
Overgrowth v0.45 PIK3CA Zornitza Stark Phenotypes for gene: PIK3CA were changed from to Cowden syndrome 5, MIM# 615108
Overgrowth v0.44 PIK3CA Zornitza Stark Publications for gene: PIK3CA were set to
Overgrowth v0.43 PIK3CA Zornitza Stark Mode of inheritance for gene: PIK3CA was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Overgrowth v0.42 PIK3CA Zornitza Stark reviewed gene: PIK3CA: Rating: GREEN; Mode of pathogenicity: None; Publications: 23246288, 32362992, 31929958; Phenotypes: Cowden syndrome 5, MIM# 615108; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Overgrowth v0.42 PHF6 Zornitza Stark Marked gene: PHF6 as ready
Overgrowth v0.42 PHF6 Zornitza Stark Gene: phf6 has been classified as Red List (Low Evidence).
Overgrowth v0.42 PHF6 Zornitza Stark Phenotypes for gene: PHF6 were changed from to Borjeson-Forssman-Lehmann syndrome, MIM# 301900
Overgrowth v0.41 PHF6 Zornitza Stark Mode of inheritance for gene: PHF6 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Overgrowth v0.40 PHF6 Zornitza Stark Classified gene: PHF6 as Red List (low evidence)
Overgrowth v0.40 PHF6 Zornitza Stark Gene: phf6 has been classified as Red List (Low Evidence).
Overgrowth v0.39 PHF6 Zornitza Stark reviewed gene: PHF6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Borjeson-Forssman-Lehmann syndrome, MIM# 301900; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Overgrowth v0.39 PDGFRB Zornitza Stark Marked gene: PDGFRB as ready
Overgrowth v0.39 PDGFRB Zornitza Stark Gene: pdgfrb has been classified as Green List (High Evidence).
Overgrowth v0.39 PDGFRB Zornitza Stark Phenotypes for gene: PDGFRB were changed from to Kosaki overgrowth syndrome, MIM# 616592
Overgrowth v0.38 PDGFRB Zornitza Stark Publications for gene: PDGFRB were set to
Overgrowth v0.37 PDGFRB Zornitza Stark Mode of inheritance for gene: PDGFRB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Overgrowth v0.36 PDGFRB Zornitza Stark reviewed gene: PDGFRB: Rating: GREEN; Mode of pathogenicity: None; Publications: 25454926, 32291752, 30941910, 29226947; Phenotypes: Kosaki overgrowth syndrome, MIM# 616592; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Overgrowth v0.36 Zornitza Stark removed gene:NPR3 from the panel
Overgrowth v0.35 NPR3 Zornitza Stark changed review comment from: Four affected individuals from three unrelated families.; to: Four affected individuals from three unrelated families, however phenotype is more Marfanoid, rather than generalised overgrowth.
Overgrowth v0.35 NPR3 Zornitza Stark edited their review of gene: NPR3: Changed rating: AMBER
Overgrowth v0.35 MED12 Zornitza Stark Marked gene: MED12 as ready
Overgrowth v0.35 MED12 Zornitza Stark Gene: med12 has been classified as Amber List (Moderate Evidence).
Overgrowth v0.35 MED12 Zornitza Stark Phenotypes for gene: MED12 were changed from to Lujan-Fryns syndrome, MIM# 309520; Opitz-Kaveggia syndrome, MIM# 305450
Overgrowth v0.34 MED12 Zornitza Stark Mode of inheritance for gene: MED12 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Overgrowth v0.33 MED12 Zornitza Stark Classified gene: MED12 as Amber List (moderate evidence)
Overgrowth v0.33 MED12 Zornitza Stark Gene: med12 has been classified as Amber List (Moderate Evidence).
Overgrowth v0.32 MED12 Zornitza Stark reviewed gene: MED12: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Lujan-Fryns syndrome, MIM# 309520, Opitz-Kaveggia syndrome, MIM# 305450; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Overgrowth v0.32 KMT5B Zornitza Stark Classified gene: KMT5B as Amber List (moderate evidence)
Overgrowth v0.32 KMT5B Zornitza Stark Gene: kmt5b has been classified as Amber List (Moderate Evidence).
Overgrowth v0.31 KMT5B Zornitza Stark changed review comment from: Tendency towards taller height reported in some affected individuals.; to: Tendency towards taller height reported in some affected individuals, overgrowth is not a prominent/consistent feature.
Overgrowth v0.31 KMT5B Zornitza Stark edited their review of gene: KMT5B: Changed rating: AMBER
Overgrowth v0.31 GLI3 Zornitza Stark Marked gene: GLI3 as ready
Overgrowth v0.31 GLI3 Zornitza Stark Gene: gli3 has been classified as Amber List (Moderate Evidence).
Overgrowth v0.31 GLI3 Zornitza Stark Classified gene: GLI3 as Amber List (moderate evidence)
Overgrowth v0.31 GLI3 Zornitza Stark Gene: gli3 has been classified as Amber List (Moderate Evidence).
Overgrowth v0.30 GLI3 Zornitza Stark reviewed gene: GLI3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Overgrowth v0.30 DIS3L2 Zornitza Stark Tag SV/CNV tag was added to gene: DIS3L2.
Overgrowth v0.30 DIS3L2 Zornitza Stark Marked gene: DIS3L2 as ready
Overgrowth v0.30 DIS3L2 Zornitza Stark Gene: dis3l2 has been classified as Green List (High Evidence).
Overgrowth v0.30 DIS3L2 Zornitza Stark Phenotypes for gene: DIS3L2 were changed from to Perlman syndrome, MIM# 267000
Overgrowth v0.29 DIS3L2 Zornitza Stark Publications for gene: DIS3L2 were set to
Overgrowth v0.28 DIS3L2 Zornitza Stark Mode of inheritance for gene: DIS3L2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Overgrowth v0.27 DIS3L2 Zornitza Stark reviewed gene: DIS3L2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22306653, 28328139, 29950491; Phenotypes: Perlman syndrome, MIM# 267000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Overgrowth v0.27 AKT2 Zornitza Stark Marked gene: AKT2 as ready
Overgrowth v0.27 AKT2 Zornitza Stark Gene: akt2 has been classified as Green List (High Evidence).
Overgrowth v0.27 AKT2 Zornitza Stark Classified gene: AKT2 as Green List (high evidence)
Overgrowth v0.27 AKT2 Zornitza Stark Gene: akt2 has been classified as Green List (High Evidence).
Overgrowth v0.26 AKT2 Zornitza Stark gene: AKT2 was added
gene: AKT2 was added to Overgrowth. Sources: Expert list
Mode of inheritance for gene: AKT2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AKT2 were set to 21979934
Phenotypes for gene: AKT2 were set to Hypoinsulinemic hypoglycemia with hemihypertrophy, MIM# 240900
Mode of pathogenicity for gene: AKT2 was set to Other
Review for gene: AKT2 was set to GREEN
Added comment: Three unrelated individuals reported with same de novo recurring missense variant, postulated to be activating, E17K.
Sources: Expert list
Overgrowth v0.25 ABCC9 Zornitza Stark Marked gene: ABCC9 as ready
Overgrowth v0.25 ABCC9 Zornitza Stark Gene: abcc9 has been classified as Green List (High Evidence).
Overgrowth v0.25 ABCC9 Zornitza Stark Phenotypes for gene: ABCC9 were changed from to Hypertrichotic osteochondrodysplasia, MIM# 239850; Cantu syndrome
Overgrowth v0.24 ABCC9 Zornitza Stark Publications for gene: ABCC9 were set to
Overgrowth v0.23 ABCC9 Zornitza Stark Mode of inheritance for gene: ABCC9 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Overgrowth v0.22 ABCC9 Zornitza Stark reviewed gene: ABCC9: Rating: GREEN; Mode of pathogenicity: None; Publications: 22610116, 22608503; Phenotypes: Hypertrichotic osteochondrodysplasia, MIM# 239850, Cantu syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rasopathy v0.31 PTPN11 Zornitza Stark Phenotypes for gene: PTPN11 were changed from LEOPARD syndrome 1, 151100 AD (for reporting use Noonan syndrome with multiple lentigines); Metachondromatosis, 156250 AD; Noonan syndrome 1, 163950 AD; Leukemia, juvenile myelomonocytic, somatic, 607785 to LEOPARD syndrome 1, 151100 AD (for reporting use Noonan syndrome with multiple lentigines); Noonan syndrome 1, 163950 AD
Mendeliome v0.3223 MRAS Zornitza Stark Marked gene: MRAS as ready
Mendeliome v0.3223 MRAS Zornitza Stark Gene: mras has been classified as Green List (High Evidence).
Mendeliome v0.3223 MRAS Zornitza Stark Classified gene: MRAS as Green List (high evidence)
Mendeliome v0.3223 MRAS Zornitza Stark Gene: mras has been classified as Green List (High Evidence).
Rasopathy v0.30 MRAS Zornitza Stark Classified gene: MRAS as Green List (high evidence)
Rasopathy v0.30 MRAS Zornitza Stark Gene: mras has been classified as Green List (High Evidence).
Mendeliome v0.3222 MRAS Zornitza Stark changed review comment from: Two unrelated individuals reported with de novo variants in this gene. Rated as LIMITED by ClinGen.
Sources: Expert list; to: Two unrelated individuals reported with de novo variants in this gene initially. Rated as LIMITED by ClinGen in 2018. Note 4 further individuals reported since.
Sources: Expert list
Mendeliome v0.3222 MRAS Zornitza Stark edited their review of gene: MRAS: Changed rating: GREEN; Changed publications: 28289718, 31173466, 31108500, 31173466
Rasopathy v0.29 MRAS Zornitza Stark changed review comment from: Two unrelated individuals reported with de novo variants in this gene. Rated as LIMITED by ClinGen.
Sources: Expert list; to: Two unrelated individuals reported with de novo variants in this gene. Rated as LIMITED by ClinGen in 2018. Note 4 further individuals reported since.
Sources: Expert list
Rasopathy v0.29 MRAS Zornitza Stark edited their review of gene: MRAS: Changed publications: 28289718, 31173466, 31108500, 31173466
Rasopathy v0.29 MRAS Zornitza Stark edited their review of gene: MRAS: Changed rating: GREEN; Changed publications: 28289718, 31173466, 31108500
Mendeliome v0.3222 MRAS Zornitza Stark gene: MRAS was added
gene: MRAS was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: MRAS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MRAS were set to 28289718
Phenotypes for gene: MRAS were set to Noonan syndrome
Review for gene: MRAS was set to AMBER
Added comment: Two unrelated individuals reported with de novo variants in this gene. Rated as LIMITED by ClinGen.
Sources: Expert list
Rasopathy v0.28 MRAS Zornitza Stark Marked gene: MRAS as ready
Rasopathy v0.28 MRAS Zornitza Stark Gene: mras has been classified as Amber List (Moderate Evidence).
Rasopathy v0.28 MRAS Zornitza Stark Classified gene: MRAS as Amber List (moderate evidence)
Rasopathy v0.28 MRAS Zornitza Stark Gene: mras has been classified as Amber List (Moderate Evidence).
Rasopathy v0.27 MRAS Zornitza Stark gene: MRAS was added
gene: MRAS was added to Rasopathy. Sources: Expert list
Mode of inheritance for gene: MRAS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MRAS were set to 28289718
Phenotypes for gene: MRAS were set to Noonan syndrome
Review for gene: MRAS was set to AMBER
Added comment: Two unrelated individuals reported with de novo variants in this gene. Rated as LIMITED by ClinGen.
Sources: Expert list
Rasopathy v0.26 RRAS Zornitza Stark Marked gene: RRAS as ready
Rasopathy v0.26 RRAS Zornitza Stark Gene: rras has been classified as Amber List (Moderate Evidence).
Rasopathy v0.26 RRAS Zornitza Stark Phenotypes for gene: RRAS were changed from to Noonan syndrome
Rasopathy v0.25 RRAS Zornitza Stark Publications for gene: RRAS were set to
Rasopathy v0.24 RRAS Zornitza Stark Mode of inheritance for gene: RRAS was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rasopathy v0.23 RRAS Zornitza Stark Classified gene: RRAS as Amber List (moderate evidence)
Rasopathy v0.23 RRAS Zornitza Stark Gene: rras has been classified as Amber List (Moderate Evidence).
Rasopathy v0.22 RRAS Zornitza Stark reviewed gene: RRAS: Rating: AMBER; Mode of pathogenicity: None; Publications: 24705357; Phenotypes: Noonan syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rasopathy v0.22 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Rare Disease
Mendeliome v0.3221 A2ML1 Zornitza Stark Marked gene: A2ML1 as ready
Mendeliome v0.3221 A2ML1 Zornitza Stark Gene: a2ml1 has been classified as Red List (Low Evidence).
Mendeliome v0.3221 A2ML1 Zornitza Stark Phenotypes for gene: A2ML1 were changed from to Noonan syndrome
Mendeliome v0.3220 A2ML1 Zornitza Stark Publications for gene: A2ML1 were set to
Mendeliome v0.3219 A2ML1 Zornitza Stark Mode of inheritance for gene: A2ML1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3218 A2ML1 Zornitza Stark Classified gene: A2ML1 as Red List (low evidence)
Mendeliome v0.3218 A2ML1 Zornitza Stark Gene: a2ml1 has been classified as Red List (Low Evidence).
Mendeliome v0.3217 A2ML1 Zornitza Stark reviewed gene: A2ML1: Rating: RED; Mode of pathogenicity: None; Publications: 24939586, 25862627; Phenotypes: Noonan syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Macrocephaly_Megalencephaly v0.41 A2ML1 Zornitza Stark Marked gene: A2ML1 as ready
Macrocephaly_Megalencephaly v0.41 A2ML1 Zornitza Stark Gene: a2ml1 has been classified as Red List (Low Evidence).
Macrocephaly_Megalencephaly v0.41 A2ML1 Zornitza Stark Phenotypes for gene: A2ML1 were changed from to Noonan syndrome
Macrocephaly_Megalencephaly v0.40 A2ML1 Zornitza Stark Publications for gene: A2ML1 were set to
Macrocephaly_Megalencephaly v0.39 A2ML1 Zornitza Stark Mode of inheritance for gene: A2ML1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Macrocephaly_Megalencephaly v0.38 A2ML1 Zornitza Stark Classified gene: A2ML1 as Red List (low evidence)
Macrocephaly_Megalencephaly v0.38 A2ML1 Zornitza Stark Gene: a2ml1 has been classified as Red List (Low Evidence).
Macrocephaly_Megalencephaly v0.37 A2ML1 Zornitza Stark Classified gene: A2ML1 as Red List (low evidence)
Macrocephaly_Megalencephaly v0.37 A2ML1 Zornitza Stark Gene: a2ml1 has been classified as Red List (Low Evidence).
Macrocephaly_Megalencephaly v0.37 A2ML1 Zornitza Stark Classified gene: A2ML1 as Red List (low evidence)
Macrocephaly_Megalencephaly v0.37 A2ML1 Zornitza Stark Gene: a2ml1 has been classified as Red List (Low Evidence).
Macrocephaly_Megalencephaly v0.36 A2ML1 Zornitza Stark reviewed gene: A2ML1: Rating: RED; Mode of pathogenicity: None; Publications: 24939586, 25862627; Phenotypes: Noonan syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rasopathy v0.21 A2ML1 Zornitza Stark Marked gene: A2ML1 as ready
Rasopathy v0.21 A2ML1 Zornitza Stark Gene: a2ml1 has been classified as Red List (Low Evidence).
Rasopathy v0.21 A2ML1 Zornitza Stark Phenotypes for gene: A2ML1 were changed from to Noonan syndrome
Rasopathy v0.20 A2ML1 Zornitza Stark Publications for gene: A2ML1 were set to
Rasopathy v0.19 A2ML1 Zornitza Stark edited their review of gene: A2ML1: Changed publications: 24939586, 25862627
Rasopathy v0.19 A2ML1 Zornitza Stark edited their review of gene: A2ML1: Changed publications: 24939586
Rasopathy v0.19 A2ML1 Zornitza Stark Classified gene: A2ML1 as Red List (low evidence)
Rasopathy v0.19 A2ML1 Zornitza Stark Gene: a2ml1 has been classified as Red List (Low Evidence).
Rasopathy v0.18 A2ML1 Zornitza Stark Tag disputed tag was added to gene: A2ML1.
Rasopathy v0.18 A2ML1 Zornitza Stark edited their review of gene: A2ML1: Changed rating: RED
Rasopathy v0.18 A2ML1 Zornitza Stark changed review comment from: Three unrelated individuals reported with de novo missense variants in this gene, zebrafish model.; to: Four unrelated individuals reported with de novo missense variants in this gene, zebrafish model. However, p.Arg802His is present in 168 heterozygotes in gnomad and one homozygote; p.Arg802Leu is also present in 168 heterozygotes, 1 homozygote; and p.Arg592Leu is present in 105 heterozygotes. Rated as DISPUTED by ClinGen.
Rasopathy v0.18 A2ML1 Zornitza Stark edited their review of gene: A2ML1: Changed rating: AMBER; Changed publications: 25862627
Rasopathy v0.18 A2ML1 Zornitza Stark Mode of inheritance for gene: A2ML1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rasopathy v0.17 A2ML1 Zornitza Stark reviewed gene: A2ML1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24939586; Phenotypes: Noonan syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v0.130 ACTB Zornitza Stark Marked gene: ACTB as ready
Craniosynostosis v0.130 ACTB Zornitza Stark Gene: actb has been classified as Green List (High Evidence).
Craniosynostosis v0.130 ACTB Zornitza Stark Phenotypes for gene: ACTB were changed from to Baraitser-Winter syndrome 1, MIM# 243310
Craniosynostosis v0.129 ACTB Zornitza Stark Mode of inheritance for gene: ACTB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v0.128 ACTG1 Zornitza Stark Marked gene: ACTG1 as ready
Craniosynostosis v0.128 ACTG1 Zornitza Stark Gene: actg1 has been classified as Green List (High Evidence).
Craniosynostosis v0.128 ACTG1 Zornitza Stark Phenotypes for gene: ACTG1 were changed from to Baraitser-Winter syndrome 2, MIM# 614583
Craniosynostosis v0.127 ACTG1 Zornitza Stark Mode of inheritance for gene: ACTG1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v0.126 MASP1 Zornitza Stark Marked gene: MASP1 as ready
Craniosynostosis v0.126 MASP1 Zornitza Stark Gene: masp1 has been classified as Green List (High Evidence).
Craniosynostosis v0.126 SKI Zornitza Stark Marked gene: SKI as ready
Craniosynostosis v0.126 SKI Zornitza Stark Gene: ski has been classified as Green List (High Evidence).
Craniosynostosis v0.126 TLK2 Zornitza Stark Marked gene: TLK2 as ready
Craniosynostosis v0.126 TLK2 Zornitza Stark Gene: tlk2 has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.126 TLK2 Zornitza Stark Phenotypes for gene: TLK2 were changed from to Mental retardation, autosomal dominant 57, MIM#618050
Craniosynostosis v0.125 TLK2 Zornitza Stark Publications for gene: TLK2 were set to
Craniosynostosis v0.124 TLK2 Zornitza Stark Mode of inheritance for gene: TLK2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v0.123 TLK2 Zornitza Stark Classified gene: TLK2 as Amber List (moderate evidence)
Craniosynostosis v0.123 TLK2 Zornitza Stark Gene: tlk2 has been classified as Amber List (Moderate Evidence).
Gastrointestinal neuromuscular disease v0.25 TMEM70 Bryony Thompson edited their review of gene: TMEM70: Changed rating: AMBER
Gastrointestinal neuromuscular disease v0.25 TMEM70 Bryony Thompson gene: TMEM70 was added
gene: TMEM70 was added to Gastrointestinal neuromuscular disease. Sources: NHS GMS
Mode of inheritance for gene: TMEM70 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM70 were set to 21147908
Phenotypes for gene: TMEM70 were set to Mitochondrial complex V (ATP synthase) deficiency, nuclear type 2 MIM#614052
Review for gene: TMEM70 was set to RED
Added comment: Intestinal pseudo-obstruction reported in one case and delayed gastric emptying reported in another case. Gastrointestinal neuromuscular disease does not appear to be a prominent feature of the condition.
Sources: NHS GMS
Gastrointestinal neuromuscular disease v0.24 ATRX Bryony Thompson Marked gene: ATRX as ready
Gastrointestinal neuromuscular disease v0.24 ATRX Bryony Thompson Gene: atrx has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v0.24 ATRX Bryony Thompson Classified gene: ATRX as Green List (high evidence)
Gastrointestinal neuromuscular disease v0.24 ATRX Bryony Thompson Gene: atrx has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v0.23 ATRX Bryony Thompson gene: ATRX was added
gene: ATRX was added to Gastrointestinal neuromuscular disease. Sources: NHS GMS
Mode of inheritance for gene: ATRX 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: ATRX were set to 16688741
Phenotypes for gene: ATRX were set to Alpha-thalassemia/mental retardation syndrome MIM#301040
Review for gene: ATRX was set to GREEN
Added comment: Gastrointestinal problems can be a prominent feature of the condition.
Sources: NHS GMS
Gastrointestinal neuromuscular disease v0.22 LMOD1 Bryony Thompson Marked gene: LMOD1 as ready
Gastrointestinal neuromuscular disease v0.22 LMOD1 Bryony Thompson Gene: lmod1 has been classified as Amber List (Moderate Evidence).
Gastrointestinal neuromuscular disease v0.22 LMOD1 Bryony Thompson reviewed gene: LMOD1: Rating: AMBER; Mode of pathogenicity: None; Publications: 28292896; Phenotypes: Megacystis microcolon intestinal hypoperistalsis syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Gastrointestinal neuromuscular disease v0.22 MYL9 Bryony Thompson Marked gene: MYL9 as ready
Gastrointestinal neuromuscular disease v0.22 MYL9 Bryony Thompson Gene: myl9 has been classified as Red List (Low Evidence).
Gastrointestinal neuromuscular disease v0.22 MYL9 Bryony Thompson gene: MYL9 was added
gene: MYL9 was added to Gastrointestinal neuromuscular disease. Sources: Literature
Mode of inheritance for gene: MYL9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYL9 were set to 29453416
Phenotypes for gene: MYL9 were set to Megacystis-microcolon-intestinal hypoperistalsis syndrome
Review for gene: MYL9 was set to RED
Added comment: Single consanguineous family reported with a homozygous deletion including the last exon of the gene. No functional evidence.
Sources: Literature
Craniosynostosis v0.121 TMCO1 Zornitza Stark Marked gene: TMCO1 as ready
Craniosynostosis v0.121 TMCO1 Zornitza Stark Gene: tmco1 has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.121 TMCO1 Zornitza Stark Classified gene: TMCO1 as Amber List (moderate evidence)
Craniosynostosis v0.121 TMCO1 Zornitza Stark Gene: tmco1 has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.120 TMCO1 Zornitza Stark gene: TMCO1 was added
gene: TMCO1 was added to Craniosynostosis. Sources: Expert list
Mode of inheritance for gene: TMCO1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMCO1 were set to 20018682; 24424126; 24194475
Phenotypes for gene: TMCO1 were set to Craniofacial dysmorphism, skeletal anomalies, and mental retardation syndrome, MIM# 213980
Review for gene: TMCO1 was set to AMBER
Added comment: Craniosynostosis reported in a small number of affected individuals, also note founder mutation in Amish.
Sources: Expert list
Craniosynostosis v0.119 TFAP2B Zornitza Stark Marked gene: TFAP2B as ready
Craniosynostosis v0.119 TFAP2B Zornitza Stark Gene: tfap2b has been classified as Green List (High Evidence).
Craniosynostosis v0.119 TFAP2B Zornitza Stark Classified gene: TFAP2B as Green List (high evidence)
Craniosynostosis v0.119 TFAP2B Zornitza Stark Gene: tfap2b has been classified as Green List (High Evidence).
Craniosynostosis v0.118 TFAP2B Zornitza Stark gene: TFAP2B was added
gene: TFAP2B was added to Craniosynostosis. Sources: Expert list
Mode of inheritance for gene: TFAP2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TFAP2B were set to 31292255
Phenotypes for gene: TFAP2B were set to Syndromic craniosynostosis
Review for gene: TFAP2B was set to GREEN
Added comment: Four individuals reported in PMID: 31292255 (Correction in PMID: 31405973) as part of a craniosynostosis cohort: 2 de novo and 2 inherited. There is evidence for reduced penetrance as in one case the variant was inherited from an unaffected parent (affected parent for the other inherited variant).
Sources: Expert list
Gastrointestinal neuromuscular disease v0.21 RET Bryony Thompson Classified gene: RET as Green List (high evidence)
Gastrointestinal neuromuscular disease v0.21 RET Bryony Thompson Gene: ret has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v0.20 SEMA3D Bryony Thompson Marked gene: SEMA3D as ready
Gastrointestinal neuromuscular disease v0.20 SEMA3D Bryony Thompson Gene: sema3d has been classified as Red List (Low Evidence).
Gastrointestinal neuromuscular disease v0.20 SEMA3D Bryony Thompson gene: SEMA3D was added
gene: SEMA3D was added to Gastrointestinal neuromuscular disease. Sources: Expert list
Mode of inheritance for gene: SEMA3D was set to Unknown
Publications for gene: SEMA3D were set to 28334784; 25839327
Phenotypes for gene: SEMA3D were set to Hirschsprung disease
Review for gene: SEMA3D was set to RED
Added comment: Reported as a common susceptibility loci. No reported evidence for an association with Mendelian disease. Sema3d null heterozygote and homozygote mouse model had normal intestinal innervation.
Sources: Expert list
Gastrointestinal neuromuscular disease v0.19 SEMA3C Bryony Thompson edited their review of gene: SEMA3C: Changed publications: 25839327, 31240788
Gastrointestinal neuromuscular disease v0.19 SEMA3C Bryony Thompson Marked gene: SEMA3C as ready
Gastrointestinal neuromuscular disease v0.19 SEMA3C Bryony Thompson Gene: sema3c has been classified as Red List (Low Evidence).
Gastrointestinal neuromuscular disease v0.19 SEMA3C Bryony Thompson gene: SEMA3C was added
gene: SEMA3C was added to Gastrointestinal neuromuscular disease. Sources: Expert list
Mode of inheritance for gene: SEMA3C was set to Unknown
Publications for gene: SEMA3C were set to 25839327
Phenotypes for gene: SEMA3C were set to Hirschsprung disease
Review for gene: SEMA3C was set to RED
Added comment: Common susceptibility loci for Hirschsprung disease. No reported evidence that it is associated with Mendelian disease.
Sources: Expert list
Gastrointestinal neuromuscular disease v0.18 NRG3 Bryony Thompson Marked gene: NRG3 as ready
Gastrointestinal neuromuscular disease v0.18 NRG3 Bryony Thompson Gene: nrg3 has been classified as Red List (Low Evidence).
Gastrointestinal neuromuscular disease v0.18 NRG3 Bryony Thompson gene: NRG3 was added
gene: NRG3 was added to Gastrointestinal neuromuscular disease. Sources: Expert list
Mode of inheritance for gene: NRG3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NRG3 were set to 23315268
Phenotypes for gene: NRG3 were set to Hirschsprung disease
Review for gene: NRG3 was set to RED
Added comment: Single Chinese mother and son reported, and some sporadic cases that appear to have recurrent variants that may be polymorphisms. No functional evidence.
Sources: Expert list
Mendeliome v0.3217 NRG1 Bryony Thompson Marked gene: NRG1 as ready
Mendeliome v0.3217 NRG1 Bryony Thompson Gene: nrg1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3217 NRG1 Bryony Thompson Classified gene: NRG1 as Amber List (moderate evidence)
Mendeliome v0.3217 NRG1 Bryony Thompson Gene: nrg1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3216 NRG1 Bryony Thompson gene: NRG1 was added
gene: NRG1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: NRG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NRG1 were set to 22574178; 21706185; 28190554
Phenotypes for gene: NRG1 were set to Hirschsprung disease
Review for gene: NRG1 was set to AMBER
Added comment: Has been reported as a Hirschsprung disease susceptibility loci, with common, low-penetrance polymorphisms that contribute only partially to risk and can act as genetic modifiers. There are also two publications with rare variants reported in this gene (at least one de novo) and supporting in vitro functional assays. A null zebrafish model was also supportive of a role in Hirschsprung disease.
Sources: Expert list
Gastrointestinal neuromuscular disease v0.17 NRG1 Bryony Thompson changed review comment from: Has been reported as a Hirschsprung disease susceptibility loci, with common, low-penetrance polymorphisms that contribute only partially to risk and can act as genetic modifiers. There are also two publications with rare variants reported in this gene and supporting in vitro functional assays. A null zebrafish model was also supportive of a role in Hirschsprung disease.
Sources: Expert list; to: Has been reported as a Hirschsprung disease susceptibility loci, with common, low-penetrance polymorphisms that contribute only partially to risk and can act as genetic modifiers. There are also two publications with rare variants reported in this gene (at least one de novo) and supporting in vitro functional assays. A null zebrafish model was also supportive of a role in Hirschsprung disease.
Sources: Expert list
Gastrointestinal neuromuscular disease v0.17 NRG1 Bryony Thompson Marked gene: NRG1 as ready
Gastrointestinal neuromuscular disease v0.17 NRG1 Bryony Thompson Gene: nrg1 has been classified as Amber List (Moderate Evidence).
Gastrointestinal neuromuscular disease v0.17 NRG1 Bryony Thompson Classified gene: NRG1 as Amber List (moderate evidence)
Gastrointestinal neuromuscular disease v0.17 NRG1 Bryony Thompson Gene: nrg1 has been classified as Amber List (Moderate Evidence).
Gastrointestinal neuromuscular disease v0.16 NRG1 Bryony Thompson gene: NRG1 was added
gene: NRG1 was added to Gastrointestinal neuromuscular disease. Sources: Expert list
Mode of inheritance for gene: NRG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NRG1 were set to 22574178; 21706185; 28190554
Phenotypes for gene: NRG1 were set to Hirschsprung disease
Review for gene: NRG1 was set to AMBER
Added comment: Has been reported as a Hirschsprung disease susceptibility loci, with common, low-penetrance polymorphisms that contribute only partially to risk and can act as genetic modifiers. There are also two publications with rare variants reported in this gene and supporting in vitro functional assays. A null zebrafish model was also supportive of a role in Hirschsprung disease.
Sources: Expert list
Craniosynostosis v0.117 STAT3 Zornitza Stark Marked gene: STAT3 as ready
Craniosynostosis v0.117 STAT3 Zornitza Stark Gene: stat3 has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.117 STAT3 Zornitza Stark Classified gene: STAT3 as Amber List (moderate evidence)
Craniosynostosis v0.117 STAT3 Zornitza Stark Gene: stat3 has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.116 STAT3 Zornitza Stark gene: STAT3 was added
gene: STAT3 was added to Craniosynostosis. Sources: Expert list
Mode of inheritance for gene: STAT3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: STAT3 were set to 20159255
Phenotypes for gene: STAT3 were set to Hyper-IgE recurrent infection syndrome, MIM# 147060
Review for gene: STAT3 was set to AMBER
Added comment: Craniosynostosis is a rarely described feature of this condition.
Sources: Expert list
Craniosynostosis v0.115 SPECC1L Zornitza Stark Phenotypes for gene: SPECC1L were changed from Hypertelorism, Teebi type MIM#145420 to Hypertelorism, Teebi type MIM#145420; Opitz GBBB syndrome, type II, MIM#145410
Craniosynostosis v0.114 SPECC1L Zornitza Stark Publications for gene: SPECC1L were set to 26111080; 30472488
Gastrointestinal neuromuscular disease v0.15 ECE1 Bryony Thompson Marked gene: ECE1 as ready
Gastrointestinal neuromuscular disease v0.15 ECE1 Bryony Thompson Gene: ece1 has been classified as Red List (Low Evidence).
Gastrointestinal neuromuscular disease v0.15 ECE1 Bryony Thompson gene: ECE1 was added
gene: ECE1 was added to Gastrointestinal neuromuscular disease. Sources: Expert list
Mode of inheritance for gene: ECE1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ECE1 were set to 9915973
Phenotypes for gene: ECE1 were set to ?Hirschsprung disease, cardiac defects, and autonomic dysfunction MIM#613870
Review for gene: ECE1 was set to RED
Added comment: A single case reported with Arg742Cys. Although this variant causes a loss of function in in vitro assays the NFE AF is higher than expected for a dominant disorder (0.0004, 50/127,302 alleles).
Sources: Expert list
Deafness_IsolatedAndComplex v0.358 FOXI1 Lilian Downie commented on gene: FOXI1: Disputed evidence for enlarged vestibular aqueduct PMID: 19204907
Craniosynostosis v0.113 SPECC1L Zornitza Stark Classified gene: SPECC1L as Green List (high evidence)
Craniosynostosis v0.113 SPECC1L Zornitza Stark Gene: specc1l has been classified as Green List (High Evidence).
Craniosynostosis v0.112 SPECC1L Zornitza Stark reviewed gene: SPECC1L: Rating: GREEN; Mode of pathogenicity: None; Publications: 25412741; Phenotypes: Hypertelorism, Teebi type, MIM# 145420, Opitz GBBB syndrome, type II, MIM#145410; Mode of inheritance: None
Craniosynostosis v0.112 SMAD3 Zornitza Stark Phenotypes for gene: SMAD3 were changed from LOEYS-DIETZ SYNDROME to Loeys-Dietz syndrome 3, MIM# 613795
Craniosynostosis v0.111 SMAD3 Zornitza Stark Publications for gene: SMAD3 were set to 20301312
Craniosynostosis v0.110 SMAD3 Zornitza Stark reviewed gene: SMAD3: Rating: GREEN; Mode of pathogenicity: None; Publications: 29392890; Phenotypes: Loeys-Dietz syndrome 3, MIM# 613795; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v0.110 PHEX Zornitza Stark Marked gene: PHEX as ready
Craniosynostosis v0.110 PHEX Zornitza Stark Gene: phex has been classified as Green List (High Evidence).