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Pulmonary Fibrosis_Interstitial Lung Disease v0.15 MARS Zornitza Stark Marked gene: MARS as ready
Pulmonary Fibrosis_Interstitial Lung Disease v0.15 MARS Zornitza Stark Gene: mars has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.15 MARS Zornitza Stark Classified gene: MARS as Green List (high evidence)
Pulmonary Fibrosis_Interstitial Lung Disease v0.15 MARS Zornitza Stark Gene: mars has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.14 MARS Zornitza Stark gene: MARS was added
gene: MARS was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Expert list
Mode of inheritance for gene: MARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MARS were set to 24103465; 25913036
Phenotypes for gene: MARS were set to Interstitial lung and liver disease, MIM#615486
Review for gene: MARS was set to GREEN
Added comment: Autosomal recessive disorder characterized by onset of respiratory insufficiency and progressive liver disease in infancy or early childhood. More than 5 unrelated families reported. Founder variants in Reunion Island, p.Ser567Leu and p.Ala393Thr, in cis.

Pathologic examination of lung lavage is consistent with pulmonary alveolar proteinosis.
Sources: Expert list
Liver Failure_Paediatric v0.38 MARS Zornitza Stark Marked gene: MARS as ready
Liver Failure_Paediatric v0.38 MARS Zornitza Stark Gene: mars has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.38 MARS Zornitza Stark Classified gene: MARS as Green List (high evidence)
Liver Failure_Paediatric v0.38 MARS Zornitza Stark Gene: mars has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.37 MARS Zornitza Stark gene: MARS was added
gene: MARS was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: MARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MARS were set to 24103465; 25913036
Phenotypes for gene: MARS were set to Interstitial lung and liver disease, MIM#615486
Review for gene: MARS was set to GREEN
Added comment: Autosomal recessive disorder characterized by onset of respiratory insufficiency and progressive liver disease in infancy or early childhood.

More than 5 unrelated families reported. Founder variants in Reunion Island, p.Ser567Leu and p.Ala393Thr, in cis.
Sources: Expert list
Liver Failure_Paediatric v0.36 ATP7B Zornitza Stark Marked gene: ATP7B as ready
Liver Failure_Paediatric v0.36 ATP7B Zornitza Stark Gene: atp7b has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.36 ATP7B Zornitza Stark Classified gene: ATP7B as Green List (high evidence)
Liver Failure_Paediatric v0.36 ATP7B Zornitza Stark Gene: atp7b has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.35 ATP7B Zornitza Stark gene: ATP7B was added
gene: ATP7B was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: ATP7B was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ATP7B were set to Wilson disease, MIM#277900
Review for gene: ATP7B was set to GREEN
Added comment: Well established gene-disease association. Can present with liver failure in childhood.
Sources: Expert list
Regression v0.205 SLC30A10 Zornitza Stark Marked gene: SLC30A10 as ready
Regression v0.205 SLC30A10 Zornitza Stark Gene: slc30a10 has been classified as Green List (High Evidence).
Regression v0.205 SLC30A10 Zornitza Stark Phenotypes for gene: SLC30A10 were changed from to Hypermanganesemia with dystonia 1, MIM# 613280
Regression v0.204 SLC30A10 Zornitza Stark Publications for gene: SLC30A10 were set to
Regression v0.203 SLC30A10 Zornitza Stark Mode of inheritance for gene: SLC30A10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Regression v0.202 SLC30A10 Zornitza Stark reviewed gene: SLC30A10: Rating: GREEN; Mode of pathogenicity: None; Publications: 22341972, 22341971, 29193034; Phenotypes: Hypermanganesemia with dystonia 1, MIM# 613280; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5216 SLC30A10 Zornitza Stark Marked gene: SLC30A10 as ready
Mendeliome v0.5216 SLC30A10 Zornitza Stark Gene: slc30a10 has been classified as Green List (High Evidence).
Mendeliome v0.5216 SLC30A10 Zornitza Stark Phenotypes for gene: SLC30A10 were changed from to Hypermanganesemia with dystonia 1, MIM# 613280
Mendeliome v0.5215 SLC30A10 Zornitza Stark Publications for gene: SLC30A10 were set to
Mendeliome v0.5214 SLC30A10 Zornitza Stark Mode of inheritance for gene: SLC30A10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5213 SLC30A10 Zornitza Stark reviewed gene: SLC30A10: Rating: GREEN; Mode of pathogenicity: None; Publications: 22341972, 22341971, 29193034; Phenotypes: Hypermanganesemia with dystonia 1, MIM# 613280; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Liver Failure_Paediatric v0.34 SLC30A10 Zornitza Stark Marked gene: SLC30A10 as ready
Liver Failure_Paediatric v0.34 SLC30A10 Zornitza Stark Gene: slc30a10 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.34 SLC30A10 Zornitza Stark Classified gene: SLC30A10 as Green List (high evidence)
Liver Failure_Paediatric v0.34 SLC30A10 Zornitza Stark Gene: slc30a10 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.33 SLC30A10 Zornitza Stark changed review comment from: autosomal recessive metabolic disorder characterized by increased serum manganese, motor neurodegeneration with extrapyramidal features, polycythemia, and hepatic dysfunction, which leads to cirrhosis in some cases. Intellectual function is preserved.

More than 10 unrelated families reported.
Sources: Expert list; to: Autosomal recessive metabolic disorder characterized by increased serum manganese, motor neurodegeneration with extrapyramidal features, polycythemia, and hepatic dysfunction, which leads to cirrhosis in some cases. Intellectual function is preserved.

More than 10 unrelated families reported.
Sources: Expert list
Liver Failure_Paediatric v0.33 SLC30A10 Zornitza Stark gene: SLC30A10 was added
gene: SLC30A10 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: SLC30A10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC30A10 were set to 22341972; 22341971; 29193034
Phenotypes for gene: SLC30A10 were set to Hypermanganesemia with dystonia 1, MIM# 613280
Review for gene: SLC30A10 was set to GREEN
Added comment: autosomal recessive metabolic disorder characterized by increased serum manganese, motor neurodegeneration with extrapyramidal features, polycythemia, and hepatic dysfunction, which leads to cirrhosis in some cases. Intellectual function is preserved.

More than 10 unrelated families reported.
Sources: Expert list
Liver Failure_Paediatric v0.32 Zornitza Stark Panel name changed from Acute Liver Failure_Paediatric to Liver Failure_Paediatric
Cholestasis v0.180 SLC27A5 Zornitza Stark Phenotypes for gene: SLC27A5 were changed from to Disorder of bile acid metabolism
Cholestasis v0.179 SLC27A5 Zornitza Stark edited their review of gene: SLC27A5: Changed phenotypes: Disorder of bile acid metabolism
Liver Failure_Paediatric v0.31 MPI Zornitza Stark Marked gene: MPI as ready
Liver Failure_Paediatric v0.31 MPI Zornitza Stark Gene: mpi has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.31 MPI Zornitza Stark Classified gene: MPI as Green List (high evidence)
Liver Failure_Paediatric v0.31 MPI Zornitza Stark Gene: mpi has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.30 MPI Zornitza Stark gene: MPI was added
gene: MPI was added to Acute Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: MPI was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MPI were set to 25902754
Phenotypes for gene: MPI were set to Congenital disorder of glycosylation, type Ib, MIM# 602579
Review for gene: MPI was set to GREEN
Added comment: Hepatic involvement is prominent and liver failure reported.
Sources: Expert list
Liver Failure_Paediatric v0.29 LIPA Zornitza Stark Marked gene: LIPA as ready
Liver Failure_Paediatric v0.29 LIPA Zornitza Stark Gene: lipa has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.29 LIPA Zornitza Stark Classified gene: LIPA as Green List (high evidence)
Liver Failure_Paediatric v0.29 LIPA Zornitza Stark Gene: lipa has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.28 LIPA Zornitza Stark gene: LIPA was added
gene: LIPA was added to Acute Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: LIPA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LIPA were set to 8617513; 21963785
Phenotypes for gene: LIPA were set to Cholesteryl ester storage disease, MIM# 278000; Wolman disease, MIM# 278000
Review for gene: LIPA was set to GREEN
Added comment: Liver failure can be of early onset and rapidly progressive or more chronic.
Sources: Expert list
Liver Failure_Paediatric v0.27 NPC1 Zornitza Stark Marked gene: NPC1 as ready
Liver Failure_Paediatric v0.27 NPC1 Zornitza Stark Gene: npc1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.27 NPC1 Zornitza Stark Classified gene: NPC1 as Green List (high evidence)
Liver Failure_Paediatric v0.27 NPC1 Zornitza Stark Gene: npc1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.26 NPC1 Zornitza Stark gene: NPC1 was added
gene: NPC1 was added to Acute Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: NPC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NPC1 were set to 25902754
Phenotypes for gene: NPC1 were set to Niemann-Pick disease, MIM# 257220
Review for gene: NPC1 was set to GREEN
Added comment: Rare presentations with liver failure reported.
Sources: Expert list
Liver Failure_Paediatric v0.25 TRMU Zornitza Stark Marked gene: TRMU as ready
Liver Failure_Paediatric v0.25 TRMU Zornitza Stark Gene: trmu has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.25 TRMU Zornitza Stark Classified gene: TRMU as Green List (high evidence)
Liver Failure_Paediatric v0.25 TRMU Zornitza Stark Gene: trmu has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.24 TRMU Zornitza Stark gene: TRMU was added
gene: TRMU was added to Acute Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: TRMU was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRMU were set to 19732863
Phenotypes for gene: TRMU were set to Liver failure, transient infantile, MIM# 613070
Review for gene: TRMU was set to GREEN
Added comment: Acute infantile liver failure resulting from variants in TRMU is a transient disorder of hepatic function. In addition to elevated liver enzymes, jaundice, vomiting, coagulopathy, and hyperbilirubinemia, the presence of increased serum lactate is consistent with a defect in mitochondrial respiratory function. With supportive care, patients who survive the initial acute episode can recover and show normal development.

Thirteen individuals reported, including 7 of Yemenite Jewish origin with same recurrent founder variant, p.Tyr77His.
Sources: Expert list
Liver Failure_Paediatric v0.23 RINT1 Zornitza Stark Marked gene: RINT1 as ready
Liver Failure_Paediatric v0.23 RINT1 Zornitza Stark Gene: rint1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.23 RINT1 Zornitza Stark Classified gene: RINT1 as Green List (high evidence)
Liver Failure_Paediatric v0.23 RINT1 Zornitza Stark Gene: rint1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.22 RINT1 Zornitza Stark gene: RINT1 was added
gene: RINT1 was added to Acute Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: RINT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RINT1 were set to 31204009
Phenotypes for gene: RINT1 were set to Infantile liver failure syndrome 3, MIM# 618641
Review for gene: RINT1 was set to GREEN
Added comment: Recurrent episodes of acute liver failure during intercurrent febrile illness. Patients first present in infancy or early childhood, and there usually is complete recovery between episodes with conservative treatment. Affected individuals also have skeletal anomalies of the vertebral bodies and femoral heads.

Three unrelated families reported.
Sources: Expert list
Liver Failure_Paediatric v0.21 LARS Zornitza Stark Marked gene: LARS as ready
Liver Failure_Paediatric v0.21 LARS Zornitza Stark Gene: lars has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.21 LARS Zornitza Stark Classified gene: LARS as Green List (high evidence)
Liver Failure_Paediatric v0.21 LARS Zornitza Stark Gene: lars has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.20 LARS Zornitza Stark gene: LARS was added
gene: LARS was added to Acute Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: LARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LARS were set to 30349989
Phenotypes for gene: LARS were set to Infantile liver failure syndrome 1, MIM# 615438
Review for gene: LARS was set to GREEN
Added comment: Six unrelated families reported in the literature, reviewed in PMID: 30349989.
Sources: Expert list
Liver Failure_Paediatric v0.19 NBAS Zornitza Stark Marked gene: NBAS as ready
Liver Failure_Paediatric v0.19 NBAS Zornitza Stark Gene: nbas has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.19 NBAS Zornitza Stark Classified gene: NBAS as Green List (high evidence)
Liver Failure_Paediatric v0.19 NBAS Zornitza Stark Gene: nbas has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.18 NBAS Zornitza Stark gene: NBAS was added
gene: NBAS was added to Acute Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: NBAS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NBAS were set to 26073778
Phenotypes for gene: NBAS were set to Infantile liver failure syndrome 2, MIM# 616483
Review for gene: NBAS was set to GREEN
Added comment: Recurrent episodes of acute liver failure during intercurrent febrile illness. More than 10 unrelated families reported.
Sources: Expert list
Liver Failure_Paediatric v0.17 OTC Zornitza Stark Marked gene: OTC as ready
Liver Failure_Paediatric v0.17 OTC Zornitza Stark Gene: otc has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.17 OTC Zornitza Stark Classified gene: OTC as Green List (high evidence)
Liver Failure_Paediatric v0.17 OTC Zornitza Stark Gene: otc has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.16 OTC Zornitza Stark gene: OTC was added
gene: OTC was added to Acute Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: OTC 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: OTC were set to 28887792; 25902754
Phenotypes for gene: OTC were set to Ornithine transcarbamylase deficiency, MIM# 311250
Review for gene: OTC was set to GREEN
Added comment: Well established gene disease association.

Reports of presentations with liver failure.
Sources: Expert list
Liver Failure_Paediatric v0.15 MPV17 Zornitza Stark Marked gene: MPV17 as ready
Liver Failure_Paediatric v0.15 MPV17 Zornitza Stark Gene: mpv17 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.15 MPV17 Zornitza Stark Classified gene: MPV17 as Green List (high evidence)
Liver Failure_Paediatric v0.15 MPV17 Zornitza Stark Gene: mpv17 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.14 MPV17 Zornitza Stark gene: MPV17 was added
gene: MPV17 was added to Acute Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: MPV17 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MPV17 were set to 18695062
Phenotypes for gene: MPV17 were set to Mitochondrial DNA depletion syndrome 6 (hepatocerebral type), MIM# 256810
Review for gene: MPV17 was set to GREEN
Added comment: Well established gene-disease association.

Mitochondrial DNA depletion syndrome-6 is an autosomal recessive disorder characterized by infantile onset of progressive liver failure, often leading to death in the first year of life. Those that survive develop progressive neurologic involvement, including ataxia, hypotonia, dystonia, and psychomotor regression.
Sources: Expert list
Liver Failure_Paediatric v0.13 DGUOK Zornitza Stark Marked gene: DGUOK as ready
Liver Failure_Paediatric v0.13 DGUOK Zornitza Stark Gene: dguok has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.13 DGUOK Zornitza Stark Classified gene: DGUOK as Green List (high evidence)
Liver Failure_Paediatric v0.13 DGUOK Zornitza Stark Gene: dguok has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.12 DGUOK Zornitza Stark Classified gene: DGUOK as Green List (high evidence)
Liver Failure_Paediatric v0.12 DGUOK Zornitza Stark Gene: dguok has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.11 DGUOK Zornitza Stark gene: DGUOK was added
gene: DGUOK was added to Acute Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: DGUOK was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DGUOK were set to Mitochondrial DNA depletion syndrome 3 (hepatocerebral type), MIM#251880
Review for gene: DGUOK was set to GREEN
Added comment: Well established gene-disease association.

Mitochondrial DNA depletion syndrome-3 is a severe autosomal recessive disorder characterized by onset in infancy of progressive liver failure and neurologic abnormalities, hypoglycemia, and increased lactate in body fluids. Affected tissues show both decreased activity of the mtDNA-encoded respiratory chain complexes (I, III, IV, and V) and mtDNA depletion.
Sources: Expert list
Liver Failure_Paediatric v0.10 POLG Zornitza Stark Marked gene: POLG as ready
Liver Failure_Paediatric v0.10 POLG Zornitza Stark Gene: polg has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.10 POLG Zornitza Stark Classified gene: POLG as Green List (high evidence)
Liver Failure_Paediatric v0.10 POLG Zornitza Stark Gene: polg has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.9 POLG Zornitza Stark gene: POLG was added
gene: POLG was added to Acute Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: POLG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLG were set to 20220442
Phenotypes for gene: POLG were set to Mitochondrial DNA depletion syndrome 4A (Alpers type), MIM# 203700
Review for gene: POLG was set to GREEN
Added comment: Well established gene-disease association.

Alpers syndrome is an autosomal recessive disorder characterized by a clinical triad of psychomotor retardation, intractable epilepsy, and liver failure in infants and young children. Pathologic findings include neuronal loss in the cerebral gray matter with reactive astrocytosis and liver cirrhosis. The disorder is progressive and often leads to death from hepatic failure or status epilepticus before age 3 years.
Sources: Expert list
Liver Failure_Paediatric v0.8 ACADM Zornitza Stark Marked gene: ACADM as ready
Liver Failure_Paediatric v0.8 ACADM Zornitza Stark Gene: acadm has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.8 ACADM Zornitza Stark Classified gene: ACADM as Green List (high evidence)
Liver Failure_Paediatric v0.8 ACADM Zornitza Stark Gene: acadm has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.7 ACADM Zornitza Stark gene: ACADM was added
gene: ACADM was added to Acute Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: ACADM was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ACADM were set to Acyl-CoA dehydrogenase, medium chain, deficiency of, MIM# 201450
Review for gene: ACADM was set to GREEN
Added comment: Inherited deficiency of medium-chain acyl-CoA dehydrogenase is characterized by intolerance to prolonged fasting, recurrent episodes of hypoglycemic coma with medium-chain dicarboxylic aciduria, impaired ketogenesis, and low plasma and tissue carnitine levels. Can progress to liver failure.
Sources: Expert list
Liver Failure_Paediatric v0.6 ALDOB Zornitza Stark Marked gene: ALDOB as ready
Liver Failure_Paediatric v0.6 ALDOB Zornitza Stark Gene: aldob has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.6 ALDOB Zornitza Stark Classified gene: ALDOB as Green List (high evidence)
Liver Failure_Paediatric v0.6 ALDOB Zornitza Stark Gene: aldob has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.5 ALDOB Zornitza Stark gene: ALDOB was added
gene: ALDOB was added to Acute Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: ALDOB was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ALDOB were set to Fructose intolerance, hereditary, MIM# 229600
Review for gene: ALDOB was set to GREEN
Added comment: Well established gene-disease association.

Hereditary fructose intolerance (HFI) becomes apparent in infancy at the time of weaning, when fructose or sucrose is added to the diet. Clinical features include recurrent vomiting, abdominal pain, and hypoglycemia that may be fatal. Long-term exposure to fructose can result in liver failure, renal tubulopathy, and growth retardation.
Sources: Expert list
Liver Failure_Paediatric v0.4 FAH Zornitza Stark Marked gene: FAH as ready
Liver Failure_Paediatric v0.4 FAH Zornitza Stark Gene: fah has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.4 FAH Zornitza Stark Classified gene: FAH as Green List (high evidence)
Liver Failure_Paediatric v0.4 FAH Zornitza Stark Gene: fah has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.3 FAH Zornitza Stark gene: FAH was added
gene: FAH was added to Acute Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: FAH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAH were set to 15759101
Phenotypes for gene: FAH were set to Tyrosinemia, type I, MIM#276700
Review for gene: FAH was set to GREEN
Added comment: Well established gene-disease association.

The disorder is characterized by progressive liver disease and a secondary renal tubular dysfunction leading to hypophosphatemic rickets. Onset varies from infancy to adolescence. In the most acute form patients present with severe liver failure within weeks after birth, whereas rickets may be the major symptom in chronic tyrosinemia. Untreated, death ensues from cirrhosis or hepatocellular carcinoma at a young age.
Sources: Expert list
Liver Failure_Paediatric v0.2 GALT Zornitza Stark Marked gene: GALT as ready
Liver Failure_Paediatric v0.2 GALT Zornitza Stark Gene: galt has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.2 GALT Zornitza Stark Classified gene: GALT as Green List (high evidence)
Liver Failure_Paediatric v0.2 GALT Zornitza Stark Gene: galt has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.1 GALT Zornitza Stark gene: GALT was added
gene: GALT was added to Acute Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: GALT was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GALT were set to Galactosaemia, MIM#230400
Review for gene: GALT was set to GREEN
Added comment: Well established gene-disease association. Most individuals present in the neonatal period, after ingestion of galactose, with jaundice, hepatosplenomegaly, hepatocellular insufficiency, food intolerance, hypoglycemia, renal tubular dysfunction, muscle hypotonia, sepsis, and cataract. Long-term complications include intellectual disability, verbal dyspraxia, motor abnormalities, and hypergonadotropic hypogonadism.

Commonly part of newborn screening program but currently not in Victoria.
Sources: Expert list
Liver Failure_Paediatric v0.0 Zornitza Stark Added Panel Acute Liver Failure_Paediatric
Set panel types to: Victorian Clinical Genetics Services; Rare Disease
Mendeliome v0.5213 DDX23 Bryony Thompson Classified gene: DDX23 as Amber List (moderate evidence)
Mendeliome v0.5213 DDX23 Bryony Thompson Gene: ddx23 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5212 DDX23 Bryony Thompson gene: DDX23 was added
gene: DDX23 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DDX23 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DDX23 were set to 33057194
Phenotypes for gene: DDX23 were set to Developmental disorder
Review for gene: DDX23 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio developmental disorder study. 6 de novo missense identified in ~10,000 cases with developmental disorders (no other phenotype info provided)
Sources: Literature
Mendeliome v0.5211 ATP6V0A1 Bryony Thompson Classified gene: ATP6V0A1 as Amber List (moderate evidence)
Mendeliome v0.5211 ATP6V0A1 Bryony Thompson Gene: atp6v0a1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5210 ATP6V0A1 Bryony Thompson gene: ATP6V0A1 was added
gene: ATP6V0A1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ATP6V0A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP6V0A1 were set to 30842224; 33057194
Phenotypes for gene: ATP6V0A1 were set to Developmental disorder; Rett syndrome-like
Review for gene: ATP6V0A1 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio developmental disorder study. 11 de novo missense identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
PMID: 30842224 - identified a de novo missense variant in a single individual with atypical Rett syndrome phenotype
Sources: Literature
Mendeliome v0.5209 ARHGAP35 Bryony Thompson Marked gene: ARHGAP35 as ready
Mendeliome v0.5209 ARHGAP35 Bryony Thompson Gene: arhgap35 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5209 ARHGAP35 Bryony Thompson Classified gene: ARHGAP35 as Amber List (moderate evidence)
Mendeliome v0.5209 ARHGAP35 Bryony Thompson Gene: arhgap35 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5208 ARHGAP35 Bryony Thompson gene: ARHGAP35 was added
gene: ARHGAP35 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ARHGAP35 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARHGAP35 were set to 33057194
Phenotypes for gene: ARHGAP35 were set to Developmental disorder
Review for gene: ARHGAP35 was set to AMBER
Added comment: Has been identified as a gene with significant de novo enrichment in a large trio developmental disorder study. 16 de novo variants (3 frameshift, 2 in-frame, 10 missense, 1 stopgain) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Sources: Literature
Mendeliome v0.5207 AP2S1 Bryony Thompson Added comment: Comment on phenotypes: Established hypercalcaemia gene.
PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio developmental disorder study. 5 de novo missense identified in ~10,000 cases with developmental disorders (no other phenotype info provided)
Mendeliome v0.5207 AP2S1 Bryony Thompson Phenotypes for gene: AP2S1 were changed from Hypocalciuric hypercalcemia, type III MIM#600740 to Hypocalciuric hypercalcemia, type III MIM#600740
Mendeliome v0.5206 AP2S1 Bryony Thompson Mode of inheritance for gene: AP2S1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5205 AP2S1 Bryony Thompson Phenotypes for gene: AP2S1 were changed from to Hypocalciuric hypercalcemia, type III MIM#600740
Central Hypoventilation v0.27 RET Zornitza Stark Marked gene: RET as ready
Central Hypoventilation v0.27 RET Zornitza Stark Gene: ret has been classified as Red List (Low Evidence).
Central Hypoventilation v0.27 RET Zornitza Stark Phenotypes for gene: RET were changed from to Central hypoventilation syndrome, congenital, MIM#209880
Central Hypoventilation v0.26 RET Zornitza Stark Publications for gene: RET were set to
Central Hypoventilation v0.25 RET Zornitza Stark Mode of inheritance for gene: RET was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Central Hypoventilation v0.24 RET Zornitza Stark Classified gene: RET as Red List (low evidence)
Central Hypoventilation v0.24 RET Zornitza Stark Gene: ret has been classified as Red List (Low Evidence).
Central Hypoventilation v0.23 RET Zornitza Stark reviewed gene: RET: Rating: RED; Mode of pathogenicity: None; Publications: 18438890, 16443855, 12566528, 12086152; Phenotypes: Central hypoventilation syndrome, congenital, MIM#209880; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Central Hypoventilation v0.23 GDNF Zornitza Stark Marked gene: GDNF as ready
Central Hypoventilation v0.23 GDNF Zornitza Stark Gene: gdnf has been classified as Red List (Low Evidence).
Central Hypoventilation v0.23 GDNF Zornitza Stark Phenotypes for gene: GDNF were changed from to Central hypoventilation syndrome, MIM# 209880
Central Hypoventilation v0.22 GDNF Zornitza Stark Mode of inheritance for gene: GDNF was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Central Hypoventilation v0.21 GDNF Zornitza Stark Classified gene: GDNF as Red List (low evidence)
Central Hypoventilation v0.21 GDNF Zornitza Stark Gene: gdnf has been classified as Red List (Low Evidence).
Central Hypoventilation v0.20 GDNF Zornitza Stark reviewed gene: GDNF: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Central hypoventilation syndrome, MIM# 209880; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Central Hypoventilation v0.20 PHOX2B Zornitza Stark Marked gene: PHOX2B as ready
Central Hypoventilation v0.20 PHOX2B Zornitza Stark Gene: phox2b has been classified as Green List (High Evidence).
Central Hypoventilation v0.20 PHOX2B Zornitza Stark Phenotypes for gene: PHOX2B were changed from to Central hypoventilation syndrome, congenital, with or without Hirschsprung disease, MIM# 209880
Central Hypoventilation v0.19 PHOX2B Zornitza Stark Publications for gene: PHOX2B were set to
Central Hypoventilation v0.18 PHOX2B Zornitza Stark Mode of inheritance for gene: PHOX2B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Central Hypoventilation v0.17 PHOX2B Zornitza Stark reviewed gene: PHOX2B: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301600; Phenotypes: Central hypoventilation syndrome, congenital, with or without Hirschsprung disease, MIM# 209880; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Central Hypoventilation v0.17 BDNF Zornitza Stark Phenotypes for gene: BDNF were changed from to Central hypoventilation syndrome, congenital, MIM#209880
Central Hypoventilation v0.16 BDNF Zornitza Stark Mode of inheritance for gene: BDNF was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Central Hypoventilation v0.15 BDNF Zornitza Stark Tag refuted tag was added to gene: BDNF.
Central Hypoventilation v0.14 EDN3 Zornitza Stark Marked gene: EDN3 as ready
Central Hypoventilation v0.14 EDN3 Zornitza Stark Gene: edn3 has been classified as Red List (Low Evidence).
Central Hypoventilation v0.14 EDN3 Zornitza Stark Phenotypes for gene: EDN3 were changed from to Central hypoventilation syndrome, congenital, MIM# 209880
Central Hypoventilation v0.13 EDN3 Zornitza Stark Publications for gene: EDN3 were set to
Central Hypoventilation v0.12 EDN3 Zornitza Stark Mode of inheritance for gene: EDN3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Central Hypoventilation v0.11 EDN3 Zornitza Stark Classified gene: EDN3 as Red List (low evidence)
Central Hypoventilation v0.11 EDN3 Zornitza Stark Gene: edn3 has been classified as Red List (Low Evidence).
Central Hypoventilation v0.10 EDN3 Zornitza Stark Tag disputed tag was added to gene: EDN3.
Central Hypoventilation v0.10 EDN3 Zornitza Stark reviewed gene: EDN3: Rating: RED; Mode of pathogenicity: None; Publications: 8696331; Phenotypes: Central hypoventilation syndrome, congenital, MIM# 209880; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5204 ASCL1 Zornitza Stark Marked gene: ASCL1 as ready
Mendeliome v0.5204 ASCL1 Zornitza Stark Gene: ascl1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5204 ASCL1 Zornitza Stark Phenotypes for gene: ASCL1 were changed from to Central hypoventilation syndrome, congenital, MIM# 209880
Mendeliome v0.5203 ASCL1 Zornitza Stark Publications for gene: ASCL1 were set to
Mendeliome v0.5202 ASCL1 Zornitza Stark Mode of inheritance for gene: ASCL1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5201 ASCL1 Zornitza Stark Classified gene: ASCL1 as Amber List (moderate evidence)
Mendeliome v0.5201 ASCL1 Zornitza Stark Gene: ascl1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5200 ASCL1 Zornitza Stark reviewed gene: ASCL1: Rating: AMBER; Mode of pathogenicity: None; Publications: 14532329; Phenotypes: Central hypoventilation syndrome, congenital, MIM# 209880; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Central Hypoventilation v0.10 ASCL1 Zornitza Stark Marked gene: ASCL1 as ready
Central Hypoventilation v0.10 ASCL1 Zornitza Stark Gene: ascl1 has been classified as Amber List (Moderate Evidence).
Central Hypoventilation v0.10 ASCL1 Zornitza Stark Phenotypes for gene: ASCL1 were changed from to Central hypoventilation syndrome, congenital, MIM# 209880
Central Hypoventilation v0.9 ASCL1 Zornitza Stark Publications for gene: ASCL1 were set to
Central Hypoventilation v0.8 ASCL1 Zornitza Stark Mode of inheritance for gene: ASCL1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Central Hypoventilation v0.7 ASCL1 Zornitza Stark Classified gene: ASCL1 as Amber List (moderate evidence)
Central Hypoventilation v0.7 ASCL1 Zornitza Stark Gene: ascl1 has been classified as Amber List (Moderate Evidence).
Central Hypoventilation v0.6 ASCL1 Zornitza Stark reviewed gene: ASCL1: Rating: AMBER; Mode of pathogenicity: None; Publications: 14532329; Phenotypes: Central hypoventilation syndrome, congenital, MIM# 209880; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Chronic granulomatous disease v0.12 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Mendeliome v0.5200 ODC1 Zornitza Stark Phenotypes for gene: ODC1 were changed from Intellectual disability; macrocephaly; dysmorphism to Neurodevelopmental disorder with alopecia and brain imaging abnormalities (NEDABIA), MIM#619075
Mendeliome v0.5199 ODC1 Zornitza Stark Publications for gene: ODC1 were set to 30475435
Intellectual disability syndromic and non-syndromic v0.3127 ODC1 Zornitza Stark Publications for gene: ODC1 were set to 30475435
Intellectual disability syndromic and non-syndromic v0.3126 ODC1 Zornitza Stark edited their review of gene: ODC1: Added comment: Fifth individual reported in PMID 30239107: de novo nonsense variant identified, molecular modeling suggested that due to lack of a C terminus in the mutant protein, antizyme binding does not induce ODC degradation, leading to accumulation of active protein.; Changed publications: 30475435, 30239107
Mendeliome v0.5198 ODC1 Zornitza Stark commented on gene: ODC1: Fifth individual reported in PMID 30239107: de novo nonsense variant identified, molecular modeling suggested that due to lack of a C terminus in the mutant protein, antizyme binding does not induce ODC degradation, leading to accumulation of active protein.
Mendeliome v0.5198 ODC1 Zornitza Stark changed review comment from: Four individuals with de novo GoF variants in this gene reported.
Sources: Literature; to: Four individuals with de novo GoF variants in this gene reported.
Sources: Literature
Mendeliome v0.5198 ODC1 Zornitza Stark edited their review of gene: ODC1: Changed publications: 30475435, 30239107
Mendeliome v0.5198 ODC1 Zornitza Stark edited their review of gene: ODC1: Changed phenotypes: Neurodevelopmental disorder with alopecia and brain imaging abnormalities (NEDABIA), MIM#619075
Intellectual disability syndromic and non-syndromic v0.3126 ODC1 Zornitza Stark Phenotypes for gene: ODC1 were changed from Intellectual disability; macrocephaly; dysmorphism to Neurodevelopmental disorder with alopecia and brain imaging abnormalities (NEDABIA), MIM#619075
Intellectual disability syndromic and non-syndromic v0.3125 ODC1 Zornitza Stark edited their review of gene: ODC1: Changed phenotypes: Neurodevelopmental disorder with alopecia and brain imaging abnormalities (NEDABIA), MIM#619075
Intellectual disability syndromic and non-syndromic v0.3125 ODC1 Zornitza Stark edited their review of gene: ODC1: Changed phenotypes: neurodevelopmental disorder with alopecia and brain imaging abnormalities (NEDABIA), MIM#619075
Mendeliome v0.5198 KDELR2 Zornitza Stark Marked gene: KDELR2 as ready
Mendeliome v0.5198 KDELR2 Zornitza Stark Gene: kdelr2 has been classified as Green List (High Evidence).
Mendeliome v0.5198 KDELR2 Zornitza Stark Classified gene: KDELR2 as Green List (high evidence)
Mendeliome v0.5198 KDELR2 Zornitza Stark Gene: kdelr2 has been classified as Green List (High Evidence).
Mendeliome v0.5197 KDELR2 Zornitza Stark gene: KDELR2 was added
gene: KDELR2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: KDELR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KDELR2 were set to 33053334
Phenotypes for gene: KDELR2 were set to Increased susceptibility to fractures; joint hypermobility; Scoliosis; Bowing of the legs; Bowing of the arms
Review for gene: KDELR2 was set to GREEN
Added comment: 4 families with osteogenesis imperfecta reported with functional studies.
Sources: Expert list
Osteogenesis Imperfecta and Osteoporosis v0.48 KDELR2 Zornitza Stark Marked gene: KDELR2 as ready
Osteogenesis Imperfecta and Osteoporosis v0.48 KDELR2 Zornitza Stark Gene: kdelr2 has been classified as Green List (High Evidence).
Osteogenesis Imperfecta and Osteoporosis v0.48 KDELR2 Zornitza Stark Classified gene: KDELR2 as Green List (high evidence)
Osteogenesis Imperfecta and Osteoporosis v0.48 KDELR2 Zornitza Stark Gene: kdelr2 has been classified as Green List (High Evidence).
Osteogenesis Imperfecta and Osteoporosis v0.47 KDELR2 Zornitza Stark gene: KDELR2 was added
gene: KDELR2 was added to Osteogenesis Imperfecta. Sources: Expert Review
Mode of inheritance for gene: KDELR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KDELR2 were set to 33053334
Phenotypes for gene: KDELR2 were set to Increased susceptibility to fractures; joint hypermobility; Scoliosis; Bowing of the legs; Bowing of the arms
Review for gene: KDELR2 was set to GREEN
Added comment: 4 families with osteogenesis imperfecta reported with functional studies.
Sources: Expert Review
Mendeliome v0.5196 SCN8A Zornitza Stark Marked gene: SCN8A as ready
Mendeliome v0.5196 SCN8A Zornitza Stark Gene: scn8a has been classified as Green List (High Evidence).
Mendeliome v0.5196 SCN8A Zornitza Stark Phenotypes for gene: SCN8A were changed from to Developmental and epileptic encephalopathy 13, MIM#614558, dominant and recessive; Myoclonus, familial, 2, MIM# 618364; paroxysmal kinesigenic dyskinesias; Cognitive impairment with or without cerebellar ataxia, MIM# 614306
Mendeliome v0.5195 SCN8A Zornitza Stark Publications for gene: SCN8A were set to
Mendeliome v0.5194 SCN8A Zornitza Stark Mode of pathogenicity for gene: SCN8A was changed from to Other
Mendeliome v0.5193 SCN8A Zornitza Stark Mode of inheritance for gene: SCN8A was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5192 SCN8A Zornitza Stark reviewed gene: SCN8A: Rating: GREEN; Mode of pathogenicity: Other; Publications: 31625145, 29726066, 27098556, 28702509, 16236810, 31904124, 31887642, 31675620; Phenotypes: Developmental and epileptic encephalopathy 13, MIM#614558, dominant and recessive, Myoclonus, familial, 2, MIM# 618364, paroxysmal kinesigenic dyskinesias, Cognitive impairment with or without cerebellar ataxia, MIM# 614306; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Differences of Sex Development v0.179 GATA4 Zornitza Stark Marked gene: GATA4 as ready
Differences of Sex Development v0.179 GATA4 Zornitza Stark Gene: gata4 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.179 GATA4 Zornitza Stark Phenotypes for gene: GATA4 were changed from to Testicular anomalies with or without congenital heart disease, MIM# 615542
Differences of Sex Development v0.178 GATA4 Zornitza Stark Publications for gene: GATA4 were set to
Differences of Sex Development v0.177 GATA4 Zornitza Stark Mode of inheritance for gene: GATA4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.176 GATA4 Zornitza Stark Classified gene: GATA4 as Amber List (moderate evidence)
Differences of Sex Development v0.176 GATA4 Zornitza Stark Gene: gata4 has been classified as Amber List (Moderate Evidence).
Incidentalome v0.48 RAD51D Zornitza Stark Marked gene: RAD51D as ready
Incidentalome v0.48 RAD51D Zornitza Stark Gene: rad51d has been classified as Green List (High Evidence).
Incidentalome v0.48 RAD51D Zornitza Stark Classified gene: RAD51D as Green List (high evidence)
Incidentalome v0.48 RAD51D Zornitza Stark Gene: rad51d has been classified as Green List (High Evidence).
Incidentalome v0.47 RAD51D Elena Savva gene: RAD51D was added
gene: RAD51D was added to Incidentalome. Sources: Literature
Mode of inheritance for gene: RAD51D was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RAD51D were set to PMID: 28646019; 31937788; 26057125
Phenotypes for gene: RAD51D were set to {Breast-ovarian cancer, familial, susceptibility to, 4} 614291
Review for gene: RAD51D was set to GREEN
Added comment: Pure cancer susceptibility gene, no relationship found with germline mutations and other mendelian disease.
Sources: Literature
Differences of Sex Development v0.175 GATA4 Michelle Torres reviewed gene: GATA4: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 21220346, 30455927, 29735817, 27899157, 26490186, 29670578, 32992319; Phenotypes: ?Testicular anomalies with or without congenital heart disease 615542 AD, Atrial septal defect 2 607941 AD, Atrioventricular septal defect 4 614430 AD, Tetralogy of Fallot 187500 AD, Ventricular septal defect 1 614429 AD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Syndromic Retinopathy v0.151 LRRC32 Zornitza Stark Marked gene: LRRC32 as ready
Syndromic Retinopathy v0.151 LRRC32 Zornitza Stark Gene: lrrc32 has been classified as Amber List (Moderate Evidence).
Syndromic Retinopathy v0.151 LRRC32 Zornitza Stark Classified gene: LRRC32 as Amber List (moderate evidence)
Syndromic Retinopathy v0.151 LRRC32 Zornitza Stark Gene: lrrc32 has been classified as Amber List (Moderate Evidence).
Syndromic Retinopathy v0.150 LRRC32 Zornitza Stark gene: LRRC32 was added
gene: LRRC32 was added to Syndromic Retinopathy. Sources: Literature
Mode of inheritance for gene: LRRC32 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRRC32 were set to 30976112
Phenotypes for gene: LRRC32 were set to Cleft palate, proliferative retinopathy, and developmental delay (CPPRDD) syndrome, MIM# 619074
Review for gene: LRRC32 was set to AMBER
Added comment: Three individuals from two consanguineous families segregated the same homozygous bi-allelic variant, c.1630C>T; p.(Arg544Ter), shared haplotype indicative of founder effect. Mouse model has cleft palate and neonatal death.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3125 LRRC32 Zornitza Stark Phenotypes for gene: LRRC32 were changed from Intellectual disability; cleft palate; proliferative retinopathy to Cleft palate, proliferative retinopathy, and developmental delay (CPPRDD) syndrome, MIM# 619074
Intellectual disability syndromic and non-syndromic v0.3124 LRRC32 Zornitza Stark edited their review of gene: LRRC32: Changed phenotypes: Cleft palate, proliferative retinopathy, and developmental delay (CPPRDD) syndrome, MIM# 619074
Mendeliome v0.5192 LRRC32 Zornitza Stark Phenotypes for gene: LRRC32 were changed from Intellectual disability; cleft palate; proliferative retinopathy to Cleft palate, proliferative retinopathy, and developmental delay (CPPRDD) syndrome, MIM# 619074
Mendeliome v0.5191 LRRC32 Zornitza Stark edited their review of gene: LRRC32: Changed phenotypes: Cleft palate, proliferative retinopathy, and developmental delay (CPPRDD) syndrome, MIM# 619074
Syndromic Retinopathy v0.149 ALPK1 Zornitza Stark Marked gene: ALPK1 as ready
Syndromic Retinopathy v0.149 ALPK1 Zornitza Stark Gene: alpk1 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.149 ALPK1 Zornitza Stark Phenotypes for gene: ALPK1 were changed from ROSAH syndrome; retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache to Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache (ROSAH) syndrome, MIM#614979
Syndromic Retinopathy v0.148 ALPK1 Zornitza Stark edited their review of gene: ALPK1: Changed phenotypes: Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache (ROSAH) syndrome, MIM#614979
Mendeliome v0.5191 ALPK1 Zornitza Stark edited their review of gene: ALPK1: Changed phenotypes: Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome, Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache (ROSAH) syndrome, MIM#614979
Mendeliome v0.5191 ALPK1 Zornitza Stark Publications for gene: ALPK1 were set to 31053777
Mendeliome v0.5190 ALPK1 Zornitza Stark Phenotypes for gene: ALPK1 were changed from Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome; Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome ROSAH syndrome, MIM#614979 to Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome; Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache (ROSAH) syndrome, MIM#614979
Mendeliome v0.5189 ALPK1 Zornitza Stark Phenotypes for gene: ALPK1 were changed from Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome; ROSAH syndrome; retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache to Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome; Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome ROSAH syndrome, MIM#614979
Mendeliome v0.5188 ALPK1 Zornitza Stark edited their review of gene: ALPK1: Changed phenotypes: Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome, Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndromeROSAH syndrome, MIM#614979
Genetic Epilepsy v0.895 NUS1 Zornitza Stark Phenotypes for gene: NUS1 were changed from Epilepsy; intellectual disability to Mental retardation, autosomal dominant 55, with seizures, MIM# 617831
Genetic Epilepsy v0.894 NUS1 Zornitza Stark edited their review of gene: NUS1: Changed phenotypes: Mental retardation, autosomal dominant 55, with seizures, MIM# 617831
Intellectual disability syndromic and non-syndromic v0.3124 NUS1 Zornitza Stark Phenotypes for gene: NUS1 were changed from Epilepsy; intellectual disability to Mental retardation, autosomal dominant 55, with seizures, MIM# 617831
Intellectual disability syndromic and non-syndromic v0.3123 NUS1 Zornitza Stark edited their review of gene: NUS1: Changed phenotypes: Mental retardation, autosomal dominant 55, with seizures, MIM# 617831
Mendeliome v0.5188 NUS1 Zornitza Stark Phenotypes for gene: NUS1 were changed from Epilepsy; intellectual disability to Congenital disorder of glycosylation, type 1aa 617082; Mental retardation, autosomal dominant 55, with seizures 617831
Mendeliome v0.5187 NUS1 Zornitza Stark Publications for gene: NUS1 were set to 31656175; 29100083
Mendeliome v0.5186 NUS1 Zornitza Stark Mode of inheritance for gene: NUS1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3123 COG8 Zornitza Stark Marked gene: COG8 as ready
Intellectual disability syndromic and non-syndromic v0.3123 COG8 Zornitza Stark Gene: cog8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3123 COG8 Zornitza Stark Phenotypes for gene: COG8 were changed from to Congenital disorder of glycosylation, type IIh, MIM# 611182
Intellectual disability syndromic and non-syndromic v0.3122 COG8 Zornitza Stark Publications for gene: COG8 were set to
Intellectual disability syndromic and non-syndromic v0.3121 COG8 Zornitza Stark Mode of inheritance for gene: COG8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3120 COG8 Zornitza Stark changed review comment from: Four unrelated families reported with bi-allelic LOF variants and a broad range of predominantly neurological features (ID, seizures, arthrogryposis, brain malformations).

ID present in 3/4, presentation in the 4th family was antenatal but with severe neurological phenotype that would have been expected to result in ID.; to: Four unrelated families reported with bi-allelic LOF variants and a broad range of predominantly neurological features (ID, seizures, arthrogryposis, brain malformations).

ID reported in 3/4, presentation in the 4th family was antenatal but with severe neurological phenotype that would have been expected to result in ID.
Intellectual disability syndromic and non-syndromic v0.3120 COG8 Zornitza Stark reviewed gene: COG8: Rating: GREEN; Mode of pathogenicity: None; Publications: 17220172, 28619360, 30690882, 17331980; Phenotypes: Congenital disorder of glycosylation, type IIh, MIM# 611182; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.180 COG8 Zornitza Stark Marked gene: COG8 as ready
Congenital Disorders of Glycosylation v0.180 COG8 Zornitza Stark Gene: cog8 has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v0.180 COG8 Zornitza Stark Phenotypes for gene: COG8 were changed from to Congenital disorder of glycosylation, type IIh, MIM# 611182
Congenital Disorders of Glycosylation v0.179 COG8 Zornitza Stark Publications for gene: COG8 were set to
Congenital Disorders of Glycosylation v0.178 COG8 Zornitza Stark Mode of inheritance for gene: COG8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.177 COG8 Zornitza Stark reviewed gene: COG8: Rating: GREEN; Mode of pathogenicity: None; Publications: 17220172, 28619360, 30690882, 17331980; Phenotypes: Congenital disorder of glycosylation, type IIh, MIM# 611182; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5185 COG8 Zornitza Stark Marked gene: COG8 as ready
Mendeliome v0.5185 COG8 Zornitza Stark Gene: cog8 has been classified as Green List (High Evidence).
Mendeliome v0.5185 COG8 Zornitza Stark Phenotypes for gene: COG8 were changed from to Congenital disorder of glycosylation, type IIh, MIM# 611182
Mendeliome v0.5184 COG8 Zornitza Stark Publications for gene: COG8 were set to
Mendeliome v0.5183 COG8 Zornitza Stark reviewed gene: COG8: Rating: GREEN; Mode of pathogenicity: None; Publications: 17220172, 28619360; Phenotypes: Congenital disorder of glycosylation, type IIh, MIM# 611182; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5183 COG8 Zornitza Stark Mode of inheritance for gene: COG8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5182 HBB Zornitza Stark Marked gene: HBB as ready
Mendeliome v0.5182 HBB Zornitza Stark Gene: hbb has been classified as Green List (High Evidence).
Mendeliome v0.5182 HBB Zornitza Stark Phenotypes for gene: HBB were changed from to Delta-beta thalassemia 141749; Erythrocytosis 6 617980; Heinz body anemia 140700; Hereditary persistence of fetal hemoglobin 141749; Methemoglobinemia, beta type 617971; Sickle cell anemia 603903; Thalassemia-beta, dominant inclusion-body 603902; Thalassemia, beta 613985
Mendeliome v0.5181 HBB Zornitza Stark Publications for gene: HBB were set to
Mendeliome v0.5180 SCN8A Elena Savva reviewed gene: SCN8A: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID 30615093, 31904124; Phenotypes: ?Myoclonus, familial, 2 618364, Cognitive impairment with or without cerebellar ataxia 614306, Epileptic encephalopathy, early infantile, 13 614558, Seizures, benign familial infantile, 5 617080; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.5180 HBB Zornitza Stark Mode of inheritance for gene: HBB was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.76 ISPD Zornitza Stark Tag SV/CNV tag was added to gene: ISPD.
Muscular dystrophy and myopathy_Paediatric v0.76 ISPD Zornitza Stark edited their review of gene: ISPD: Added comment: - No distinct genotype-phenotype correlation. - Congenital MD is more commonly reported and has been reported in patients with hom PTCs, missense and chet (missense/PTCs) (OMIM). - Limb girdle MD has also been reported for chet patients (PMID: 28688748; PMID: 30060766). Patient fibroblasts showed impaired O-mannosylation, and transfection with wildtype protein have restored function (rescue) (PMID: 22522420). Intragenic CNVs are commonly reported for this gene (OMIM).; Changed publications: 22522421, 23217329, 23390185, 30060766, 28688748, 26404900, 30060766
Mendeliome v0.5179 ISPD Zornitza Stark Tag SV/CNV tag was added to gene: ISPD.
Mendeliome v0.5179 ISPD Zornitza Stark Publications for gene: ISPD were set to 22522421; 23217329; 23390185; 30060766; 28688748; 26404900
Mendeliome v0.5178 RAD51D Zornitza Stark Marked gene: RAD51D as ready
Mendeliome v0.5178 RAD51D Zornitza Stark Gene: rad51d has been classified as Red List (Low Evidence).
Mendeliome v0.5178 RAD51D Zornitza Stark Phenotypes for gene: RAD51D were changed from to {Breast-ovarian cancer, familial, susceptibility to, 4} 614291
Mendeliome v0.5177 RAD51D Zornitza Stark Publications for gene: RAD51D were set to
Mendeliome v0.5176 RAD51D Zornitza Stark Mode of inheritance for gene: RAD51D was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5175 RAD51D Zornitza Stark Classified gene: RAD51D as Red List (low evidence)
Mendeliome v0.5175 RAD51D Zornitza Stark Gene: rad51d has been classified as Red List (Low Evidence).
Mendeliome v0.5174 NUS1 Elena Savva reviewed gene: NUS1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 25066056, 29100083, 31656175, 32485575; Phenotypes: ?Congenital disorder of glycosylation, type 1aa 617082, Mental retardation, autosomal dominant 55, with seizures 617831; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.5174 COG8 Elena Savva reviewed gene: COG8: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30690882, 17331980; Phenotypes: Congenital disorder of glycosylation, type IIh 611182; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5174 HBB Elena Savva reviewed gene: HBB: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31788855, 20301599, 29700171; Phenotypes: {Malaria, resistance to} 611162, Delta-beta thalassemia 141749, Erythrocytosis 6 617980, Heinz body anemia 140700, Hereditary persistence of fetal hemoglobin 141749, Methemoglobinemia, beta type 617971, Sickle cell anemia 603903, Thalassemia-beta, dominant inclusion-body 603902, Thalassemia, beta 613985; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.5174 ISPD Elena Savva reviewed gene: ISPD: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28688748, 30060766, 22522420; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7 614643, Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 7 616052; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5174 TPO Zornitza Stark Marked gene: TPO as ready
Mendeliome v0.5174 TPO Zornitza Stark Gene: tpo has been classified as Green List (High Evidence).
Mendeliome v0.5174 TPO Zornitza Stark Phenotypes for gene: TPO were changed from to Thyroid dyshormonogenesis 2A, MIM# 274500
Mendeliome v0.5173 TPO Zornitza Stark Publications for gene: TPO were set to
Mendeliome v0.5172 TPO Zornitza Stark Mode of inheritance for gene: TPO was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5171 TPO Zornitza Stark reviewed gene: TPO: Rating: GREEN; Mode of pathogenicity: None; Publications: 8027236, 10084596; Phenotypes: Thyroid dyshormonogenesis 2A, MIM# 274500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5171 RAD51D Elena Savva reviewed gene: RAD51D: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 28646019, 31937788, 26057125; Phenotypes: {Breast-ovarian cancer, familial, susceptibility to, 4} 614291; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Congenital Disorders of Glycosylation v0.177 SLC37A4 Zornitza Stark Marked gene: SLC37A4 as ready
Congenital Disorders of Glycosylation v0.177 SLC37A4 Zornitza Stark Gene: slc37a4 has been classified as Red List (Low Evidence).
Congenital Disorders of Glycosylation v0.177 SLC37A4 Zornitza Stark gene: SLC37A4 was added
gene: SLC37A4 was added to Congenital Disorders of Glycosylation. Sources: Literature
Mode of inheritance for gene: SLC37A4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC37A4 were set to 32884905
Phenotypes for gene: SLC37A4 were set to Congenital disorder of glycosylation
Review for gene: SLC37A4 was set to RED
Added comment: Bi-allelic LOF variants in this gene cause glycogen storage disorder.

Single individual reported with heterozygous de novo variant in this gene. Clinical features included dysmorphic features (low set ears, a broad nose, mandibular micrognathia and facial asymmetry) and hepatopathy. The variant abolishes the ER retention signal of the transporter and generates a weak Golgi retention signal. Intracellular mislocalization of the transporter is postulated to lead to a congenital disorder of glycosylation instead of glycogen storage disease.
Sources: Literature
Mendeliome v0.5171 SLC35A3 Zornitza Stark Phenotypes for gene: SLC35A3 were changed from Arthrogryposis, mental retardation, and seizures; OMIM #615553 to Arthrogryposis, mental retardation, and seizures OMIM #615553; Skeletal dysplasia; Congenital disorder of glycosylation
Mendeliome v0.5170 SLC35A3 Zornitza Stark Publications for gene: SLC35A3 were set to 28328131; 24031089
Mendeliome v0.5169 SLC35A3 Zornitza Stark Classified gene: SLC35A3 as Green List (high evidence)
Mendeliome v0.5169 SLC35A3 Zornitza Stark Gene: slc35a3 has been classified as Green List (High Evidence).
Mendeliome v0.5168 SLC35A3 Zornitza Stark edited their review of gene: SLC35A3: Added comment: Third unrelated family reported in PMID 28777481 with prenatally diagnosed anomalous vertebrae, including butterfly, and hemivertebrae throughout the spine, as well as cleft palate, micrognathia, patent foramen ovale, patent ductus arteriosus, posterior embryotoxon, short limbs, camptodactyly, talipes valgus, rocker bottom feet, and facial dysmorphism including proptosis, nevus flammeus, and a cupped left ear. Unclear if this is a distinct phenotype (note Holstein cows with variants in this gene have a skeletal phenotype) or part of a spectrum for a CDG. However, abnormal protein glycosylation, consistent with a defective Golgi UDP-GlcNAc transporter demonstrated, so overall, promoted to Green for CDG.; Changed rating: GREEN; Changed publications: 28777481, 28328131, 24031089; Changed phenotypes: Arthrogryposis, mental retardation, and seizures OMIM #615553, Skeletal dysplasia, Congenital disorder of glycosylation; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.176 SLC35A3 Zornitza Stark Publications for gene: SLC35A3 were set to 28328131; 24031089; 28777481
Congenital Disorders of Glycosylation v0.175 SLC35A3 Zornitza Stark Phenotypes for gene: SLC35A3 were changed from Arthrogryposis, mental retardation, and seizures; OMIM #615553 to Arthrogryposis, mental retardation, and seizures OMIM #615553; Skeletal dysplasia; Congenital disorder of glycosylation
Congenital Disorders of Glycosylation v0.175 SLC35A3 Zornitza Stark Publications for gene: SLC35A3 were set to 28328131; 24031089
Congenital Disorders of Glycosylation v0.174 SLC35A3 Zornitza Stark Classified gene: SLC35A3 as Green List (high evidence)
Congenital Disorders of Glycosylation v0.174 SLC35A3 Zornitza Stark Gene: slc35a3 has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v0.173 SLC35A3 Zornitza Stark edited their review of gene: SLC35A3: Added comment: Third unrelated family reported in PMID 28777481 with prenatally diagnosed anomalous vertebrae, including butterfly, and hemivertebrae throughout the spine, as well as cleft palate, micrognathia, patent foramen ovale, patent ductus arteriosus, posterior embryotoxon, short limbs, camptodactyly, talipes valgus, rocker bottom feet, and facial dysmorphism including proptosis, nevus flammeus, and a cupped left ear. Unclear if this is a distinct phenotype (note Holstein cows with variants in this gene have a skeletal phenotype) or part of a spectrum for a CDG. However, abnormal protein glycosylation, consistent with a defective Golgi UDP-GlcNAc transporter demonstrated, so overall, promoted to Green for CDG.; Changed rating: GREEN; Changed publications: 28777481, 28328131, 24031089; Changed phenotypes: Arthrogryposis, mental retardation, and seizures OMIM #615553, Skeletal dysplasia, Congenital disorder of glycosylation; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3120 SLC35A3 Zornitza Stark Phenotypes for gene: SLC35A3 were changed from ?Arthrogryposis, mental retardation, and seizures; OMIM #615553 to Arthrogryposis, mental retardation, and seizures OMIM #615553; Skeletal dysplasia
Intellectual disability syndromic and non-syndromic v0.3119 SLC35A3 Zornitza Stark Publications for gene: SLC35A3 were set to PMID: 28328131; 24031089
Intellectual disability syndromic and non-syndromic v0.3118 SLC35A3 Zornitza Stark reviewed gene: SLC35A3: Rating: AMBER; Mode of pathogenicity: None; Publications: 28777481; Phenotypes: Skeletal dysplasia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mackenzie's Mission_Reproductive Carrier Screening v0.44 EMG1 Sarah Righetti reviewed gene: EMG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19463982; Phenotypes: Bowen-Conradi syndrome MIM #2111180; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mackenzie's Mission_Reproductive Carrier Screening v0.44 SLC35A3 Sarah Righetti reviewed gene: SLC35A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 24031089, 28777481, 28328131; Phenotypes: Arthrogryposis, mental retardation, and seizures; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Regression v0.202 VAC14 Zornitza Stark Marked gene: VAC14 as ready
Regression v0.202 VAC14 Zornitza Stark Gene: vac14 has been classified as Green List (High Evidence).
Regression v0.202 VAC14 Zornitza Stark Phenotypes for gene: VAC14 were changed from to Striatonigral degeneration, childhood-onset, MIM#617054
Regression v0.201 VAC14 Zornitza Stark Publications for gene: VAC14 were set to
Regression v0.200 VAC14 Zornitza Stark Mode of inheritance for gene: VAC14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5168 VAC14 Zornitza Stark Marked gene: VAC14 as ready
Mendeliome v0.5168 VAC14 Zornitza Stark Gene: vac14 has been classified as Green List (High Evidence).
Regression v0.199 VAC14 Zornitza Stark reviewed gene: VAC14: Rating: GREEN; Mode of pathogenicity: None; Publications: 27292112, 31392254, 31591492, 31387860, 31876398; Phenotypes: Striatonigral degeneration, childhood-onset, MIM#617054; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5168 VAC14 Zornitza Stark Phenotypes for gene: VAC14 were changed from to Striatonigral degeneration, childhood-onset, MIM#617054
Mendeliome v0.5167 VAC14 Zornitza Stark Publications for gene: VAC14 were set to
Mendeliome v0.5166 VAC14 Zornitza Stark Mode of inheritance for gene: VAC14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5165 VAC14 Zornitza Stark reviewed gene: VAC14: Rating: GREEN; Mode of pathogenicity: None; Publications: 27292112, 31392254, 31591492, 31387860, 31876398; Phenotypes: Striatonigral degeneration, childhood-onset, MIM#617054; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mackenzie's Mission_Reproductive Carrier Screening v0.44 ERBB3 Sarah Righetti changed review comment from: PMID 17701904: Lod score >9 in large Israeli family, also a second unrelated isolated case. Both families: hom 8bp insertion. Phenotype similar to that of null mice.

PMID 31752936: Compound het variants identified in 24mo Chinese female patient with a novel multisystem syndrome disorder without congenital contracture

PMID 28454995: Hom missense in Saudi Arabian individual with lethal congenital contractural syndrome, additional features: dysmorphic features, knee dislocation, bilaterial hip dislocation; to: PMID 17701904: Lod score >9 in large Israeli family, also a second unrelated isolated case. Both families: hom splice variant in intron 10 (IVS10-8A→G) causing fs & premature protein truncation. Fnal studies confirm aberrant splicing. Phenotype similar to that of null mice.

PMID 31752936: Compound het variants identified in 24mo Chinese female patient with a novel multisystem syndrome disorder without congenital contracture

PMID 28454995: Hom missense in Saudi Arabian individual with lethal congenital contractural syndrome, additional features: dysmorphic features, knee dislocation, bilaterial hip dislocation
Mackenzie's Mission_Reproductive Carrier Screening v0.44 IL10RB Seb Lunke Marked gene: IL10RB as ready
Mackenzie's Mission_Reproductive Carrier Screening v0.44 IL10RB Seb Lunke Gene: il10rb has been classified as Green List (High Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.44 IL10RB Seb Lunke Classified gene: IL10RB as Green List (high evidence)
Mackenzie's Mission_Reproductive Carrier Screening v0.44 IL10RB Seb Lunke Gene: il10rb has been classified as Green List (High Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.43 PRKRA Seb Lunke Marked gene: PRKRA as ready
Mackenzie's Mission_Reproductive Carrier Screening v0.43 PRKRA Seb Lunke Gene: prkra has been classified as Green List (High Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.43 PRKRA Seb Lunke Classified gene: PRKRA as Green List (high evidence)
Mackenzie's Mission_Reproductive Carrier Screening v0.43 PRKRA Seb Lunke Gene: prkra has been classified as Green List (High Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.42 MSTO1 Seb Lunke Marked gene: MSTO1 as ready
Mackenzie's Mission_Reproductive Carrier Screening v0.42 MSTO1 Seb Lunke Gene: msto1 has been classified as Green List (High Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.42 MSTO1 Seb Lunke Classified gene: MSTO1 as Green List (high evidence)
Mackenzie's Mission_Reproductive Carrier Screening v0.42 MSTO1 Seb Lunke Gene: msto1 has been classified as Green List (High Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.41 XPNPEP3 Seb Lunke Marked gene: XPNPEP3 as ready
Mackenzie's Mission_Reproductive Carrier Screening v0.41 XPNPEP3 Seb Lunke Gene: xpnpep3 has been classified as Amber List (Moderate Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.41 XPNPEP3 Seb Lunke Classified gene: XPNPEP3 as Amber List (moderate evidence)
Mackenzie's Mission_Reproductive Carrier Screening v0.41 XPNPEP3 Seb Lunke Gene: xpnpep3 has been classified as Amber List (Moderate Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.40 UQCRC2 Seb Lunke Marked gene: UQCRC2 as ready
Mackenzie's Mission_Reproductive Carrier Screening v0.40 UQCRC2 Seb Lunke Gene: uqcrc2 has been classified as Red List (Low Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.40 UQCRC2 Seb Lunke Classified gene: UQCRC2 as Red List (low evidence)
Mackenzie's Mission_Reproductive Carrier Screening v0.40 UQCRC2 Seb Lunke Added comment: Comment on list classification: Single variant only, borderline amber for dx, red for screening.
Mackenzie's Mission_Reproductive Carrier Screening v0.40 UQCRC2 Seb Lunke Gene: uqcrc2 has been classified as Red List (Low Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.39 PPIB Seb Lunke Marked gene: PPIB as ready
Mackenzie's Mission_Reproductive Carrier Screening v0.39 PPIB Seb Lunke Gene: ppib has been classified as Green List (High Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.39 PPIB Seb Lunke Classified gene: PPIB as Green List (high evidence)
Mackenzie's Mission_Reproductive Carrier Screening v0.39 PPIB Seb Lunke Gene: ppib has been classified as Green List (High Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.38 GALT Seb Lunke Classified gene: GALT as Green List (high evidence)
Mackenzie's Mission_Reproductive Carrier Screening v0.38 GALT Seb Lunke Gene: galt has been classified as Green List (High Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.37 TUBA8 Seb Lunke Marked gene: TUBA8 as ready
Mackenzie's Mission_Reproductive Carrier Screening v0.37 TUBA8 Seb Lunke Gene: tuba8 has been classified as Red List (Low Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.37 TUBA8 Seb Lunke Classified gene: TUBA8 as Red List (low evidence)
Mackenzie's Mission_Reproductive Carrier Screening v0.37 TUBA8 Seb Lunke Gene: tuba8 has been classified as Red List (Low Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.36 SPEG Seb Lunke Classified gene: SPEG as Green List (high evidence)
Mackenzie's Mission_Reproductive Carrier Screening v0.36 SPEG Seb Lunke Added comment: Comment on list classification: Agreed green gene, update gene selection committee at next meeting.
Mackenzie's Mission_Reproductive Carrier Screening v0.36 SPEG Seb Lunke Gene: speg has been classified as Green List (High Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.35 TSPYL1 Seb Lunke Marked gene: TSPYL1 as ready
Mackenzie's Mission_Reproductive Carrier Screening v0.35 TSPYL1 Seb Lunke Gene: tspyl1 has been classified as Red List (Low Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.35 TSPYL1 Seb Lunke Classified gene: TSPYL1 as Red List (low evidence)
Mackenzie's Mission_Reproductive Carrier Screening v0.35 TSPYL1 Seb Lunke Added comment: Comment on list classification: Agreed amber in diagnostic, but for screening test would need a fair bit of extra evidence.
Mackenzie's Mission_Reproductive Carrier Screening v0.35 TSPYL1 Seb Lunke Gene: tspyl1 has been classified as Red List (Low Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.34 PIP5K1C Seb Lunke Marked gene: PIP5K1C as ready
Mackenzie's Mission_Reproductive Carrier Screening v0.34 PIP5K1C Seb Lunke Gene: pip5k1c has been classified as Red List (Low Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.34 PIP5K1C Seb Lunke Classified gene: PIP5K1C as Red List (low evidence)
Mackenzie's Mission_Reproductive Carrier Screening v0.34 PIP5K1C Seb Lunke Added comment: Comment on list classification: Agreed amber in diagnostic, but for screening test would need a fair bit of extra evidence.
Mackenzie's Mission_Reproductive Carrier Screening v0.34 PIP5K1C Seb Lunke Gene: pip5k1c has been classified as Red List (Low Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.33 VAC14 Sarah Righetti gene: VAC14 was added
gene: VAC14 was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Expert Review
Mode of inheritance for gene: VAC14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VAC14 were set to 27292112; 31392254; 31591492; 31387860; 31876398
Phenotypes for gene: VAC14 were set to Striatonigral degeneration, childhood-onset, MIM#617054
Review for gene: VAC14 was set to GREEN
Added comment: Multiple reports in unrelated patients
Sources: Expert Review
Mackenzie's Mission_Reproductive Carrier Screening v0.33 AFF2 Seb Lunke Marked gene: AFF2 as ready
Mackenzie's Mission_Reproductive Carrier Screening v0.33 AFF2 Seb Lunke Gene: aff2 has been classified as Red List (Low Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.33 AFF2 Seb Lunke Classified gene: AFF2 as Red List (low evidence)
Mackenzie's Mission_Reproductive Carrier Screening v0.33 AFF2 Seb Lunke Gene: aff2 has been classified as Red List (Low Evidence).
Myopathy Superpanel v1.3 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Mackenzie's Mission_Reproductive Carrier Screening v0.32 PRKRA Sarah Righetti gene: PRKRA was added
gene: PRKRA was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Expert Review
Mode of inheritance for gene: PRKRA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRKRA were set to 29279192; 25142429
Phenotypes for gene: PRKRA were set to Dystonia 16, MIM#612067
Review for gene: PRKRA was set to GREEN
Added comment: Sufficient reports - most common variant is c.665C>T p.Pro222Leu, rs121434410

PMID 29279192 (2017)- 7 patients in Brazilian cohort - most homozygous for P222L
PMID 2514249: (2014) - 2 Polish sibs - hom for P222L
Sources: Expert Review
Mackenzie's Mission_Reproductive Carrier Screening v0.32 MSTO1 Sarah Righetti gene: MSTO1 was added
gene: MSTO1 was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Expert Review
Mode of inheritance for gene: MSTO1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MSTO1 were set to 31463572; 30684668
Phenotypes for gene: MSTO1 were set to Myopathy, mitochondrial, and ataxia, MIM#617675
Review for gene: MSTO1 was set to GREEN
Added comment: PMID 31463572: 12 patients
PMID 30684668: 2 sibs - compound het fs and missense.
Sources: Expert Review
Mackenzie's Mission_Reproductive Carrier Screening v0.32 IL10RB Sarah Righetti changed review comment from: Sufficient patients reported (note protein encoded by IL10RB is IL10R2)

19890111: 2 affected sibs with hom stop-gain.
22549091: 8 patients - although a couple where the pathogenicity is in doubt, sufficient overall evidence. Note patient 1 and patient 2 (siblings sharing the same homozygous mutation) had different disease severity) - likely to be other factors which contribute to phenotype.

Severe phenotype.; to: Sufficient patients reported (note protein encoded by IL10RB is IL10R2)

19890111: 2 affected sibs with hom stop-gain.
22549091: 8 patients - although a couple where the pathogenicity is in doubt, sufficient overall evidence. Note patient 1 and patient 2 (siblings sharing the same homozygous mutation) had different disease severity - likely to be other factors which contribute to phenotype.

Severe phenotype.
Mackenzie's Mission_Reproductive Carrier Screening v0.32 IL10RB Sarah Righetti Deleted their comment
Mackenzie's Mission_Reproductive Carrier Screening v0.32 IL10RB Sarah Righetti commented on gene: IL10RB: Sufficient patients reported (note protein encoded by IL10RB is IL10R2)

19890111: 2 affected sibs with hom stop-gain.
22549091: 8 patients - although a couple where the pathogenicity is in doubt, sufficient overall evidence. Note patient 1 and patient 2 (siblings sharing the same homozygous mutation) had different disease severity) - likely to be other factors which contribute to phenotype.

Severe phenotype.
Mackenzie's Mission_Reproductive Carrier Screening v0.32 IL10RB Sarah Righetti reviewed gene: IL10RB: Rating: GREEN; Mode of pathogenicity: None; Publications: 19890111, 22549091; Phenotypes: Inflammatory bowel disease 25, early onset, autosomal recessive, MIM#612567; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mackenzie's Mission_Reproductive Carrier Screening v0.32 IL10RB Sarah Righetti Deleted their review
Mackenzie's Mission_Reproductive Carrier Screening v0.32 IL10RB Sarah Righetti gene: IL10RB was added
gene: IL10RB was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Expert Review
Mode of inheritance for gene: IL10RB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IL10RB were set to 22549091
Phenotypes for gene: IL10RB were set to Inflammatory bowel disease 25, early onset, #MIM612657
Review for gene: IL10RB was set to GREEN
Added comment: Sources: Expert Review
Mackenzie's Mission_Reproductive Carrier Screening v0.32 XPNPEP3 Sarah Righetti reviewed gene: XPNPEP3: Rating: AMBER; Mode of pathogenicity: None; Publications: 20179356, 32660933; Phenotypes: Nephronophthisis-like nephropathy 1, MIM# 613159; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mackenzie's Mission_Reproductive Carrier Screening v0.32 UQCRC2 Sarah Righetti reviewed gene: UQCRC2: Rating: AMBER; Mode of pathogenicity: None; Publications: 28275242, 23281071; Phenotypes: Mitochondrial complex III deficiency, nuclear type 5, MIM# 615160; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mackenzie's Mission_Reproductive Carrier Screening v0.32 PPIB Sarah Righetti changed review comment from: Sources: Expert Review; to: >10 cases across multiple reports, severe phenotype
Mackenzie's Mission_Reproductive Carrier Screening v0.32 PPIB Sarah Righetti gene: PPIB was added
gene: PPIB was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Expert Review
Mode of inheritance for gene: PPIB was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PPIB were set to Osteogenesis imperfecta, type IX, #259440
Review for gene: PPIB was set to GREEN
Added comment: Sources: Expert Review
Mendeliome v0.5165 PHOX2A Zornitza Stark Publications for gene: PHOX2A were set to 11600883; 18323871
Mendeliome v0.5164 PHOX2A Zornitza Stark reviewed gene: PHOX2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 16815872; Phenotypes: Fibrosis of extraocular muscles, congenital, 2 602078; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5164 PHOX2A Zornitza Stark Classified gene: PHOX2A as Green List (high evidence)
Mendeliome v0.5164 PHOX2A Zornitza Stark Gene: phox2a has been classified as Green List (High Evidence).
Mendeliome v0.5163 COL25A1 Zornitza Stark Marked gene: COL25A1 as ready
Mendeliome v0.5163 COL25A1 Zornitza Stark Gene: col25a1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5163 COL25A1 Zornitza Stark Phenotypes for gene: COL25A1 were changed from to Fibrosis of extraocular muscles, congenital, 5, MIM# 616219
Mendeliome v0.5162 COL25A1 Zornitza Stark Publications for gene: COL25A1 were set to
Mendeliome v0.5161 COL25A1 Zornitza Stark Mode of inheritance for gene: COL25A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5160 COL25A1 Zornitza Stark Classified gene: COL25A1 as Amber List (moderate evidence)
Mendeliome v0.5160 COL25A1 Zornitza Stark Gene: col25a1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5159 COL25A1 Zornitza Stark reviewed gene: COL25A1: Rating: AMBER; Mode of pathogenicity: None; Publications: 25500261, 26486031; Phenotypes: Fibrosis of extraocular muscles, congenital, 5, MIM# 616219; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital ophthalmoplegia v0.8 COL25A1 Zornitza Stark Marked gene: COL25A1 as ready
Congenital ophthalmoplegia v0.8 COL25A1 Zornitza Stark Gene: col25a1 has been classified as Amber List (Moderate Evidence).
Congenital ophthalmoplegia v0.8 COL25A1 Zornitza Stark Phenotypes for gene: COL25A1 were changed from Fibrosis of extraocular muscles, congenital, 5; Fibrosis of extraocular muscles, congenital, 5 616219 to Fibrosis of extraocular muscles, congenital, 5, MIM# 616219
Congenital ophthalmoplegia v0.7 COL25A1 Zornitza Stark Publications for gene: COL25A1 were set to 25500261
Mendeliome v0.5159 KIF21A Zornitza Stark Marked gene: KIF21A as ready
Mendeliome v0.5159 KIF21A Zornitza Stark Gene: kif21a has been classified as Green List (High Evidence).
Mendeliome v0.5159 KIF21A Zornitza Stark Phenotypes for gene: KIF21A were changed from to Fibrosis of extraocular muscles, congenital, 1/3B, MIM# 135700
Mendeliome v0.5158 KIF21A Zornitza Stark Publications for gene: KIF21A were set to
Mendeliome v0.5157 KIF21A Zornitza Stark Mode of inheritance for gene: KIF21A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5156 KIF21A Zornitza Stark reviewed gene: KIF21A: Rating: GREEN; Mode of pathogenicity: None; Publications: 15621876, 15223798, 15621877, 18332320, 28930843, 27513105, 26190014, 24656932; Phenotypes: Fibrosis of extraocular muscles, congenital, 1/3B, MIM# 135700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital ophthalmoplegia v0.6 KIF21A Zornitza Stark Marked gene: KIF21A as ready
Congenital ophthalmoplegia v0.6 KIF21A Zornitza Stark Gene: kif21a has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.6 KIF21A Zornitza Stark Phenotypes for gene: KIF21A were changed from Fibrosis of extraocular muscles, congenital, 1, MIM# 135700 to Fibrosis of extraocular muscles, congenital, 1/3B, MIM# 135700
Congenital ophthalmoplegia v0.5 KIF21A Zornitza Stark Phenotypes for gene: KIF21A were changed from Fibrosis of extraocular muscles, congenital, 1 135700; Congenital fibrosis of the extraocular muscles; Fibrosis of extraocular muscles, congenital, 3B 135700 to Fibrosis of extraocular muscles, congenital, 1, MIM# 135700
Congenital ophthalmoplegia v0.4 KIF21A Zornitza Stark Publications for gene: KIF21A were set to 15621876; 15223798; 15621877; 18332320
Congenital ophthalmoplegia v0.3 PHOX2A Zornitza Stark Marked gene: PHOX2A as ready
Congenital ophthalmoplegia v0.3 PHOX2A Zornitza Stark Gene: phox2a has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.3 PHOX2A Zornitza Stark Phenotypes for gene: PHOX2A were changed from Fibrosis of extraocular muscles, congenital, 2 602078; Fibrosis of extraocular muscles, congenital, 2 to Fibrosis of extraocular muscles, congenital, 2, MIM# 602078
Congenital ophthalmoplegia v0.2 PHOX2A Zornitza Stark Publications for gene: PHOX2A were set to 14597037; 22311481; 11600883
Congenital ophthalmoplegia v0.1 TUBB3 Zornitza Stark Marked gene: TUBB3 as ready
Congenital ophthalmoplegia v0.1 TUBB3 Zornitza Stark Gene: tubb3 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.1 TUBB3 Zornitza Stark Publications for gene: TUBB3 were set to 27428177; 20074521
Congenital ophthalmoplegia v0.0 TUBB3 Zornitza Stark reviewed gene: TUBB3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fibrosis of extraocular muscles, congenital, 3A, MIM# 600638; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital ophthalmoplegia v0.0 COL25A1 Shannon LeBlanc reviewed gene: COL25A1: Rating: AMBER; Mode of pathogenicity: None; Publications: OMID: 25500261, 26486031; Phenotypes: Fibrosis of extraocular muscles, congenital, 5, 610004; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital ophthalmoplegia v0.0 PHOX2A Shannon LeBlanc reviewed gene: PHOX2A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 11600883, 14597037, 16815872; Phenotypes: Fibrosis of extraocular muscles, congenital, 2, 602078; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital ophthalmoplegia v0.0 KIF21A Shannon LeBlanc reviewed gene: KIF21A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 14595441, 28930843, 27513105, 26190014, 24656932; Phenotypes: Fibrosis of extraocular muscles, congenital, 1, 135700, Fibrosis of extraocular muscles, congenital, 3B, 135700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital ophthalmoplegia v0.0 TUBB3 Shannon LeBlanc reviewed gene: TUBB3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:27428177, 20074521, 26639658; Phenotypes: Fibrosis of extraocular muscles, congenital, 3A 600638, Cortical dysplasia, complex, with other brain malformations 1, 602661; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Disorders of immune dysregulation v0.70 GATA3 Zornitza Stark Mode of pathogenicity for gene: GATA3 was changed from None to Other
Disorders of immune dysregulation v0.69 GATA3 Zornitza Stark Marked gene: GATA3 as ready
Disorders of immune dysregulation v0.69 GATA3 Zornitza Stark Added comment: Comment when marking as ready: Dominant negative effect proposed.
Disorders of immune dysregulation v0.69 GATA3 Zornitza Stark Gene: gata3 has been classified as Amber List (Moderate Evidence).
Disorders of immune dysregulation v0.69 GATA3 Zornitza Stark Marked gene: GATA3 as ready
Disorders of immune dysregulation v0.69 GATA3 Zornitza Stark Gene: gata3 has been classified as Amber List (Moderate Evidence).
Disorders of immune dysregulation v0.69 GATA3 Zornitza Stark Phenotypes for gene: GATA3 were changed from Hypoparathyroidism, sensorineural deafness, and renal dysplasia MIM#146255 to Immune dysregulation; Hypoparathyroidism, sensorineural deafness, and renal dysplasia MIM#146255
Disorders of immune dysregulation v0.68 GATA3 Zornitza Stark Classified gene: GATA3 as Amber List (moderate evidence)
Disorders of immune dysregulation v0.68 GATA3 Zornitza Stark Gene: gata3 has been classified as Amber List (Moderate Evidence).
Mitochondrial disease v0.550 NDUFAF6 Zornitza Stark Marked gene: NDUFAF6 as ready
Mitochondrial disease v0.550 NDUFAF6 Zornitza Stark Gene: ndufaf6 has been classified as Green List (High Evidence).
Mitochondrial disease v0.550 NDUFAF6 Zornitza Stark Phenotypes for gene: NDUFAF6 were changed from to Mitochondrial complex I deficiency, nuclear type 17 (MIM#618239)
Mitochondrial disease v0.549 NDUFAF6 Zornitza Stark Publications for gene: NDUFAF6 were set to
Mitochondrial disease v0.548 NDUFAF6 Zornitza Stark Mode of inheritance for gene: NDUFAF6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5156 NDUFAF6 Zornitza Stark Marked gene: NDUFAF6 as ready
Mendeliome v0.5156 NDUFAF6 Zornitza Stark Gene: ndufaf6 has been classified as Green List (High Evidence).
Mendeliome v0.5156 NDUFAF6 Zornitza Stark Phenotypes for gene: NDUFAF6 were changed from to Mitochondrial complex I deficiency, nuclear type 17 (MIM#618239)
Mendeliome v0.5155 NDUFAF6 Zornitza Stark Publications for gene: NDUFAF6 were set to
Mendeliome v0.5154 NDUFAF6 Zornitza Stark Mode of inheritance for gene: NDUFAF6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v1.13 USH1C Zornitza Stark Phenotypes for gene: USH1C were changed from Usher syndrome, type 1C, MIM# 276904; Deafness, autosomal recessive 18A, MIM# 602092 to Usher syndrome, type 1C, MIM# 276904; Deafness, autosomal recessive 18A, MIM# 602092; Deafness, autosomal dominant
Deafness_IsolatedAndComplex v1.12 USH1C Zornitza Stark Publications for gene: USH1C were set to 10973247; 10973248; 11239869; 21203349; 12107438
Deafness_IsolatedAndComplex v1.11 USH1C Zornitza Stark Mode of inheritance for gene: USH1C was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mitochondrial disease v0.547 NDUFAF6 Ain Roesley reviewed gene: NDUFAF6: Rating: GREEN; Mode of pathogenicity: None; Publications: 30642748; Phenotypes: Mitochondrial complex I deficiency, nuclear type 17 (MIM#618239); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5153 NDUFAF6 Ain Roesley reviewed gene: NDUFAF6: Rating: GREEN; Mode of pathogenicity: None; Publications: 30642748; Phenotypes: Mitochondrial complex I deficiency, nuclear type 17 (MIM#618239); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v1.10 USH1C Elena Savva reviewed gene: USH1C: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31858762, 10973247, 10973248, 11239869, 21203349, 12107438; Phenotypes: Usher syndrome, type 1C, MIM# 276904, Deafness, autosomal recessive 18A, MIM# 602092, ?Non-syndromic hearing loss; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5153 WNT5A Zornitza Stark Marked gene: WNT5A as ready
Mendeliome v0.5153 WNT5A Zornitza Stark Gene: wnt5a has been classified as Green List (High Evidence).
Mendeliome v0.5153 WNT5A Zornitza Stark Phenotypes for gene: WNT5A were changed from to Robinow syndrome, autosomal dominant 1, MIM#180700
Mendeliome v0.5152 WNT5A Zornitza Stark Publications for gene: WNT5A were set to
Mendeliome v0.5151 WNT5A Zornitza Stark Mode of inheritance for gene: WNT5A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5150 WNT5A Zornitza Stark reviewed gene: WNT5A: Rating: GREEN; Mode of pathogenicity: None; Publications: 19918918, 24716670, 27092434, 29276006, 31032853, 16602827, 12839624, 10021340; Phenotypes: Robinow syndrome, autosomal dominant 1, MIM#180700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5150 CYP3A4 Zornitza Stark Marked gene: CYP3A4 as ready
Mendeliome v0.5150 CYP3A4 Zornitza Stark Gene: cyp3a4 has been classified as Green List (High Evidence).
Mendeliome v0.5150 CYP3A4 Zornitza Stark Phenotypes for gene: CYP3A4 were changed from to Vitamin D-dependent rickets-3, MIM#619073
Mendeliome v0.5149 CYP3A4 Zornitza Stark Publications for gene: CYP3A4 were set to
Mendeliome v0.5148 CYP3A4 Zornitza Stark Mode of pathogenicity for gene: CYP3A4 was changed from to Other
Mendeliome v0.5147 CYP3A4 Zornitza Stark Mode of inheritance for gene: CYP3A4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5146 CYP3A4 Zornitza Stark reviewed gene: CYP3A4: Rating: GREEN; Mode of pathogenicity: Other; Publications: 29461981; Phenotypes: Vitamin D-dependent rickets-3, MIM#619073; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Disorders of immune dysregulation v0.67 GATA3 Elena Savva gene: GATA3 was added
gene: GATA3 was added to Disorders of immune dysregulation. Sources: Literature
Mode of inheritance for gene: GATA3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: GATA3 were set to PMID: 31238969
Phenotypes for gene: GATA3 were set to Hypoparathyroidism, sensorineural deafness, and renal dysplasia MIM#146255
Review for gene: GATA3 was set to AMBER
gene: GATA3 was marked as current diagnostic
Added comment: PMID: 31238969: patient with protein elongation variant p.(M401Vfs*106) has an additional phenotype of juvenile idiopathic arthritis. Functional studies on the variant support pathogenicity, and analysis of patient cells indicate defective T helper cell differentiation and cytokine production.
Sources: Literature
Mendeliome v0.5146 KCTD17 Zornitza Stark Marked gene: KCTD17 as ready
Mendeliome v0.5146 KCTD17 Zornitza Stark Gene: kctd17 has been classified as Green List (High Evidence).
Mendeliome v0.5146 KCTD17 Zornitza Stark Phenotypes for gene: KCTD17 were changed from to Dystonia 26, myoclonic MIM#616398
Mendeliome v0.5145 KCTD17 Zornitza Stark Publications for gene: KCTD17 were set to
Mendeliome v0.5144 KCTD17 Zornitza Stark Mode of inheritance for gene: KCTD17 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5143 KCTD17 Zornitza Stark reviewed gene: KCTD17: Rating: GREEN; Mode of pathogenicity: None; Publications: 25983243, 30642807, 30579817; Phenotypes: Dystonia 26, myoclonic MIM#616398; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5143 TAF1 Zornitza Stark Tag deep intronic tag was added to gene: TAF1.
Tag founder tag was added to gene: TAF1.
Mendeliome v0.5143 TAF1 Zornitza Stark Marked gene: TAF1 as ready
Mendeliome v0.5143 TAF1 Zornitza Stark Gene: taf1 has been classified as Green List (High Evidence).
Mendeliome v0.5143 TAF1 Zornitza Stark Phenotypes for gene: TAF1 were changed from to Dystonia-Parkinsonism, X-linked, MIM# 314250; Mental retardation, X-linked, syndromic 33, MIM# 300966
Mendeliome v0.5142 TAF1 Zornitza Stark Publications for gene: TAF1 were set to
Mendeliome v0.5141 TAF1 Zornitza Stark Mode of inheritance for gene: TAF1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.5140 TAF1 Zornitza Stark reviewed gene: TAF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 17273961, 31646703; Phenotypes: Dystonia-Parkinsonism, X-linked, MIM# 314250, Mental retardation, X-linked, syndromic 33, MIM# 300966; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.5140 CTNNA3 Bryony Thompson Marked gene: CTNNA3 as ready
Mendeliome v0.5140 CTNNA3 Bryony Thompson Gene: ctnna3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5140 CTNNA3 Bryony Thompson Classified gene: CTNNA3 as Amber List (moderate evidence)
Mendeliome v0.5140 CTNNA3 Bryony Thompson Gene: ctnna3 has been classified as Amber List (Moderate Evidence).
Arrhythmogenic Cardiomyopathy v0.47 CTNNA3 Bryony Thompson changed review comment from: Gene is classified as Limited by the ClinGen ARVC GCEP (Classification - 08/06/2019).
PMID: 23136403 - an assumed de novo missense (V94D) was identified in an Italian proband with arrhythmogenic right ventricular dysplasia. An inframe deletion (Leu765del) was identified in a proband with arrhythmogenic right ventricular dysplasia, and was also present in the proband's asymptomatic father and paternal aunt, who had mild right ventricular dilation on echocardiography and increased trabeculations in the right ventricular apex on MRI, respectively, as well as in the aunt's asymptomatic son. There was supporting in vitro functional assay evidence for both variants. PMID: 21254927 - a missense variant was found in one of 55 Danish ARVD patients, but was found 37 times in 276,338 (1 homozygous) reference alleles in gnomAD making it less likely as a causal variant. PMID: 22421363 - null mice exhibit progressive dilated cardiomyopathy, gap junction remodelling, and increased sensitivity to ventricular arrhythmia following acute ischaemia, but not spontaneous ARVC.
PMID: 30415094 - a VUS identified in a sudden unexpected death case with slight LV hypertrophy. PMID: 31539150 - 2 VUS and a nonsense variant identified in 3 probands with atrial fibrillation, with the nonsense variant segregating in an affected first-degree relative.
Sources: Other; to: Gene is classified as Limited by the ClinGen ARVC GCEP (Classification - 08/06/2019).
PMID: 23136403 - an assumed de novo missense (V94D) was identified in an Italian proband with arrhythmogenic right ventricular dysplasia. An inframe deletion (Leu765del) was identified in a proband with arrhythmogenic right ventricular dysplasia, and was also present in the proband's asymptomatic father and paternal aunt, who had mild right ventricular dilation on echocardiography and increased trabeculations in the right ventricular apex on MRI, respectively, as well as in the aunt's asymptomatic son. There was supporting in vitro functional assay evidence for both variants. PMID: 21254927 - a missense variant was found in one of 55 Danish ARVD patients, but was found 37 times in 276,338 (1 homozygous) reference alleles in gnomAD making it less likely as a causal variant. PMID: 22421363 - null mice exhibit progressive dilated cardiomyopathy, gap junction remodelling, and increased sensitivity to ventricular arrhythmia following acute ischaemia, but not spontaneous ARVC.
Additional publications identified - PMID: 30415094 - a VUS identified in a sudden unexpected death case with slight LV hypertrophy. PMID: 31539150 - 2 VUS and a nonsense variant identified in 3 probands with atrial fibrillation, with the nonsense variant segregating in an affected first-degree relative.
Sources: Other
Mendeliome v0.5139 CTNNA3 Bryony Thompson gene: CTNNA3 was added
gene: CTNNA3 was added to Mendeliome. Sources: ClinGen
Mode of inheritance for gene: CTNNA3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CTNNA3 were set to 23136403; 21254927; 22421363; 30415094; 31539150
Phenotypes for gene: CTNNA3 were set to Arrhythmogenic right ventricular cardiomyopathy; Arrhythmogenic right ventricular dysplasia, familial, 13 MIM#615616
Review for gene: CTNNA3 was set to AMBER
Added comment: Gene is classified as Limited by the ClinGen ARVC GCEP (Classification - 08/06/2019). PMID: 23136403 - an assumed de novo missense (V94D) was identified in an Italian proband with arrhythmogenic right ventricular dysplasia. An inframe deletion (Leu765del) was identified in a proband with arrhythmogenic right ventricular dysplasia, and was also present in the proband's asymptomatic father and paternal aunt, who had mild right ventricular dilation on echocardiography and increased trabeculations in the right ventricular apex on MRI, respectively, as well as in the aunt's asymptomatic son. There was supporting in vitro functional assay evidence for both variants. PMID: 21254927 - a missense variant was found in one of 55 Danish ARVD patients, but was found 37 times in 276,338 (1 homozygous) reference alleles in gnomAD making it less likely as a causal variant. PMID: 22421363 - null mice exhibit progressive dilated cardiomyopathy, gap junction remodelling, and increased sensitivity to ventricular arrhythmia following acute ischaemia, but not spontaneous ARVC. Additional publications identified - PMID: 30415094 - a VUS identified in a sudden unexpected death case with slight LV hypertrophy. PMID: 31539150 - 2 VUS and a nonsense variant identified in 3 probands with atrial fibrillation, with the nonsense variant segregating in an affected first-degree relative.
Sources: ClinGen
Arrhythmogenic Cardiomyopathy v0.47 CTNNA3 Bryony Thompson Classified gene: CTNNA3 as Amber List (moderate evidence)
Arrhythmogenic Cardiomyopathy v0.47 CTNNA3 Bryony Thompson Gene: ctnna3 has been classified as Amber List (Moderate Evidence).
Arrhythmogenic Cardiomyopathy v0.46 CTNNA3 Bryony Thompson gene: CTNNA3 was added
gene: CTNNA3 was added to Arrhythmogenic Cardiomyopathy. Sources: Other
Mode of inheritance for gene: CTNNA3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CTNNA3 were set to 23136403; 21254927; 22421363; 30415094; 31539150
Phenotypes for gene: CTNNA3 were set to Arrhythmogenic right ventricular cardiomyopathy; Arrhythmogenic right ventricular dysplasia, familial, 13 MIM#615616
Review for gene: CTNNA3 was set to AMBER
Added comment: Gene is classified as Limited by the ClinGen ARVC GCEP (Classification - 08/06/2019).
PMID: 23136403 - an assumed de novo missense (V94D) was identified in an Italian proband with arrhythmogenic right ventricular dysplasia. An inframe deletion (Leu765del) was identified in a proband with arrhythmogenic right ventricular dysplasia, and was also present in the proband's asymptomatic father and paternal aunt, who had mild right ventricular dilation on echocardiography and increased trabeculations in the right ventricular apex on MRI, respectively, as well as in the aunt's asymptomatic son. There was supporting in vitro functional assay evidence for both variants. PMID: 21254927 - a missense variant was found in one of 55 Danish ARVD patients, but was found 37 times in 276,338 (1 homozygous) reference alleles in gnomAD making it less likely as a causal variant. PMID: 22421363 - null mice exhibit progressive dilated cardiomyopathy, gap junction remodelling, and increased sensitivity to ventricular arrhythmia following acute ischaemia, but not spontaneous ARVC.
PMID: 30415094 - a VUS identified in a sudden unexpected death case with slight LV hypertrophy. PMID: 31539150 - 2 VUS and a nonsense variant identified in 3 probands with atrial fibrillation, with the nonsense variant segregating in an affected first-degree relative.
Sources: Other
Ataxia v0.265 NUS1 Zornitza Stark Marked gene: NUS1 as ready
Ataxia v0.265 NUS1 Zornitza Stark Gene: nus1 has been classified as Green List (High Evidence).
Ataxia v0.265 NUS1 Zornitza Stark Phenotypes for gene: NUS1 were changed from Epilepsy, myoclonus, ataxia and scoliosis; ?Congenital disorder of glycosylation, type 1aa, 617082; Mental retardation, autosomal dominant 55, with seizures, 617831 to Epilepsy, myoclonus, ataxia and scoliosis; Mental retardation, autosomal dominant 55, with seizures, 617831
Ataxia v0.264 NUS1 Zornitza Stark Classified gene: NUS1 as Green List (high evidence)
Ataxia v0.264 NUS1 Zornitza Stark Gene: nus1 has been classified as Green List (High Evidence).
Ataxia v0.263 NUS1 Elena Savva gene: NUS1 was added
gene: NUS1 was added to Ataxia - paediatric. Sources: Literature
Mode of inheritance for gene: NUS1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NUS1 were set to PMID: 31656175; 29100083
Phenotypes for gene: NUS1 were set to Epilepsy, myoclonus, ataxia and scoliosis; ?Congenital disorder of glycosylation, type 1aa, 617082; Mental retardation, autosomal dominant 55, with seizures, 617831
Review for gene: NUS1 was set to GREEN
Added comment: PMID: 31656175 - 2 unrelated patients with the same de novo splice variant and ataxia. Splice variant undergoes partial NMD.

PMID: 29100083 - 3 unrelated patients w/ 2 PTCs and an inframe exon 2 deletion. Only 1/3 was reported to have ataxia
Sources: Literature
Brain Channelopathies v0.32 ADCY5 Zornitza Stark Marked gene: ADCY5 as ready
Brain Channelopathies v0.32 ADCY5 Zornitza Stark Gene: adcy5 has been classified as Green List (High Evidence).
Brain Channelopathies v0.32 ADCY5 Zornitza Stark Phenotypes for gene: ADCY5 were changed from to Dyskinesia, familial, with facial myokymia, MIM# 606703
Brain Channelopathies v0.31 ADCY5 Zornitza Stark Publications for gene: ADCY5 were set to
Brain Channelopathies v0.30 ADCY5 Zornitza Stark Mode of inheritance for gene: ADCY5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brain Channelopathies v0.29 ADCY5 Zornitza Stark reviewed gene: ADCY5: Rating: GREEN; Mode of pathogenicity: None; Publications: 24700542, 22782511, 16537460; Phenotypes: Dyskinesia, familial, with facial myokymia, MIM# 606703; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Myasthenia v1.0 Zornitza Stark promoted panel to version 1.0
Holoprosencephaly and septo-optic dysplasia v0.48 SHH Zornitza Stark Marked gene: SHH as ready
Holoprosencephaly and septo-optic dysplasia v0.48 SHH Zornitza Stark Gene: shh has been classified as Green List (High Evidence).
Holoprosencephaly and septo-optic dysplasia v0.48 SHH Zornitza Stark Phenotypes for gene: SHH were changed from to Holoprosencephaly 3 (MIM#142945)
Holoprosencephaly and septo-optic dysplasia v0.47 SHH Zornitza Stark Publications for gene: SHH were set to
Holoprosencephaly and septo-optic dysplasia v0.46 SHH Zornitza Stark Mode of inheritance for gene: SHH was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hydrocephalus_Ventriculomegaly v0.70 COG8 Zornitza Stark Marked gene: COG8 as ready
Hydrocephalus_Ventriculomegaly v0.70 COG8 Zornitza Stark Gene: cog8 has been classified as Red List (Low Evidence).
Hydrocephalus_Ventriculomegaly v0.70 COG8 Zornitza Stark Classified gene: COG8 as Red List (low evidence)
Hydrocephalus_Ventriculomegaly v0.70 COG8 Zornitza Stark Gene: cog8 has been classified as Red List (Low Evidence).
Arthrogryposis v0.239 COG8 Zornitza Stark Marked gene: COG8 as ready
Arthrogryposis v0.239 COG8 Zornitza Stark Gene: cog8 has been classified as Red List (Low Evidence).
Arthrogryposis v0.239 COG8 Zornitza Stark Classified gene: COG8 as Red List (low evidence)
Arthrogryposis v0.239 COG8 Zornitza Stark Gene: cog8 has been classified as Red List (Low Evidence).
Holoprosencephaly and septo-optic dysplasia v0.45 SHH Teresa Zhao reviewed gene: SHH: Rating: GREEN; Mode of pathogenicity: None; Publications: 22791840, 19057928; Phenotypes: 1. Holoprosencephaly 3 (MIM#142945), AD, 2. Microphthalmia with coloboma 5 (MIM#611638), AD, 3. Schizencephaly (MIM#269160), 4. Single median maxillary central incisor (MIM#147250) AD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hydrocephalus_Ventriculomegaly v0.69 COG8 Elena Savva gene: COG8 was added
gene: COG8 was added to Hydrocephalus_Ventriculomegaly. Sources: Literature
Mode of inheritance for gene: COG8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COG8 were set to PMID: 30690882
Phenotypes for gene: COG8 were set to Congenital disorder of glycosylation, type IIh 611182
Review for gene: COG8 was set to RED
Added comment: PMID: 30690882: single patient with a homozygous splice COG8 variant, sibling was similarly affected but no DNA available. Patient displayed antenatal phenotype arthrogryposis multiplex congenita, Dandy Walker malformation and ventriculomegaly.
Sources: Literature
Arthrogryposis v0.238 COG8 Elena Savva gene: COG8 was added
gene: COG8 was added to Arthrogryposis. Sources: Literature
Mode of inheritance for gene: COG8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COG8 were set to PMID: 30690882
Phenotypes for gene: COG8 were set to Congenital disorder of glycosylation, type IIh 611182
Review for gene: COG8 was set to RED
Added comment: PMID: 30690882: single patient with a homozygous splice COG8 variant, sibling was similarly affected but no DNA available. Patient displayed antenatal phenotype arthrogryposis multiplex congenita, Dandy Walker malformation and ventriculomegaly.
Sources: Literature
Genetic Epilepsy v0.894 STXBP1 Zornitza Stark Phenotypes for gene: STXBP1 were changed from Epileptic encephalopathy, early infantile, 4, MIM#612164 to Developmental and epileptic encephalopathy 4, MIM# 612164
Genetic Epilepsy v0.893 STXBP1 Zornitza Stark edited their review of gene: STXBP1: Changed phenotypes: Developmental and epileptic encephalopathy 4, MIM# 612164
Mendeliome v0.5138 STXBP1 Zornitza Stark Phenotypes for gene: STXBP1 were changed from Epileptic encephalopathy, early infantile, 4 612164; Rett syndrome; Rett-like phenotypes to Developmental and epileptic encephalopathy 4, MIM# 612164; Rett syndrome; Rett-like phenotypes
Mendeliome v0.5137 STXBP1 Zornitza Stark reviewed gene: STXBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 4, MIM# 612164; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Angelman Rett like syndromes v0.24 STXBP1 Zornitza Stark Marked gene: STXBP1 as ready
Angelman Rett like syndromes v0.24 STXBP1 Zornitza Stark Gene: stxbp1 has been classified as Green List (High Evidence).
Angelman Rett like syndromes v0.24 STXBP1 Zornitza Stark Phenotypes for gene: STXBP1 were changed from to Developmental and epileptic encephalopathy 4, MIM# 612164
Angelman Rett like syndromes v0.23 STXBP1 Zornitza Stark Publications for gene: STXBP1 were set to
Angelman Rett like syndromes v0.22 STXBP1 Zornitza Stark Mode of inheritance for gene: STXBP1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Angelman Rett like syndromes v0.21 STXBP1 Zornitza Stark reviewed gene: STXBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31344879; Phenotypes: Developmental and epileptic encephalopathy 4, MIM# 612164; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5137 UBE3A Zornitza Stark Tag SV/CNV tag was added to gene: UBE3A.
Mendeliome v0.5137 UBE3A Zornitza Stark Phenotypes for gene: UBE3A were changed from to Angelman syndrome, MIM#105830
Mendeliome v0.5136 UBE3A Zornitza Stark Mode of inheritance for gene: UBE3A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Mendeliome v0.5135 UBE3A Zornitza Stark reviewed gene: UBE3A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Angelman syndrome, MIM#105830; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Angelman Rett like syndromes v0.21 UBE3A Zornitza Stark Tag SV/CNV tag was added to gene: UBE3A.
Microcephaly v0.495 UBE3A Zornitza Stark Mode of inheritance for gene: UBE3A was changed from MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed) to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Microcephaly v0.494 UBE3A Zornitza Stark Tag SV/CNV tag was added to gene: UBE3A.
Microcephaly v0.494 UBE3A Zornitza Stark edited their review of gene: UBE3A: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Angelman Rett like syndromes v0.21 UBE3A Zornitza Stark Phenotypes for gene: UBE3A were changed from Angelman syndrome, MIM#105830 to Angelman syndrome, MIM#105830
Angelman Rett like syndromes v0.21 UBE3A Zornitza Stark Phenotypes for gene: UBE3A were changed from to Angelman syndrome, MIM#105830
Angelman Rett like syndromes v0.20 UBE3A Zornitza Stark Mode of inheritance for gene: UBE3A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Angelman Rett like syndromes v0.19 UBE3A Zornitza Stark reviewed gene: UBE3A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Angelman syndrome, MIM#105830; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Mendeliome v0.5135 CHRNE Zornitza Stark Marked gene: CHRNE as ready
Mendeliome v0.5135 CHRNE Zornitza Stark Gene: chrne has been classified as Green List (High Evidence).
Mendeliome v0.5135 CHRNE Zornitza Stark Phenotypes for gene: CHRNE were changed from to Myasthenic syndrome, congenital, 4B, fast-channel, 616324; Myasthenic syndrome, congenital, 4C, associated with acetylcholine receptor deficiency, 608931; Myasthenic syndrome, slow-channel congenital, 601462; Myasthenic syndrome, congenital, 4A, slow-channel, 605809
Mendeliome v0.5134 CHRNE Zornitza Stark Publications for gene: CHRNE were set to
Mendeliome v0.5133 CHRNE Zornitza Stark Mode of inheritance for gene: CHRNE was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5132 CHRNE Zornitza Stark reviewed gene: CHRNE: Rating: GREEN; Mode of pathogenicity: None; Publications: 8755487, 8957026, 11030414, 12417530, 32727330, 32070632, 31773638; Phenotypes: Myasthenic syndrome, congenital, 4B, fast-channel, 616324, Myasthenic syndrome, congenital, 4C, associated with acetylcholine receptor deficiency, 608931, Myasthenic syndrome, slow-channel congenital, 601462, Myasthenic syndrome, congenital, 4A, slow-channel, 605809; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital Myasthenia v0.50 CHRNE Zornitza Stark Marked gene: CHRNE as ready
Congenital Myasthenia v0.50 CHRNE Zornitza Stark Gene: chrne has been classified as Green List (High Evidence).
Congenital Myasthenia v0.50 CHRNE Zornitza Stark Publications for gene: CHRNE were set to
Congenital Myasthenia v0.49 CHRNE Zornitza Stark edited their review of gene: CHRNE: Changed phenotypes: Myasthenic syndrome, congenital, 4B, fast-channel, 616324, Myasthenic syndrome, congenital, 4C, associated with acetylcholine receptor deficiency, 608931, Myasthenic syndrome, slow-channel congenital, 601462, Myasthenic syndrome, congenital, 4A, slow-channel, 605809
Congenital Myasthenia v0.49 CHRNE Zornitza Stark reviewed gene: CHRNE: Rating: GREEN; Mode of pathogenicity: None; Publications: 8755487, 8957026, 11030414, 12417530, 32727330, 32070632, 31773638; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital Myasthenia v0.49 CHRND Zornitza Stark Marked gene: CHRND as ready
Congenital Myasthenia v0.49 CHRND Zornitza Stark Gene: chrnd has been classified as Green List (High Evidence).
Congenital Myasthenia v0.49 CHRND Zornitza Stark Phenotypes for gene: CHRND were changed from Myasthenic syndrome, congenital, 3B, fast-channel, 616322; Myasthenic syndrome, slow-channel congenital, 601462; ?Myasthenic syndrome, congenital, 3A, slow-channel, 616321; ?Myasthenic syndrome, congenital, 3C, associated with acetylcholine receptor deficiency, 616323 to Myasthenic syndrome, congenital, 3B, fast-channel, MIM#616322; Myasthenic syndrome, congenital, 3C, associated with acetylcholine receptor deficiency, MIM#616323; Myasthenic syndrome, congenital, 3A, slow-channel, MIM#616321
Congenital Myasthenia v0.48 CHRND Zornitza Stark Publications for gene: CHRND were set to
Congenital Myasthenia v0.47 CHRND Zornitza Stark edited their review of gene: CHRND: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital Myasthenia v0.47 CHRND Zornitza Stark reviewed gene: CHRND: Rating: GREEN; Mode of pathogenicity: None; Publications: 16916845, 11435464, 12499478, 18398509, 11782989; Phenotypes: Myasthenic syndrome, congenital, 3B, fast-channel, MIM#616322, Myasthenic syndrome, congenital, 3C, associated with acetylcholine receptor deficiency, MIM#616323, Myasthenic syndrome, congenital, 3A, slow-channel, MIM#616321; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5132 COLQ Zornitza Stark Marked gene: COLQ as ready
Mendeliome v0.5132 COLQ Zornitza Stark Gene: colq has been classified as Green List (High Evidence).
Mendeliome v0.5132 COLQ Zornitza Stark Phenotypes for gene: COLQ were changed from to Myasthenic syndrome, congenital, 5, MIM# 603034
Mendeliome v0.5131 COLQ Zornitza Stark Publications for gene: COLQ were set to
Mendeliome v0.5130 COLQ Zornitza Stark Mode of inheritance for gene: COLQ was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5129 COLQ Zornitza Stark reviewed gene: COLQ: Rating: GREEN; Mode of pathogenicity: None; Publications: 9689136, 9758617, 11865139, 32978031, 31831253; Phenotypes: Myasthenic syndrome, congenital, 5, MIM# 603034; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Myasthenia v0.47 COLQ Zornitza Stark Marked gene: COLQ as ready
Congenital Myasthenia v0.47 COLQ Zornitza Stark Gene: colq has been classified as Green List (High Evidence).
Congenital Myasthenia v0.47 COLQ Zornitza Stark Phenotypes for gene: COLQ were changed from Myasthenic syndrome, congenital, 5, 603034; Congenital myasthenic syndrome with endplate acetylcholinesterase deficiency to Myasthenic syndrome, congenital, 5, MIM# 603034; Congenital myasthenic syndrome with endplate acetylcholinesterase deficiency
Congenital Myasthenia v0.46 COLQ Zornitza Stark Publications for gene: COLQ were set to
Congenital Myasthenia v0.45 COLQ Zornitza Stark reviewed gene: COLQ: Rating: GREEN; Mode of pathogenicity: None; Publications: 9689136, 9758617, 11865139, 32978031, 31831253; Phenotypes: Myasthenic syndrome, congenital, 5, MIM# 603034; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Myasthenia v0.45 CHRNG Zornitza Stark Marked gene: CHRNG as ready
Congenital Myasthenia v0.45 CHRNG Zornitza Stark Gene: chrng has been classified as Green List (High Evidence).
Congenital Myasthenia v0.45 CHRNG Zornitza Stark Phenotypes for gene: CHRNG were changed from fetal akinesia deformation sequence syndrome/FADS; multiple pterygium syndrome/MPS; Neonatal congenital myasthenia; escobar syndrome; Myasthenia gravis, neonatal transient to Multiple pterygium syndrome, lethal type, MIM# 253290; fetal akinesia deformation sequence syndrome/FADS; multiple pterygium syndrome/MPS; Neonatal congenital myasthenia; escobar syndrome; Myasthenia gravis, neonatal transient
Congenital Myasthenia v0.44 CHRNG Zornitza Stark Publications for gene: CHRNG were set to
Congenital Myasthenia v0.43 CHRNG Zornitza Stark reviewed gene: CHRNG: Rating: GREEN; Mode of pathogenicity: None; Publications: 22167768; Phenotypes: Multiple pterygium syndrome, lethal type, MIM# 253290; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v0.38 NDUFA4 Zornitza Stark Marked gene: NDUFA4 as ready
Cardiomyopathy_Paediatric v0.38 NDUFA4 Zornitza Stark Gene: ndufa4 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v0.38 NDUFA4 Zornitza Stark Phenotypes for gene: NDUFA4 were changed from No OMIM phenotype to Mitochondrial complex IV deficiency, nuclear type 21, MIM#619065
Cardiomyopathy_Paediatric v0.37 NDUFA4 Zornitza Stark Publications for gene: NDUFA4 were set to 23746447, 29636225
Cardiomyopathy_Paediatric v0.36 NDUFA4 Zornitza Stark Classified gene: NDUFA4 as Red List (low evidence)
Cardiomyopathy_Paediatric v0.36 NDUFA4 Zornitza Stark Gene: ndufa4 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v0.35 NDUFA4 Zornitza Stark reviewed gene: NDUFA4: Rating: RED; Mode of pathogenicity: None; Publications: 30361421, 28988874, 23746447; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 21, MIM#619065; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Regression v0.199 NDUFA4 Zornitza Stark Phenotypes for gene: NDUFA4 were changed from Leigh syndrome; Complex IV deficiency to Mitochondrial complex IV deficiency, nuclear type 21, MIM#619065; Leigh syndrome; Complex IV deficiency
Regression v0.199 NDUFA4 Zornitza Stark Mode of inheritance for gene: NDUFA4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Regression v0.198 NDUFA4 Zornitza Stark edited their review of gene: NDUFA4: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 21, MIM#619065, Leigh syndrome, Complex IV deficiency
Mendeliome v0.5129 NDUFA4 Zornitza Stark Phenotypes for gene: NDUFA4 were changed from Leigh syndrome; Complex IV deficiency to Mitochondrial complex IV deficiency, nuclear type 21, MIM#619065; Leigh syndrome; Complex IV deficiency
Mendeliome v0.5128 NDUFA4 Zornitza Stark edited their review of gene: NDUFA4: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 21, MIM#619065, Leigh syndrome, Complex IV deficiency
Mitochondrial disease v0.547 NDUFA4 Zornitza Stark edited their review of gene: NDUFA4: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 21, MIM#619065, Leigh syndrome, Complex IV deficiency
Mendeliome v0.5128 COX5A Zornitza Stark Phenotypes for gene: COX5A were changed from pulmonary arterial hypertension; lactic acidemia; failure to thrive; isolated complex IV deficiency to Mitochondrial complex IV deficiency, nuclear type 20, MIM#619064; pulmonary arterial hypertension; lactic acidemia; failure to thrive; isolated complex IV deficiency
Mendeliome v0.5127 COX5A Zornitza Stark edited their review of gene: COX5A: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 20, MIM#619064, pulmonary arterial hypertension, lactic acidemia, failure to thrive, isolated complex IV deficiency
Mitochondrial disease v0.547 COX5A Zornitza Stark Phenotypes for gene: COX5A were changed from pulmonary arterial hypertension; lactic acidemia; failure to thrive; isolated complex IV deficiency to Mitochondrial complex IV deficiency, nuclear type 20, MIM#619064; pulmonary arterial hypertension; lactic acidemia; failure to thrive; isolated complex IV deficiency
Mitochondrial disease v0.546 COX5A Zornitza Stark reviewed gene: COX5A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 20, MIM#619064; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5127 PET117 Zornitza Stark Phenotypes for gene: PET117 were changed from Developmental delay; Regression; Complex IV deficiency to Mitochondrial complex IV deficiency, nuclear type 19, MIM#619063; Developmental delay; Regression; Complex IV deficiency
Mendeliome v0.5126 PET117 Zornitza Stark edited their review of gene: PET117: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 19, MIM#619063, Developmental delay, Regression, Complex IV deficiency
Mitochondrial disease v0.546 PET117 Zornitza Stark Phenotypes for gene: PET117 were changed from Developmental delay to Mitochondrial complex IV deficiency, nuclear type 19, MIM#619063; Developmental delay
Mitochondrial disease v0.545 PET117 Zornitza Stark reviewed gene: PET117: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 19, MIM#619063; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5126 COX6A2 Zornitza Stark Phenotypes for gene: COX6A2 were changed from Mitochondrial complex IV deficiency, MIM# 220110 to Mitochondrial complex IV deficiency, nuclear type 18, MIM#619062
Mendeliome v0.5125 COX6A2 Zornitza Stark edited their review of gene: COX6A2: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 18, MIM#619062
Mitochondrial disease v0.545 COX6A2 Zornitza Stark Phenotypes for gene: COX6A2 were changed from Mitochondrial complex IV deficiency, MIM# 220110 to Mitochondrial complex IV deficiency, nuclear type 18, MIM#619062
Mitochondrial disease v0.544 COX6A2 Zornitza Stark edited their review of gene: COX6A2: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 18, MIM#619062
Intellectual disability syndromic and non-syndromic v0.3118 APOPT1 Zornitza Stark Marked gene: APOPT1 as ready
Intellectual disability syndromic and non-syndromic v0.3118 APOPT1 Zornitza Stark Gene: apopt1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3118 APOPT1 Zornitza Stark Phenotypes for gene: APOPT1 were changed from Mitochondrial complex IV deficiency, nuclear type 17, MIM#619061 to Mitochondrial complex IV deficiency, nuclear type 17, MIM#619061
Regression v0.198 APOPT1 Zornitza Stark Marked gene: APOPT1 as ready
Regression v0.198 APOPT1 Zornitza Stark Gene: apopt1 has been classified as Green List (High Evidence).
Regression v0.198 APOPT1 Zornitza Stark Classified gene: APOPT1 as Green List (high evidence)
Regression v0.198 APOPT1 Zornitza Stark Gene: apopt1 has been classified as Green List (High Evidence).
Regression v0.198 APOPT1 Zornitza Stark Classified gene: APOPT1 as Green List (high evidence)
Regression v0.198 APOPT1 Zornitza Stark Gene: apopt1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3117 APOPT1 Zornitza Stark Phenotypes for gene: APOPT1 were changed from to Mitochondrial complex IV deficiency, nuclear type 17, MIM#619061
Regression v0.197 APOPT1 Zornitza Stark gene: APOPT1 was added
gene: APOPT1 was added to Regression. Sources: Expert list
Mode of inheritance for gene: APOPT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: APOPT1 were set to 25175347
Phenotypes for gene: APOPT1 were set to Mitochondrial complex IV deficiency, nuclear type 17, MIM#619061
Review for gene: APOPT1 was set to GREEN
Added comment: 6 individuals from 5 unrelated families reported, presenting in late infancy or early childhood with evidence of complex IV deficiency. Phenotype varied widely. Five individuals had episodes of neurologic regression manifest as gait difficulties and spastic tetraparesis, sensorimotor polyneuropathy, and dysarthria that in some cases improved over time. The sixth individual never developed neurologic signs. Three had normal cognition and 3 had impaired cognition. Brain imaging showed a cavitating leukodystrophy, predominantly affecting the posterior cerebral white matter and corpus callosum, that stabilized or even improved over time.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.3116 APOPT1 Zornitza Stark Publications for gene: APOPT1 were set to
Intellectual disability syndromic and non-syndromic v0.3115 APOPT1 Zornitza Stark Mode of inheritance for gene: APOPT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3114 APOPT1 Zornitza Stark reviewed gene: APOPT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25175347; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 17, MIM#619061; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.544 APOPT1 Zornitza Stark Marked gene: APOPT1 as ready
Mitochondrial disease v0.544 APOPT1 Zornitza Stark Gene: apopt1 has been classified as Green List (High Evidence).
Mendeliome v0.5125 APOPT1 Zornitza Stark Marked gene: APOPT1 as ready
Mendeliome v0.5125 APOPT1 Zornitza Stark Gene: apopt1 has been classified as Green List (High Evidence).
Mitochondrial disease v0.544 APOPT1 Zornitza Stark Phenotypes for gene: APOPT1 were changed from to Mitochondrial complex IV deficiency, nuclear type 17, MIM#619061
Mendeliome v0.5125 APOPT1 Zornitza Stark Phenotypes for gene: APOPT1 were changed from to Mitochondrial complex IV deficiency, nuclear type 17, MIM#619061
Mendeliome v0.5124 APOPT1 Zornitza Stark Publications for gene: APOPT1 were set to
Mitochondrial disease v0.543 APOPT1 Zornitza Stark Publications for gene: APOPT1 were set to 25175347
Mitochondrial disease v0.542 APOPT1 Zornitza Stark Publications for gene: APOPT1 were set to 25175347]
Mendeliome v0.5123 APOPT1 Zornitza Stark Mode of inheritance for gene: APOPT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.542 APOPT1 Zornitza Stark Publications for gene: APOPT1 were set to 25175347]
Mendeliome v0.5122 APOPT1 Zornitza Stark reviewed gene: APOPT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25175347]; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 17, MIM#619061; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.541 APOPT1 Zornitza Stark Publications for gene: APOPT1 were set to
Mitochondrial disease v0.540 APOPT1 Zornitza Stark Mode of inheritance for gene: APOPT1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.540 APOPT1 Zornitza Stark Mode of inheritance for gene: APOPT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.539 APOPT1 Zornitza Stark reviewed gene: APOPT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25175347]; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 17, MIM#619061; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Regression v0.196 COX4I1 Zornitza Stark Marked gene: COX4I1 as ready
Regression v0.196 COX4I1 Zornitza Stark Gene: cox4i1 has been classified as Amber List (Moderate Evidence).
Regression v0.196 COX4I1 Zornitza Stark Classified gene: COX4I1 as Amber List (moderate evidence)
Regression v0.196 COX4I1 Zornitza Stark Gene: cox4i1 has been classified as Amber List (Moderate Evidence).
Regression v0.195 COX4I1 Zornitza Stark gene: COX4I1 was added
gene: COX4I1 was added to Regression. Sources: Expert list
Mode of inheritance for gene: COX4I1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COX4I1 were set to 28766551; 22592081; 31290619
Phenotypes for gene: COX4I1 were set to Mitochondrial complex IV deficiency, nuclear type 16, MIM#619060
Review for gene: COX4I1 was set to AMBER
Added comment: Two unrelated families reported, regression was a feature in both.
Sources: Expert list
Mendeliome v0.5122 COX4I1 Zornitza Stark Marked gene: COX4I1 as ready
Mendeliome v0.5122 COX4I1 Zornitza Stark Gene: cox4i1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5122 COX4I1 Zornitza Stark Classified gene: COX4I1 as Amber List (moderate evidence)
Mendeliome v0.5122 COX4I1 Zornitza Stark Gene: cox4i1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5121 COX4I1 Zornitza Stark gene: COX4I1 was added
gene: COX4I1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: COX4I1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COX4I1 were set to 28766551; 22592081; 31290619
Phenotypes for gene: COX4I1 were set to Mitochondrial complex IV deficiency, nuclear type 16, MIM#619060
Review for gene: COX4I1 was set to AMBER
Added comment: Two unrelated families reported.

Two more variants reported in PMID: 22592081: one is non-coding and the other rare missense, appear to have been identified in separate individuals, i.e. heterozygous in each individual.
Sources: Expert list
Mitochondrial disease v0.539 COX4I1 Zornitza Stark Phenotypes for gene: COX4I1 were changed from short stature; mild dysmorphic features; Fanconi anemia to Mitochondrial complex IV deficiency, nuclear type 16, MIM#619060; regression; seizures; short stature; mild dysmorphic features; Fanconi anemia
Mitochondrial disease v0.538 COX4I1 Zornitza Stark Publications for gene: COX4I1 were set to 28766551; 22592081
Mitochondrial disease v0.537 COX4I1 Zornitza Stark Classified gene: COX4I1 as Amber List (moderate evidence)
Mitochondrial disease v0.537 COX4I1 Zornitza Stark Gene: cox4i1 has been classified as Amber List (Moderate Evidence).
Mitochondrial disease v0.536 COX4I1 Zornitza Stark edited their review of gene: COX4I1: Added comment: Further family with two affected sibs reported in PMID 31290619, upgrade to Amber.; Changed rating: AMBER; Changed publications: 28766551, 22592081, 31290619; Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 16, MIM#619060
Mendeliome v0.5120 COX8A Zornitza Stark Phenotypes for gene: COX8A were changed from Mitochondrial complex IV deficiency, MIM# 220110 to Mitochondrial complex IV deficiency, nuclear type 15, MIM#619059
Mendeliome v0.5119 COX8A Zornitza Stark edited their review of gene: COX8A: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 15, MIM#619059
Mitochondrial disease v0.536 COX8A Zornitza Stark Phenotypes for gene: COX8A were changed from Mitochondrial complex IV deficiency, MIM# 220110 to Mitochondrial complex IV deficiency, nuclear type 15, MIM#619059
Mitochondrial disease v0.535 COX8A Zornitza Stark edited their review of gene: COX8A: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 15, MIM#619059
Intellectual disability syndromic and non-syndromic v0.3114 COA3 Zornitza Stark Phenotypes for gene: COA3 were changed from Mitochondrial complex IV deficiency to Mitochondrial complex IV deficiency, nuclear type 14, MIM# 619058
Intellectual disability syndromic and non-syndromic v0.3113 COA3 Zornitza Stark edited their review of gene: COA3: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 14, MIM# 619058
Mendeliome v0.5119 COA3 Zornitza Stark Phenotypes for gene: COA3 were changed from Mitochondrial complex IV deficiency to Mitochondrial complex IV deficiency, nuclear type 14, MIM# 619058
Mendeliome v0.5118 COA3 Zornitza Stark edited their review of gene: COA3: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 14, MIM# 619058
Mitochondrial disease v0.535 COA3 Zornitza Stark Phenotypes for gene: COA3 were changed from Mitochondrial complex IV deficiency to Mitochondrial complex IV deficiency, nuclear type 14, MIM#619058
Mitochondrial disease v0.534 COA3 Zornitza Stark edited their review of gene: COA3: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 14, MIM# 619058
Regression v0.194 PET100 Zornitza Stark Marked gene: PET100 as ready
Regression v0.194 PET100 Zornitza Stark Gene: pet100 has been classified as Red List (Low Evidence).
Regression v0.194 PET100 Zornitza Stark Phenotypes for gene: PET100 were changed from to Mitochondrial complex IV deficiency, nuclear type 12, MIM# 619055
Regression v0.193 PET100 Zornitza Stark Publications for gene: PET100 were set to 24462369; 25293719; 31406627
Regression v0.193 PET100 Zornitza Stark Publications for gene: PET100 were set to
Regression v0.192 PET100 Zornitza Stark Mode of inheritance for gene: PET100 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Regression v0.191 PET100 Zornitza Stark Classified gene: PET100 as Red List (low evidence)
Regression v0.191 PET100 Zornitza Stark Gene: pet100 has been classified as Red List (Low Evidence).
Regression v0.190 PET100 Zornitza Stark reviewed gene: PET100: Rating: RED; Mode of pathogenicity: None; Publications: 24462369, 25293719, 31406627; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 12, MIM# 619055; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.893 PET100 Zornitza Stark Marked gene: PET100 as ready
Genetic Epilepsy v0.893 PET100 Zornitza Stark Gene: pet100 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.893 PET100 Zornitza Stark Phenotypes for gene: PET100 were changed from to Mitochondrial complex IV deficiency, nuclear type 12, MIM# 619055
Genetic Epilepsy v0.892 PET100 Zornitza Stark Publications for gene: PET100 were set to
Genetic Epilepsy v0.891 PET100 Zornitza Stark Mode of inheritance for gene: PET100 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.890 PET100 Zornitza Stark Tag founder tag was added to gene: PET100.
Genetic Epilepsy v0.890 PET100 Zornitza Stark reviewed gene: PET100: Rating: GREEN; Mode of pathogenicity: None; Publications: 24462369, 25293719, 31406627; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 12, MIM# 619055; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3113 PET100 Zornitza Stark Phenotypes for gene: PET100 were changed from Mitochondrial complex IV deficiency, MIM# 220110 to Mitochondrial complex IV deficiency, nuclear type 12, MIM# 619055
Intellectual disability syndromic and non-syndromic v0.3112 PET100 Zornitza Stark Tag founder tag was added to gene: PET100.
Intellectual disability syndromic and non-syndromic v0.3112 PET100 Zornitza Stark edited their review of gene: PET100: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 12, MIM# 619055
Mendeliome v0.5118 PET100 Zornitza Stark Marked gene: PET100 as ready
Mendeliome v0.5118 PET100 Zornitza Stark Gene: pet100 has been classified as Green List (High Evidence).
Mendeliome v0.5118 PET100 Zornitza Stark Phenotypes for gene: PET100 were changed from to Mitochondrial complex IV deficiency, nuclear type 12, MIM# 619055
Mendeliome v0.5117 PET100 Zornitza Stark Publications for gene: PET100 were set to
Mendeliome v0.5116 PET100 Zornitza Stark Mode of inheritance for gene: PET100 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5115 PET100 Zornitza Stark Tag founder tag was added to gene: PET100.
Mendeliome v0.5115 PET100 Zornitza Stark reviewed gene: PET100: Rating: GREEN; Mode of pathogenicity: None; Publications: 24462369, 25293719, 31406627; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 12, MIM# 619055; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.534 PET100 Zornitza Stark Marked gene: PET100 as ready
Mitochondrial disease v0.534 PET100 Zornitza Stark Gene: pet100 has been classified as Green List (High Evidence).
Mitochondrial disease v0.534 PET100 Zornitza Stark Phenotypes for gene: PET100 were changed from to Mitochondrial complex IV deficiency, nuclear type 12, MIM# 619055
Mitochondrial disease v0.533 PET100 Zornitza Stark Publications for gene: PET100 were set to
Mitochondrial disease v0.532 PET100 Zornitza Stark Mode of inheritance for gene: PET100 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.531 PET100 Zornitza Stark Tag founder tag was added to gene: PET100.
Mitochondrial disease v0.531 PET100 Zornitza Stark reviewed gene: PET100: Rating: GREEN; Mode of pathogenicity: None; Publications: 24462369, 25293719, 31406627; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 12, MIM# 619055; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5115 COX20 Zornitza Stark Marked gene: COX20 as ready
Mendeliome v0.5115 COX20 Zornitza Stark Gene: cox20 has been classified as Green List (High Evidence).
Mendeliome v0.5115 COX20 Zornitza Stark Phenotypes for gene: COX20 were changed from to Mitochondrial complex IV deficiency, nuclear type 11, MIM#619054
Mendeliome v0.5114 COX20 Zornitza Stark Publications for gene: COX20 were set to
Mendeliome v0.5113 COX20 Zornitza Stark Mode of inheritance for gene: COX20 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5112 COX20 Zornitza Stark reviewed gene: COX20: Rating: GREEN; Mode of pathogenicity: None; Publications: 24202787, 31079202, 30656193, 23125284, 32606554; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 11, MIM#619054; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.531 COX20 Zornitza Stark Marked gene: COX20 as ready
Mitochondrial disease v0.531 COX20 Zornitza Stark Gene: cox20 has been classified as Green List (High Evidence).
Mitochondrial disease v0.531 COX20 Zornitza Stark Phenotypes for gene: COX20 were changed from to Mitochondrial complex IV deficiency, nuclear type 11, MIM#619054
Mitochondrial disease v0.530 COX20 Zornitza Stark Publications for gene: COX20 were set to
Mitochondrial disease v0.529 COX20 Zornitza Stark Mode of inheritance for gene: COX20 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.528 COX20 Zornitza Stark reviewed gene: COX20: Rating: GREEN; Mode of pathogenicity: None; Publications: 24202787, 31079202, 30656193, 23125284, 32606554; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 11, MIM#619054; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v0.35 COX14 Zornitza Stark Marked gene: COX14 as ready
Cardiomyopathy_Paediatric v0.35 COX14 Zornitza Stark Gene: cox14 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v0.35 COX14 Zornitza Stark Phenotypes for gene: COX14 were changed from ?Mitochondrial complex IV deficiency, 220110 to Mitochondrial complex IV deficiency, nuclear type 10, MIM# 619053
Cardiomyopathy_Paediatric v0.34 COX14 Zornitza Stark Publications for gene: COX14 were set to
Cardiomyopathy_Paediatric v0.33 COX14 Zornitza Stark Classified gene: COX14 as Amber List (moderate evidence)
Cardiomyopathy_Paediatric v0.33 COX14 Zornitza Stark Gene: cox14 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v0.32 COX14 Zornitza Stark reviewed gene: COX14: Rating: AMBER; Mode of pathogenicity: None; Publications: 22243966; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 10, MIM# 619053; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3112 COX14 Zornitza Stark Phenotypes for gene: COX14 were changed from Mitochondrial complex IV deficiency, MIM#220110 to Mitochondrial complex IV deficiency, nuclear type 10, MIM#619053
Intellectual disability syndromic and non-syndromic v0.3111 COX14 Zornitza Stark edited their review of gene: COX14: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 10, MIM#619053
Regression v0.190 COX14 Zornitza Stark Phenotypes for gene: COX14 were changed from Mitochondrial complex IV deficiency, MIM#220110 to Mitochondrial complex IV deficiency, nuclear type 10, MIM#619053
Regression v0.189 COX14 Zornitza Stark edited their review of gene: COX14: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 10, MIM#619053
Mendeliome v0.5112 COX14 Zornitza Stark Phenotypes for gene: COX14 were changed from Mitochondrial complex IV deficiency, MIM#220110 to Mitochondrial complex IV deficiency, nuclear type 10, MIM#619053
Mendeliome v0.5111 COX14 Zornitza Stark edited their review of gene: COX14: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 10, MIM#619053
Mitochondrial disease v0.528 COX14 Zornitza Stark Phenotypes for gene: COX14 were changed from Mitochondrial complex IV deficiency, MIM#220110 to Mitochondrial complex IV deficiency, nuclear type 10, MIM# 619053
Mitochondrial disease v0.527 COX14 Zornitza Stark edited their review of gene: COX14: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 10, MIM# 619053
Regression v0.189 TACO1 Zornitza Stark Marked gene: TACO1 as ready
Regression v0.189 TACO1 Zornitza Stark Gene: taco1 has been classified as Amber List (Moderate Evidence).
Regression v0.189 TACO1 Zornitza Stark Phenotypes for gene: TACO1 were changed from to Mitochondrial complex IV deficiency, nuclear type 8, MIM# 619052
Regression v0.188 TACO1 Zornitza Stark Publications for gene: TACO1 were set to
Regression v0.187 TACO1 Zornitza Stark Mode of inheritance for gene: TACO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Regression v0.186 TACO1 Zornitza Stark Classified gene: TACO1 as Amber List (moderate evidence)
Regression v0.186 TACO1 Zornitza Stark Gene: taco1 has been classified as Amber List (Moderate Evidence).
Regression v0.185 TACO1 Zornitza Stark reviewed gene: TACO1: Rating: AMBER; Mode of pathogenicity: None; Publications: 19503089, 20727754, 25044680, 27319982; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 8, MIM# 619052; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5111 TACO1 Zornitza Stark Marked gene: TACO1 as ready
Mendeliome v0.5111 TACO1 Zornitza Stark Gene: taco1 has been classified as Green List (High Evidence).
Mendeliome v0.5111 TACO1 Zornitza Stark Phenotypes for gene: TACO1 were changed from to Mitochondrial complex IV deficiency, nuclear type 8, MIM# 619052
Mendeliome v0.5110 TACO1 Zornitza Stark Publications for gene: TACO1 were set to
Mendeliome v0.5109 TACO1 Zornitza Stark Mode of inheritance for gene: TACO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5108 TACO1 Zornitza Stark reviewed gene: TACO1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19503089, 20727754, 25044680, 27319982; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 8, MIM# 619052; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.527 TACO1 Zornitza Stark Phenotypes for gene: TACO1 were changed from Mitochondrial complex IV deficiency; OMIM #220110 to Mitochondrial complex IV deficiency, nuclear type 8, MIM# 619052
Mitochondrial disease v0.526 TACO1 Zornitza Stark edited their review of gene: TACO1: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 8, MIM# 619052
Ciliopathies v0.217 PRKACA Zornitza Stark Marked gene: PRKACA as ready
Ciliopathies v0.217 PRKACA Zornitza Stark Gene: prkaca has been classified as Green List (High Evidence).
Ciliopathies v0.217 PRKACA Zornitza Stark Classified gene: PRKACA as Green List (high evidence)
Ciliopathies v0.217 PRKACA Zornitza Stark Gene: prkaca has been classified as Green List (High Evidence).
Ciliopathies v0.216 PRKACA Zornitza Stark gene: PRKACA was added
gene: PRKACA was added to Ciliopathies. Sources: Literature
Mode of inheritance for gene: PRKACA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PRKACA were set to 33058759; 31130284
Phenotypes for gene: PRKACA were set to Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability
Mode of pathogenicity for gene: PRKACA 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: PRKACA was set to GREEN
Added comment: Palencia-Campos et al (2020 - PMID: 33058759) report on the phenotype of 3 individuals heterozygous for PRKACA and 4 individuals heterozygous for PRKACB pathogenic variants.

Gene included in this panel due to significant overlap with ciliopathies.

The most characteristic features in all individuals with PRKACA/PRKACB mutation, included postaxial polydactyly of hands (6/7 bilateral, 1/7 unilateral) and feet (4/7 bilateral, 1/7 unilateral), brachydactyly and congenital heart defects (CHD 5/7) namely a common atrium or AVSD. Two individuals with PRKACA variant who did not have CHD had offspring with the same variant and an AVSD.

Other variably occurring features included short stature, limbs, narrow chest, abnormal teeth, oral frenula, nail dysplasia. One individual with PRKACB variant presented tumors.

Intellectual disability was reported in 2/4 individuals with PRKACB variant (1/4: mild, 1/4: severe). The 3 individuals with PRKACA variant did not present ID.

As the phenotype was overall suggestive of Ellis-van Creveld syndrome (or the allelic Weyers acrofacial dysostosis), although these diagnoses were ruled out following analysis of EVC and EVC2 genes.

WES was carried out in all.

PRKACA : A single heterozygous missense variant was identified in 3 individuals from 3 families (NM_002730.4:c.409G>A / p.Gly137Arg) with 1 of the probands harboring the variant in mosaic state (28% of reads) and having 2 similarly affected offspring. The variant was de novo in one individual and inherited in a third one having a similarly affected fetus (narrow thorax, postaxial polyd, AVSD).

PRKACB : 4 different variants were identified (NM_002731.3: p.His88Arg/Asn, p.Gly235Arg, c.161C>T - p.Ser54Leu). One of the individuals was mosaic for the latter variant, while in all other cases the variant had occurred de novo.

Protein kinase A (PKA) is a tetrameric holoenzyme formed by the association of 2 catalytic (C) subunits with a regulatory (R) subunit dimer. Activation of PKA is achieved through binding of 2 cAMP molecules to each R-subunit, and unleashing(/dissociation) of C-subunits to engage substrates. PRKACA/B genes encode the Cα- and Cβ-subunits while the 4 functionally non-redundant regulatory subunits are encoded by PRKAR1A/1B/2A/2B genes.

The authors provide evidence that the variants confer increased sensitivity of PKA holoenzymes to activation by cAMP (compared to wt).

By performing ectopic expression of wt or mt PRKACA/B (variants studied : PRKACA p.Gly137Arg / PRKACB p.Gly235Arg) in NIH 3T3 fibroblasts, the authors demonstrate that inhibition of hedgehog signaling likely underlyies the developmental defects observed in affected individuals.

As for PRKACA, the authors cite another study where a 31-month old female with EvC syndrome diagnosis was found to harbor the aforementioned variant (NM_001304349.1:c.637G>A:p.Gly213Arg corresponding to NM_002730.4:c.409G>A / p.Gly137Arg) as a de novo event. Without additional evidence at the time, the variant was considered to be a candidate for this subject's phenotype (Monies et al 2019 – PMID: 31130284).
Sources: Literature
Polydactyly v0.182 PRKACA Zornitza Stark Classified gene: PRKACA as Green List (high evidence)
Polydactyly v0.182 PRKACA Zornitza Stark Gene: prkaca has been classified as Green List (High Evidence).
Congenital Heart Defect v0.80 PRKACA Zornitza Stark Marked gene: PRKACA as ready
Congenital Heart Defect v0.80 PRKACA Zornitza Stark Gene: prkaca has been classified as Green List (High Evidence).
Congenital Heart Defect v0.80 PRKACA Zornitza Stark Classified gene: PRKACA as Green List (high evidence)
Congenital Heart Defect v0.80 PRKACA Zornitza Stark Gene: prkaca has been classified as Green List (High Evidence).
Mendeliome v0.5108 PRKACA Zornitza Stark Marked gene: PRKACA as ready
Mendeliome v0.5108 PRKACA Zornitza Stark Gene: prkaca has been classified as Green List (High Evidence).
Mendeliome v0.5108 PRKACA Zornitza Stark Classified gene: PRKACA as Green List (high evidence)
Mendeliome v0.5108 PRKACA Zornitza Stark Gene: prkaca has been classified as Green List (High Evidence).
Ciliopathies v0.215 PRKACB Zornitza Stark Marked gene: PRKACB as ready
Ciliopathies v0.215 PRKACB Zornitza Stark Gene: prkacb has been classified as Green List (High Evidence).
Ciliopathies v0.215 PRKACB Zornitza Stark Classified gene: PRKACB as Green List (high evidence)
Ciliopathies v0.215 PRKACB Zornitza Stark Gene: prkacb has been classified as Green List (High Evidence).
Ciliopathies v0.214 PRKACB Zornitza Stark gene: PRKACB was added
gene: PRKACB was added to Ciliopathies. Sources: Literature
Mode of inheritance for gene: PRKACB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PRKACB were set to 33058759
Phenotypes for gene: PRKACB were set to Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability
Mode of pathogenicity for gene: PRKACB 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: PRKACB was set to GREEN
Added comment: Palencia-Campos et al (2020 - PMID: 33058759) report on the phenotype of 3 individuals heterozygous for PRKACA and 4 individuals heterozygous for PRKACB pathogenic variants.

Gene included in this panel due to significant phenotypic overlap with ciliopathies.

The most characteristic features in all individuals with PRKACA/PRKACB mutation, included postaxial polydactyly of hands (6/7 bilateral, 1/7 unilateral) and feet (4/7 bilateral, 1/7 unilateral), brachydactyly and congenital heart defects (CHD 5/7) namely a common atrium or AVSD. Two individuals with PRKACA variant who did not have CHD had offspring with the same variant and an AVSD.

Other variably occurring features included short stature, limbs, narrow chest, abnormal teeth, oral frenula, nail dysplasia. One individual with PRKACB variant presented tumors.

Intellectual disability was reported in 2/4 individuals with PRKACB variant (1/4: mild, 1/4: severe). The 3 individuals with PRKACA variant did not present ID.

As the phenotype was overall suggestive of Ellis-van Creveld syndrome (or the allelic Weyers acrofacial dysostosis), although these diagnoses were ruled out following analysis of EVC and EVC2 genes.

WES was carried out in all.

PRKACA : A single heterozygous missense variant was identified in 3 individuals from 3 families (NM_002730.4:c.409G>A / p.Gly137Arg) with 1 of the probands harboring the variant in mosaic state (28% of reads) and having 2 similarly affected offspring. The variant was de novo in one individual and inherited in a third one having a similarly affected fetus (narrow thorax, postaxial polyd, AVSD).

PRKACB : 4 different variants were identified (NM_002731.3: p.His88Arg/Asn, p.Gly235Arg, c.161C>T - p.Ser54Leu). One of the individuals was mosaic for the latter variant, while in all other cases the variant had occurred de novo.

Protein kinase A (PKA) is a tetrameric holoenzyme formed by the association of 2 catalytic (C) subunits with a regulatory (R) subunit dimer. Activation of PKA is achieved through binding of 2 cAMP molecules to each R-subunit, and unleashing(/dissociation) of C-subunits to engage substrates. PRKACA/B genes encode the Cα- and Cβ-subunits while the 4 functionally non-redundant regulatory subunits are encoded by PRKAR1A/1B/2A/2B genes.

The authors provide evidence that the variants confer increased sensitivity of PKA holoenzymes to activation by cAMP (compared to wt).

By performing ectopic expression of wt or mt PRKACA/B (variants studied : PRKACA p.Gly137Arg / PRKACB p.Gly235Arg) in NIH 3T3 fibroblasts, the authors demonstrate that inhibition of hedgehog signaling likely underlyies the developmental defects observed in affected individuals.

As for PRKACA, the authors cite another study where a 31-month old female with EvC syndrome diagnosis was found to harbor the aforementioned variant (NM_001304349.1:c.637G>A:p.Gly213Arg corresponding to NM_002730.4:c.409G>A / p.Gly137Arg) as a de novo event. Without additional evidence at the time, the variant was considered to be a candidate for this subject's phenotype (Monies et al 2019 – PMID: 31130284).
Sources: Literature
Mendeliome v0.5107 PRKACB Zornitza Stark Classified gene: PRKACB as Green List (high evidence)
Mendeliome v0.5107 PRKACB Zornitza Stark Gene: prkacb has been classified as Green List (High Evidence).
Congenital Heart Defect v0.79 PRKACB Zornitza Stark Marked gene: PRKACB as ready
Congenital Heart Defect v0.79 PRKACB Zornitza Stark Gene: prkacb has been classified as Green List (High Evidence).
Congenital Heart Defect v0.79 PRKACB Zornitza Stark Classified gene: PRKACB as Green List (high evidence)
Congenital Heart Defect v0.79 PRKACB Zornitza Stark Gene: prkacb has been classified as Green List (High Evidence).
Polydactyly v0.181 PRKACB Zornitza Stark Marked gene: PRKACB as ready
Polydactyly v0.181 PRKACB Zornitza Stark Gene: prkacb has been classified as Green List (High Evidence).
Polydactyly v0.181 PRKACB Zornitza Stark Classified gene: PRKACB as Green List (high evidence)
Polydactyly v0.181 PRKACB Zornitza Stark Gene: prkacb has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3111 PRKACB Zornitza Stark Marked gene: PRKACB as ready
Intellectual disability syndromic and non-syndromic v0.3111 PRKACB Zornitza Stark Gene: prkacb has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3111 PRKACB Zornitza Stark Classified gene: PRKACB as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3111 PRKACB Zornitza Stark Gene: prkacb has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5106 CNGA2 Zornitza Stark Marked gene: CNGA2 as ready
Mendeliome v0.5106 CNGA2 Zornitza Stark Gene: cnga2 has been classified as Red List (Low Evidence).
Mendeliome v0.5106 CNGA2 Zornitza Stark gene: CNGA2 was added
gene: CNGA2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CNGA2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: CNGA2 were set to 28572688
Phenotypes for gene: CNGA2 were set to Congenital anosmia
Review for gene: CNGA2 was set to RED
Added comment: Single multiplex family with high-impact variant segregating with anosmia.
Sources: Literature
Cardiomyopathy_Paediatric v0.32 COX6B1 Zornitza Stark Marked gene: COX6B1 as ready
Cardiomyopathy_Paediatric v0.32 COX6B1 Zornitza Stark Gene: cox6b1 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v0.32 COX6B1 Zornitza Stark Phenotypes for gene: COX6B1 were changed from Mitochondrial complex IV deficiency, 220110 to Mitochondrial complex IV deficiency, nuclear type 7, MIM# 619051
Cardiomyopathy_Paediatric v0.31 COX6B1 Zornitza Stark Publications for gene: COX6B1 were set to
Cardiomyopathy_Paediatric v0.30 COX6B1 Zornitza Stark Classified gene: COX6B1 as Amber List (moderate evidence)
Cardiomyopathy_Paediatric v0.30 COX6B1 Zornitza Stark Gene: cox6b1 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v0.29 COX6B1 Zornitza Stark reviewed gene: COX6B1: Rating: AMBER; Mode of pathogenicity: None; Publications: 18499082, 24781756; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 7, MIM# 619051; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3110 COX6B1 Zornitza Stark Marked gene: COX6B1 as ready
Intellectual disability syndromic and non-syndromic v0.3110 COX6B1 Zornitza Stark Gene: cox6b1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.3110 COX6B1 Zornitza Stark Phenotypes for gene: COX6B1 were changed from to Mitochondrial complex IV deficiency, nuclear type 7, MIM# 619051
Intellectual disability syndromic and non-syndromic v0.3109 COX6B1 Zornitza Stark Publications for gene: COX6B1 were set to
Intellectual disability syndromic and non-syndromic v0.3108 COX6B1 Zornitza Stark Mode of inheritance for gene: COX6B1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3107 COX6B1 Zornitza Stark Classified gene: COX6B1 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.3107 COX6B1 Zornitza Stark Gene: cox6b1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.3106 COX6B1 Zornitza Stark reviewed gene: COX6B1: Rating: RED; Mode of pathogenicity: None; Publications: 18499082, 24781756; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 7, MIM# 619051; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Regression v0.185 COX6B1 Zornitza Stark Marked gene: COX6B1 as ready
Regression v0.185 COX6B1 Zornitza Stark Gene: cox6b1 has been classified as Amber List (Moderate Evidence).
Regression v0.185 COX6B1 Zornitza Stark Phenotypes for gene: COX6B1 were changed from to Mitochondrial complex IV deficiency, nuclear type 7, MIM# 619051
Regression v0.184 COX6B1 Zornitza Stark Publications for gene: COX6B1 were set to
Regression v0.183 COX6B1 Zornitza Stark Mode of inheritance for gene: COX6B1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Regression v0.182 COX6B1 Zornitza Stark Classified gene: COX6B1 as Amber List (moderate evidence)
Regression v0.182 COX6B1 Zornitza Stark Gene: cox6b1 has been classified as Amber List (Moderate Evidence).
Regression v0.181 COX6B1 Zornitza Stark reviewed gene: COX6B1: Rating: AMBER; Mode of pathogenicity: None; Publications: 18499082, 24781756; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 7, MIM# 619051; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5105 COX6B1 Zornitza Stark Marked gene: COX6B1 as ready
Mendeliome v0.5105 COX6B1 Zornitza Stark Gene: cox6b1 has been classified as Green List (High Evidence).
Mendeliome v0.5105 COX6B1 Zornitza Stark Phenotypes for gene: COX6B1 were changed from to Mitochondrial complex IV deficiency, nuclear type 7, MIM# 619051
Mendeliome v0.5104 COX6B1 Zornitza Stark Publications for gene: COX6B1 were set to
Mendeliome v0.5103 COX6B1 Zornitza Stark Mode of inheritance for gene: COX6B1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5102 COX6B1 Zornitza Stark reviewed gene: COX6B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 18499082, 24781756; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 7, MIM# 619051; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.526 COX6B1 Zornitza Stark Marked gene: COX6B1 as ready
Mitochondrial disease v0.526 COX6B1 Zornitza Stark Gene: cox6b1 has been classified as Green List (High Evidence).
Mitochondrial disease v0.526 COX6B1 Zornitza Stark Phenotypes for gene: COX6B1 were changed from to Mitochondrial complex IV deficiency, nuclear type 7, MIM# 619051
Mitochondrial disease v0.525 COX6B1 Zornitza Stark Publications for gene: COX6B1 were set to
Regression v0.181 SHANK3 Zornitza Stark Marked gene: SHANK3 as ready
Regression v0.181 SHANK3 Zornitza Stark Gene: shank3 has been classified as Green List (High Evidence).
Regression v0.181 SHANK3 Zornitza Stark Classified gene: SHANK3 as Green List (high evidence)
Regression v0.181 SHANK3 Zornitza Stark Gene: shank3 has been classified as Green List (High Evidence).
Mitochondrial disease v0.524 COX6B1 Zornitza Stark Mode of inheritance for gene: COX6B1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.523 COX6B1 Zornitza Stark reviewed gene: COX6B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 18499082, 24781756; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 7, MIM# 619051; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.890 SCO1 Zornitza Stark Marked gene: SCO1 as ready
Genetic Epilepsy v0.890 SCO1 Zornitza Stark Gene: sco1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.890 SCO1 Zornitza Stark Phenotypes for gene: SCO1 were changed from to Mitochondrial complex IV deficiency, nuclear type 4, MIM# 619048
Genetic Epilepsy v0.889 SCO1 Zornitza Stark Publications for gene: SCO1 were set to
Genetic Epilepsy v0.888 SCO1 Zornitza Stark Mode of inheritance for gene: SCO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.887 SCO1 Zornitza Stark Classified gene: SCO1 as Amber List (moderate evidence)
Genetic Epilepsy v0.887 SCO1 Zornitza Stark Gene: sco1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.886 SCO1 Zornitza Stark reviewed gene: SCO1: Rating: AMBER; Mode of pathogenicity: None; Publications: 11013136, 19295170, 31352446, 23878101; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 4, MIM# 619048; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v0.29 SCO1 Zornitza Stark Classified gene: SCO1 as Amber List (moderate evidence)
Cardiomyopathy_Paediatric v0.29 SCO1 Zornitza Stark Gene: sco1 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v0.28 SCO1 Zornitza Stark Marked gene: SCO1 as ready
Cardiomyopathy_Paediatric v0.28 SCO1 Zornitza Stark Gene: sco1 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.28 SCO1 Zornitza Stark Phenotypes for gene: SCO1 were changed from Mitochondrial complex IV deficiency, 220110 to Mitochondrial complex IV deficiency, nuclear type 4, MIM# 619048
Cardiomyopathy_Paediatric v0.27 SCO1 Zornitza Stark Publications for gene: SCO1 were set to
Cardiomyopathy_Paediatric v0.26 SCO1 Zornitza Stark reviewed gene: SCO1: Rating: AMBER; Mode of pathogenicity: None; Publications: 11013136, 19295170, 31352446, 23878101; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 4, MIM# 619048; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3106 SCO1 Zornitza Stark Marked gene: SCO1 as ready
Intellectual disability syndromic and non-syndromic v0.3106 SCO1 Zornitza Stark Gene: sco1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.3106 SCO1 Zornitza Stark Phenotypes for gene: SCO1 were changed from to Mitochondrial complex IV deficiency, nuclear type 4, MIM# 619048
Intellectual disability syndromic and non-syndromic v0.3105 SCO1 Zornitza Stark Publications for gene: SCO1 were set to
Intellectual disability syndromic and non-syndromic v0.3104 SCO1 Zornitza Stark Mode of inheritance for gene: SCO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3103 SCO1 Zornitza Stark Classified gene: SCO1 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.3103 SCO1 Zornitza Stark Gene: sco1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.3102 SCO1 Zornitza Stark reviewed gene: SCO1: Rating: RED; Mode of pathogenicity: None; Publications: 11013136, 19295170, 31352446, 23878101; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 4, MIM# 619048; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5102 PRKACB Konstantinos Varvagiannis gene: PRKACB was added
gene: PRKACB was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PRKACB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PRKACB were set to 33058759
Phenotypes for gene: PRKACB were set to Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability
Penetrance for gene: PRKACB were set to unknown
Mode of pathogenicity for gene: PRKACB 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: PRKACB was set to GREEN
Added comment: Palencia-Campos et al (2020 - PMID: 33058759) report on the phenotype of 3 individuals heterozygous for PRKACA and 4 individuals heterozygous for PRKACB pathogenic variants.

The most characteristic features in all individuals with PRKACA/PRKACB mutation, included postaxial polydactyly of hands (6/7 bilateral, 1/7 unilateral) and feet (4/7 bilateral, 1/7 unilateral), brachydactyly and congenital heart defects (CHD 5/7) namely a common atrium or AVSD. Two individuals with PRKACA variant who did not have CHD had offspring with the same variant and an AVSD.

Other variably occurring features included short stature, limbs, narrow chest, abnormal teeth, oral frenula, nail dysplasia. One individual with PRKACB variant presented tumors.

Intellectual disability was reported in 2/4 individuals with PRKACB variant (1/4: mild, 1/4: severe). The 3 individuals with PRKACA variant did not present ID.

As the phenotype was overall suggestive of Ellis-van Creveld syndrome (or the allelic Weyers acrofacial dysostosis), although these diagnoses were ruled out following analysis of EVC and EVC2 genes.

WES was carried out in all.

PRKACA : A single heterozygous missense variant was identified in 3 individuals from 3 families (NM_002730.4:c.409G>A / p.Gly137Arg) with 1 of the probands harboring the variant in mosaic state (28% of reads) and having 2 similarly affected offspring. The variant was de novo in one individual and inherited in a third one having a similarly affected fetus (narrow thorax, postaxial polyd, AVSD).

PRKACB : 4 different variants were identified (NM_002731.3: p.His88Arg/Asn, p.Gly235Arg, c.161C>T - p.Ser54Leu). One of the individuals was mosaic for the latter variant, while in all other cases the variant had occurred de novo.

Protein kinase A (PKA) is a tetrameric holoenzyme formed by the association of 2 catalytic (C) subunits with a regulatory (R) subunit dimer. Activation of PKA is achieved through binding of 2 cAMP molecules to each R-subunit, and unleashing(/dissociation) of C-subunits to engage substrates. PRKACA/B genes encode the Cα- and Cβ-subunits while the 4 functionally non-redundant regulatory subunits are encoded by PRKAR1A/1B/2A/2B genes.

The authors provide evidence that the variants confer increased sensitivity of PKA holoenzymes to activation by cAMP (compared to wt).

By performing ectopic expression of wt or mt PRKACA/B (variants studied : PRKACA p.Gly137Arg / PRKACB p.Gly235Arg) in NIH 3T3 fibroblasts, the authors demonstrate that inhibition of hedgehog signaling likely underlyies the developmental defects observed in affected individuals.

As for PRKACA, the authors cite another study where a 31-month old female with EvC syndrome diagnosis was found to harbor the aforementioned variant (NM_001304349.1:c.637G>A:p.Gly213Arg corresponding to NM_002730.4:c.409G>A / p.Gly137Arg) as a de novo event. Without additional evidence at the time, the variant was considered to be a candidate for this subject's phenotype (Monies et al 2019 – PMID: 31130284).
Sources: Literature
Mendeliome v0.5102 PRKACA Konstantinos Varvagiannis gene: PRKACA was added
gene: PRKACA was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PRKACA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PRKACA were set to 33058759; 31130284
Phenotypes for gene: PRKACA were set to Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability
Penetrance for gene: PRKACA were set to unknown
Mode of pathogenicity for gene: PRKACA 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: PRKACA was set to GREEN
Added comment: Palencia-Campos et al (2020 - PMID: 33058759) report on the phenotype of 3 individuals heterozygous for PRKACA and 4 individuals heterozygous for PRKACB pathogenic variants.

The most characteristic features in all individuals with PRKACA/PRKACB mutation, included postaxial polydactyly of hands (6/7 bilateral, 1/7 unilateral) and feet (4/7 bilateral, 1/7 unilateral), brachydactyly and congenital heart defects (CHD 5/7) namely a common atrium or AVSD. Two individuals with PRKACA variant who did not have CHD had offspring with the same variant and an AVSD.

Other variably occurring features included short stature, limbs, narrow chest, abnormal teeth, oral frenula, nail dysplasia. One individual with PRKACB variant presented tumors.

Intellectual disability was reported in 2/4 individuals with PRKACB variant (1/4: mild, 1/4: severe). The 3 individuals with PRKACA variant did not present ID.

As the phenotype was overall suggestive of Ellis-van Creveld syndrome (or the allelic Weyers acrofacial dysostosis), although these diagnoses were ruled out following analysis of EVC and EVC2 genes.

WES was carried out in all.

PRKACA : A single heterozygous missense variant was identified in 3 individuals from 3 families (NM_002730.4:c.409G>A / p.Gly137Arg) with 1 of the probands harboring the variant in mosaic state (28% of reads) and having 2 similarly affected offspring. The variant was de novo in one individual and inherited in a third one having a similarly affected fetus (narrow thorax, postaxial polyd, AVSD).

PRKACB : 4 different variants were identified (NM_002731.3: p.His88Arg/Asn, p.Gly235Arg, c.161C>T - p.Ser54Leu). One of the individuals was mosaic for the latter variant, while in all other cases the variant had occurred de novo.

Protein kinase A (PKA) is a tetrameric holoenzyme formed by the association of 2 catalytic (C) subunits with a regulatory (R) subunit dimer. Activation of PKA is achieved through binding of 2 cAMP molecules to each R-subunit, and unleashing(/dissociation) of C-subunits to engage substrates. PRKACA/B genes encode the Cα- and Cβ-subunits while the 4 functionally non-redundant regulatory subunits are encoded by PRKAR1A/1B/2A/2B genes.

The authors provide evidence that the variants confer increased sensitivity of PKA holoenzymes to activation by cAMP (compared to wt).

By performing ectopic expression of wt or mt PRKACA/B (variants studied : PRKACA p.Gly137Arg / PRKACB p.Gly235Arg) in NIH 3T3 fibroblasts, the authors demonstrate that inhibition of hedgehog signaling likely underlyies the developmental defects observed in affected individuals.

As for PRKACA, the authors cite another study where a 31-month old female with EvC syndrome diagnosis was found to harbor the aforementioned variant (NM_001304349.1:c.637G>A:p.Gly213Arg corresponding to NM_002730.4:c.409G>A / p.Gly137Arg) as a de novo event. Without additional evidence at the time, the variant was considered to be a candidate for this subject's phenotype (Monies et al 2019 – PMID: 31130284).
Sources: Literature
Polydactyly v0.180 PRKACA Konstantinos Varvagiannis commented on gene: PRKACA: [ Please note that PRKACA / PRKACB may be considered in the differential diagnosis of several ciliopathies (polydactyly, narrow chest, heart defects) ]
Polydactyly v0.180 PRKACB Konstantinos Varvagiannis commented on gene: PRKACB: [ Please note that PRKACA / PRKACB may be considered in the differential diagnosis of several ciliopathies (polydactyly, narrow chest, heart defects) ]
Congenital Heart Defect v0.78 PRKACA Konstantinos Varvagiannis gene: PRKACA was added
gene: PRKACA was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: PRKACA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PRKACA were set to 33058759; 31130284
Phenotypes for gene: PRKACA were set to Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability
Penetrance for gene: PRKACA were set to unknown
Mode of pathogenicity for gene: PRKACA 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: PRKACA was set to GREEN
Added comment: Palencia-Campos et al (2020 - PMID: 33058759) report on the phenotype of 3 individuals heterozygous for PRKACA and 4 individuals heterozygous for PRKACB pathogenic variants.

The most characteristic features in all individuals with PRKACA/PRKACB mutation, included postaxial polydactyly of hands (6/7 bilateral, 1/7 unilateral) and feet (4/7 bilateral, 1/7 unilateral), brachydactyly and congenital heart defects (CHD 5/7) namely a common atrium or AVSD. Two individuals with PRKACA variant who did not have CHD had offspring with the same variant and an AVSD.

Other variably occurring features included short stature, limbs, narrow chest, abnormal teeth, oral frenula, nail dysplasia. One individual with PRKACB variant presented tumors.

Intellectual disability was reported in 2/4 individuals with PRKACB variant (1/4: mild, 1/4: severe). The 3 individuals with PRKACA variant did not present ID.

As the phenotype was overall suggestive of Ellis-van Creveld syndrome (or the allelic Weyers acrofacial dysostosis), although these diagnoses were ruled out following analysis of EVC and EVC2 genes.

WES was carried out in all.

PRKACA : A single heterozygous missense variant was identified in 3 individuals from 3 families (NM_002730.4:c.409G>A / p.Gly137Arg) with 1 of the probands harboring the variant in mosaic state (28% of reads) and having 2 similarly affected offspring. The variant was de novo in one individual and inherited in a third one having a similarly affected fetus (narrow thorax, postaxial polyd, AVSD).

PRKACB : 4 different variants were identified (NM_002731.3: p.His88Arg/Asn, p.Gly235Arg, c.161C>T - p.Ser54Leu). One of the individuals was mosaic for the latter variant, while in all other cases the variant had occurred de novo.

Protein kinase A (PKA) is a tetrameric holoenzyme formed by the association of 2 catalytic (C) subunits with a regulatory (R) subunit dimer. Activation of PKA is achieved through binding of 2 cAMP molecules to each R-subunit, and unleashing(/dissociation) of C-subunits to engage substrates. PRKACA/B genes encode the Cα- and Cβ-subunits while the 4 functionally non-redundant regulatory subunits are encoded by PRKAR1A/1B/2A/2B genes.

The authors provide evidence that the variants confer increased sensitivity of PKA holoenzymes to activation by cAMP (compared to wt).

By performing ectopic expression of wt or mt PRKACA/B (variants studied : PRKACA p.Gly137Arg / PRKACB p.Gly235Arg) in NIH 3T3 fibroblasts, the authors demonstrate that inhibition of hedgehog signaling likely underlyies the developmental defects observed in affected individuals.

As for PRKACA, the authors cite another study where a 31-month old female with EvC syndrome diagnosis was found to harbor the aforementioned variant (NM_001304349.1:c.637G>A:p.Gly213Arg corresponding to NM_002730.4:c.409G>A / p.Gly137Arg) as a de novo event. Without additional evidence at the time, the variant was considered to be a candidate for this subject's phenotype (Monies et al 2019 – PMID: 31130284).
Sources: Literature
Congenital Heart Defect v0.78 PRKACB Konstantinos Varvagiannis gene: PRKACB was added
gene: PRKACB was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: PRKACB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PRKACB were set to 33058759
Phenotypes for gene: PRKACB were set to Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability
Penetrance for gene: PRKACB were set to Complete
Mode of pathogenicity for gene: PRKACB 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: PRKACB was set to GREEN
Added comment: Palencia-Campos et al (2020 - PMID: 33058759) report on the phenotype of 3 individuals heterozygous for PRKACA and 4 individuals heterozygous for PRKACB pathogenic variants.

The most characteristic features in all individuals with PRKACA/PRKACB mutation, included postaxial polydactyly of hands (6/7 bilateral, 1/7 unilateral) and feet (4/7 bilateral, 1/7 unilateral), brachydactyly and congenital heart defects (CHD 5/7) namely a common atrium or AVSD. Two individuals with PRKACA variant who did not have CHD had offspring with the same variant and an AVSD.

Other variably occurring features included short stature, limbs, narrow chest, abnormal teeth, oral frenula, nail dysplasia. One individual with PRKACB variant presented tumors.

Intellectual disability was reported in 2/4 individuals with PRKACB variant (1/4: mild, 1/4: severe). The 3 individuals with PRKACA variant did not present ID.

As the phenotype was overall suggestive of Ellis-van Creveld syndrome (or the allelic Weyers acrofacial dysostosis), although these diagnoses were ruled out following analysis of EVC and EVC2 genes.

WES was carried out in all.

PRKACA : A single heterozygous missense variant was identified in 3 individuals from 3 families (NM_002730.4:c.409G>A / p.Gly137Arg) with 1 of the probands harboring the variant in mosaic state (28% of reads) and having 2 similarly affected offspring. The variant was de novo in one individual and inherited in a third one having a similarly affected fetus (narrow thorax, postaxial polyd, AVSD).

PRKACB : 4 different variants were identified (NM_002731.3: p.His88Arg/Asn, p.Gly235Arg, c.161C>T - p.Ser54Leu). One of the individuals was mosaic for the latter variant, while in all other cases the variant had occurred de novo.

Protein kinase A (PKA) is a tetrameric holoenzyme formed by the association of 2 catalytic (C) subunits with a regulatory (R) subunit dimer. Activation of PKA is achieved through binding of 2 cAMP molecules to each R-subunit, and unleashing(/dissociation) of C-subunits to engage substrates. PRKACA/B genes encode the Cα- and Cβ-subunits while the 4 functionally non-redundant regulatory subunits are encoded by PRKAR1A/1B/2A/2B genes.

The authors provide evidence that the variants confer increased sensitivity of PKA holoenzymes to activation by cAMP (compared to wt).

By performing ectopic expression of wt or mt PRKACA/B (variants studied : PRKACA p.Gly137Arg / PRKACB p.Gly235Arg) in NIH 3T3 fibroblasts, the authors demonstrate that inhibition of hedgehog signaling likely underlyies the developmental defects observed in affected individuals.

As for PRKACA, the authors cite another study where a 31-month old female with EvC syndrome diagnosis was found to harbor the aforementioned variant (NM_001304349.1:c.637G>A:p.Gly213Arg corresponding to NM_002730.4:c.409G>A / p.Gly137Arg) as a de novo event. Without additional evidence at the time, the variant was considered to be a candidate for this subject's phenotype (Monies et al 2019 – PMID: 31130284).
Sources: Literature
Polydactyly v0.180 PRKACB Konstantinos Varvagiannis gene: PRKACB was added
gene: PRKACB was added to Polydactyly. Sources: Literature
Mode of inheritance for gene: PRKACB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PRKACB were set to 33058759
Phenotypes for gene: PRKACB were set to Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability
Penetrance for gene: PRKACB were set to Complete
Mode of pathogenicity for gene: PRKACB 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: PRKACB was set to GREEN
Added comment: Palencia-Campos et al (2020 - PMID: 33058759) report on the phenotype of 3 individuals heterozygous for PRKACA and 4 individuals heterozygous for PRKACB pathogenic variants.

The most characteristic features in all individuals with PRKACA/PRKACB mutation, included postaxial polydactyly of hands (6/7 bilateral, 1/7 unilateral) and feet (4/7 bilateral, 1/7 unilateral), brachydactyly and congenital heart defects (CHD 5/7) namely a common atrium or AVSD. Two individuals with PRKACA variant who did not have CHD had offspring with the same variant and an AVSD.

Other variably occurring features included short stature, limbs, narrow chest, abnormal teeth, oral frenula, nail dysplasia. One individual with PRKACB variant presented tumors.

Intellectual disability was reported in 2/4 individuals with PRKACB variant (1/4: mild, 1/4: severe). The 3 individuals with PRKACA variant did not present ID.

As the phenotype was overall suggestive of Ellis-van Creveld syndrome (or the allelic Weyers acrofacial dysostosis), although these diagnoses were ruled out following analysis of EVC and EVC2 genes.

WES was carried out in all.

PRKACA : A single heterozygous missense variant was identified in 3 individuals from 3 families (NM_002730.4:c.409G>A / p.Gly137Arg) with 1 of the probands harboring the variant in mosaic state (28% of reads) and having 2 similarly affected offspring. The variant was de novo in one individual and inherited in a third one having a similarly affected fetus (narrow thorax, postaxial polyd, AVSD).

PRKACB : 4 different variants were identified (NM_002731.3: p.His88Arg/Asn, p.Gly235Arg, c.161C>T - p.Ser54Leu). One of the individuals was mosaic for the latter variant, while in all other cases the variant had occurred de novo.

Protein kinase A (PKA) is a tetrameric holoenzyme formed by the association of 2 catalytic (C) subunits with a regulatory (R) subunit dimer. Activation of PKA is achieved through binding of 2 cAMP molecules to each R-subunit, and unleashing(/dissociation) of C-subunits to engage substrates. PRKACA/B genes encode the Cα- and Cβ-subunits while the 4 functionally non-redundant regulatory subunits are encoded by PRKAR1A/1B/2A/2B genes.

The authors provide evidence that the variants confer increased sensitivity of PKA holoenzymes to activation by cAMP (compared to wt).

By performing ectopic expression of wt or mt PRKACA/B (variants studied : PRKACA p.Gly137Arg / PRKACB p.Gly235Arg) in NIH 3T3 fibroblasts, the authors demonstrate that inhibition of hedgehog signaling likely underlyies the developmental defects observed in affected individuals.

As for PRKACA, the authors cite another study where a 31-month old female with EvC syndrome diagnosis was found to harbor the aforementioned variant (NM_001304349.1:c.637G>A:p.Gly213Arg corresponding to NM_002730.4:c.409G>A / p.Gly137Arg) as a de novo event. Without additional evidence at the time, the variant was considered to be a candidate for this subject's phenotype (Monies et al 2019 – PMID: 31130284).
Sources: Literature
Polydactyly v0.180 PRKACA Konstantinos Varvagiannis gene: PRKACA was added
gene: PRKACA was added to Polydactyly. Sources: Literature
Mode of inheritance for gene: PRKACA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PRKACA were set to 33058759; 31130284
Phenotypes for gene: PRKACA were set to Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability
Penetrance for gene: PRKACA were set to Complete
Mode of pathogenicity for gene: PRKACA 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: PRKACA was set to GREEN
Added comment: Palencia-Campos et al (2020 - PMID: 33058759) report on the phenotype of 3 individuals heterozygous for PRKACA and 4 individuals heterozygous for PRKACB pathogenic variants.

The most characteristic features in all individuals with PRKACA/PRKACB mutation, included postaxial polydactyly of hands (6/7 bilateral, 1/7 unilateral) and feet (4/7 bilateral, 1/7 unilateral), brachydactyly and congenital heart defects (CHD 5/7) namely a common atrium or AVSD. Two individuals with PRKACA variant who did not have CHD had offspring with the same variant and an AVSD.

Other variably occurring features included short stature, limbs, narrow chest, abnormal teeth, oral frenula, nail dysplasia. One individual with PRKACB variant presented tumors.

Intellectual disability was reported in 2/4 individuals with PRKACB variant (1/4: mild, 1/4: severe). The 3 individuals with PRKACA variant did not present ID.

As the phenotype was overall suggestive of Ellis-van Creveld syndrome (or the allelic Weyers acrofacial dysostosis), although these diagnoses were ruled out following analysis of EVC and EVC2 genes.

WES was carried out in all.

PRKACA : A single heterozygous missense variant was identified in 3 individuals from 3 families (NM_002730.4:c.409G>A / p.Gly137Arg) with 1 of the probands harboring the variant in mosaic state (28% of reads) and having 2 similarly affected offspring. The variant was de novo in one individual and inherited in a third one having a similarly affected fetus (narrow thorax, postaxial polyd, AVSD).

PRKACB : 4 different variants were identified (NM_002731.3: p.His88Arg/Asn, p.Gly235Arg, c.161C>T - p.Ser54Leu). One of the individuals was mosaic for the latter variant, while in all other cases the variant had occurred de novo.

Protein kinase A (PKA) is a tetrameric holoenzyme formed by the association of 2 catalytic (C) subunits with a regulatory (R) subunit dimer. Activation of PKA is achieved through binding of 2 cAMP molecules to each R-subunit, and unleashing(/dissociation) of C-subunits to engage substrates. PRKACA/B genes encode the Cα- and Cβ-subunits while the 4 functionally non-redundant regulatory subunits are encoded by PRKAR1A/1B/2A/2B genes.

The authors provide evidence that the variants confer increased sensitivity of PKA holoenzymes to activation by cAMP (compared to wt).

By performing ectopic expression of wt or mt PRKACA/B (variants studied : PRKACA p.Gly137Arg / PRKACB p.Gly235Arg) in NIH 3T3 fibroblasts, the authors demonstrate that inhibition of hedgehog signaling likely underlyies the developmental defects observed in affected individuals.

As for PRKACA, the authors cite another study where a 31-month old female with EvC syndrome diagnosis was found to harbor the aforementioned variant (NM_001304349.1:c.637G>A:p.Gly213Arg corresponding to NM_002730.4:c.409G>A / p.Gly137Arg) as a de novo event. Without additional evidence at the time, the variant was considered to be a candidate for this subject's phenotype (Monies et al 2019 – PMID: 31130284).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3102 PRKACB Konstantinos Varvagiannis edited their review of gene: PRKACB: Changed mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability syndromic and non-syndromic v0.3102 PRKACB Konstantinos Varvagiannis gene: PRKACB was added
gene: PRKACB was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PRKACB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PRKACB were set to 33058759
Phenotypes for gene: PRKACB were set to Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability
Penetrance for gene: PRKACB were set to Complete
Review for gene: PRKACB was set to AMBER
Added comment: ID was a feature in 2/4 individuals with PRKACB pathogenic variant reported to date.
------
Palencia-Campos et al (2020 - PMID: 33058759) report on the phenotype of 3 individuals heterozygous for PRKACA and 4 individuals heterozygous for PRKACB pathogenic variants.

The most characteristic features in all individuals with PRKACA/PRKACB mutation, included postaxial polydactyly of hands (6/7 bilateral, 1/7 unilateral) and feet (4/7 bilateral, 1/7 unilateral), brachydactyly and congenital heart defects (CHD 5/7) namely a common atrium or AVSD. Two individuals with PRKACA variant who did not have CHD had offspring with the same variant and an AVSD.

Other variably occurring features included short stature, limbs, narrow chest, abnormal teeth, oral frenula, nail dysplasia. One individual with PRKACB variant presented tumors.

Intellectual disability was reported in 2/4 individuals with PRKACB variant (1/4: mild, 1/4: severe). The 3 individuals with PRKACA variant did not present ID.

As the phenotype was overall suggestive of Ellis-van Creveld syndrome (or the allelic Weyers acrofacial dysostosis), although these diagnoses were ruled out following analysis of EVC and EVC2 genes.

WES was carried out in all.

PRKACA : A single heterozygous missense variant was identified in 3 individuals from 3 families (NM_002730.4:c.409G>A / p.Gly137Arg) with 1 of the probands harboring the variant in mosaic state (28% of reads) and having 2 similarly affected offspring. The variant was de novo in one individual and inherited in a third one having a similarly affected fetus (narrow thorax, postaxial polyd, AVSD).

PRKACB : 4 different variants were identified (NM_002731.3: p.His88Arg/Asn, p.Gly235Arg, c.161C>T - p.Ser54Leu). One of the individuals was mosaic for the latter variant, while in all other cases the variant had occurred de novo.

Protein kinase A (PKA) is a tetrameric holoenzyme formed by the association of 2 catalytic (C) subunits with a regulatory (R) subunit dimer. Activation of PKA is achieved through binding of 2 cAMP molecules to each R-subunit, and unleashing(/dissociation) of C-subunits to engage substrates. PRKACA/B genes encode the Cα- and Cβ-subunits while the 4 functionally non-redundant regulatory subunits are encoded by PRKAR1A/1B/2A/2B genes.

The authors provide evidence that the variants confer increased sensitivity of PKA holoenzymes to activation by cAMP (compared to wt).

By performing ectopic expression of wt or mt PRKACA/B (variants studied : PRKACA p.Gly137Arg / PRKACB p.Gly235Arg) in NIH 3T3 fibroblasts, the authors demonstrate that inhibition of hedgehog signaling likely underlyies the developmental defects observed in affected individuals.

As for PRKACA, the authors cite another study where a 31-month old female with EvC syndrome diagnosis was found to harbor the aforementioned variant (NM_001304349.1:c.637G>A:p.Gly213Arg corresponding to NM_002730.4:c.409G>A / p.Gly137Arg) as a de novo event. Without additional evidence at the time, the variant was considered to be a candidate for this subject's phenotype (Monies et al 2019 – PMID: 31130284).
Sources: Literature
Regression v0.180 SHANK3 Konstantinos Varvagiannis gene: SHANK3 was added
gene: SHANK3 was added to Regression. Sources: Literature
Mode of inheritance for gene: SHANK3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SHANK3 were set to 32050889, 29719671
Phenotypes for gene: SHANK3 were set to # 606232. PHELAN-MCDERMID SYNDROME - PHMDS
Penetrance for gene: SHANK3 were set to Complete
Review for gene: SHANK3 was set to GREEN
Added comment: Regression has been reported in several individuals with Phelan-McDermid syndrome due to SHANK3 variants or deletions encompassing this gene.
Sources: Literature
Regression v0.180 SCO1 Zornitza Stark Marked gene: SCO1 as ready
Regression v0.180 SCO1 Zornitza Stark Gene: sco1 has been classified as Red List (Low Evidence).
Regression v0.180 SCO1 Zornitza Stark Phenotypes for gene: SCO1 were changed from to Mitochondrial complex IV deficiency, nuclear type 4, MIM# 619048
Regression v0.179 SCO1 Zornitza Stark Publications for gene: SCO1 were set to
Regression v0.178 SCO1 Zornitza Stark Mode of inheritance for gene: SCO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Regression v0.177 SCO1 Zornitza Stark Classified gene: SCO1 as Red List (low evidence)
Regression v0.177 SCO1 Zornitza Stark Gene: sco1 has been classified as Red List (Low Evidence).
Regression v0.176 SCO1 Zornitza Stark reviewed gene: SCO1: Rating: RED; Mode of pathogenicity: None; Publications: 11013136, 19295170, 31352446, 23878101; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 4, MIM# 619048; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5102 SCO1 Zornitza Stark Marked gene: SCO1 as ready
Mendeliome v0.5102 SCO1 Zornitza Stark Gene: sco1 has been classified as Green List (High Evidence).
Mendeliome v0.5102 SCO1 Zornitza Stark Phenotypes for gene: SCO1 were changed from to Mitochondrial complex IV deficiency, nuclear type 4, MIM# 619048
Mendeliome v0.5101 SCO1 Zornitza Stark Publications for gene: SCO1 were set to
Mendeliome v0.5100 SCO1 Zornitza Stark Mode of inheritance for gene: SCO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5099 SCO1 Zornitza Stark reviewed gene: SCO1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11013136, 19295170, 31352446, 23878101; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 4, MIM# 619048; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.523 SCO1 Zornitza Stark Marked gene: SCO1 as ready
Mitochondrial disease v0.523 SCO1 Zornitza Stark Gene: sco1 has been classified as Green List (High Evidence).
Mitochondrial disease v0.523 SCO1 Zornitza Stark Phenotypes for gene: SCO1 were changed from to Mitochondrial complex IV deficiency, nuclear type 4, MIM# 619048
Mitochondrial disease v0.522 SCO1 Zornitza Stark Publications for gene: SCO1 were set to
Mitochondrial disease v0.521 SCO1 Zornitza Stark Mode of inheritance for gene: SCO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.520 SCO1 Zornitza Stark reviewed gene: SCO1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11013136, 19295170, 31352446, 23878101; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 4, MIM# 619048; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3102 COX10 Zornitza Stark Marked gene: COX10 as ready
Intellectual disability syndromic and non-syndromic v0.3102 COX10 Zornitza Stark Gene: cox10 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3102 COX10 Zornitza Stark Phenotypes for gene: COX10 were changed from to Mitochondrial complex IV deficiency, nuclear type 3, MIM# 619046
Intellectual disability syndromic and non-syndromic v0.3101 COX10 Zornitza Stark Publications for gene: COX10 were set to
Intellectual disability syndromic and non-syndromic v0.3100 COX10 Zornitza Stark Mode of inheritance for gene: COX10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3099 COX10 Zornitza Stark reviewed gene: COX10: Rating: GREEN; Mode of pathogenicity: None; Publications: 10767350, 12928484, 15455402, 27290639; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 3, MIM# 619046; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Regression v0.176 COX10 Zornitza Stark Marked gene: COX10 as ready
Regression v0.176 COX10 Zornitza Stark Gene: cox10 has been classified as Green List (High Evidence).
Regression v0.176 COX10 Zornitza Stark Phenotypes for gene: COX10 were changed from to Mitochondrial complex IV deficiency, nuclear type 3, MIM# 619046
Regression v0.175 COX10 Zornitza Stark Publications for gene: COX10 were set to
Regression v0.174 COX10 Zornitza Stark Mode of inheritance for gene: COX10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Regression v0.173 COX10 Zornitza Stark reviewed gene: COX10: Rating: GREEN; Mode of pathogenicity: None; Publications: 10767350, 12928484, 15455402, 27290639; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 3, MIM# 619046; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5099 COX10 Zornitza Stark Marked gene: COX10 as ready
Mendeliome v0.5099 COX10 Zornitza Stark Gene: cox10 has been classified as Green List (High Evidence).
Mendeliome v0.5099 COX10 Zornitza Stark Phenotypes for gene: COX10 were changed from to Mitochondrial complex IV deficiency, nuclear type 3, MIM# 619046
Mendeliome v0.5098 COX10 Zornitza Stark Publications for gene: COX10 were set to
Mendeliome v0.5097 COX10 Zornitza Stark Mode of inheritance for gene: COX10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5096 COX10 Zornitza Stark reviewed gene: COX10: Rating: GREEN; Mode of pathogenicity: None; Publications: 10767350, 12928484, 15455402, 27290639; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 3, MIM# 619046; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.520 COX10 Zornitza Stark Marked gene: COX10 as ready
Mitochondrial disease v0.520 COX10 Zornitza Stark Gene: cox10 has been classified as Green List (High Evidence).
Mitochondrial disease v0.520 COX10 Zornitza Stark Phenotypes for gene: COX10 were changed from to Mitochondrial complex IV deficiency, nuclear type 3, MIM# 619046
Mitochondrial disease v0.519 COX10 Zornitza Stark Publications for gene: COX10 were set to
Mitochondrial disease v0.518 COX10 Zornitza Stark Mode of inheritance for gene: COX10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.517 COX10 Zornitza Stark reviewed gene: COX10: Rating: GREEN; Mode of pathogenicity: None; Publications: 10767350, 12928484, 15455402, 27290639; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 3, MIM# 619046; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Myasthenia v0.43 RAPSN Zornitza Stark Marked gene: RAPSN as ready
Congenital Myasthenia v0.43 RAPSN Zornitza Stark Gene: rapsn has been classified as Green List (High Evidence).
Congenital Myasthenia v0.43 RAPSN Zornitza Stark Publications for gene: RAPSN were set to
Congenital Myasthenia v0.42 RAPSN Zornitza Stark Tag SV/CNV tag was added to gene: RAPSN.
Tag founder tag was added to gene: RAPSN.
Congenital Myasthenia v0.42 RAPSN Zornitza Stark reviewed gene: RAPSN: Rating: GREEN; Mode of pathogenicity: None; Publications: 11791205, 14504330, 20930056, 25194721; Phenotypes: Myasthenic syndrome, congenital, 11, associated with acetylcholine receptor deficiency, MIM#616326; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Myasthenia v0.42 LRP4 Zornitza Stark Marked gene: LRP4 as ready
Congenital Myasthenia v0.42 LRP4 Zornitza Stark Gene: lrp4 has been classified as Green List (High Evidence).
Congenital Myasthenia v0.42 LRP4 Zornitza Stark Publications for gene: LRP4 were set to
Congenital Myasthenia v0.41 LRP4 Zornitza Stark reviewed gene: LRP4: Rating: GREEN; Mode of pathogenicity: None; Publications: 24234652, 26052878, 24200689; Phenotypes: Myasthenic syndrome, congenital, 17, MIM# 616304; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Myasthenia v0.41 LAMA5 Zornitza Stark Marked gene: LAMA5 as ready
Congenital Myasthenia v0.41 LAMA5 Zornitza Stark Gene: lama5 has been classified as Red List (Low Evidence).
Congenital Myasthenia v0.41 LAMA5 Zornitza Stark Phenotypes for gene: LAMA5 were changed from muscle weakness, myopia, and facial tics to Presynaptic congenital myasthenic syndrome
Congenital Myasthenia v0.40 LAMA5 Zornitza Stark Publications for gene: LAMA5 were set to 28544784
Congenital Myasthenia v0.39 LAMA5 Zornitza Stark reviewed gene: LAMA5: Rating: RED; Mode of pathogenicity: None; Publications: 28544784, 29377152; Phenotypes: Presynaptic congenital myasthenic syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Myasthenia v0.39 DPAGT1 Zornitza Stark Marked gene: DPAGT1 as ready
Congenital Myasthenia v0.39 DPAGT1 Zornitza Stark Gene: dpagt1 has been classified as Green List (High Evidence).
Congenital Myasthenia v0.39 DPAGT1 Zornitza Stark Publications for gene: DPAGT1 were set to
Congenital Myasthenia v0.38 DPAGT1 Zornitza Stark reviewed gene: DPAGT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22742743, 29356258, 28712839, 28662078; Phenotypes: Myasthenic syndrome, congenital, 13, with tubular aggregates, MIM# 614750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.173 GFPT1 Zornitza Stark changed review comment from: 15 unrelated families reported with bi-allelic variants and a congenital myasthenic syndrome. Two families with leukoencephalopathy as well as CMS.

The GFPT1 gene encodes an isoform of glutamine:fructose-6-phosphate amidotransferase (GFAT), which catalyzes the transfer of an amino group from glutamine onto fructose-6-phosphate, yielding glucosamine 6-phosphate and glutamate. It is the first and rate-limiting enzyme of the hexosamine biosynthetic pathway. Hexosamine is the obligatory source of essential amino sugars for the synthesis of glycoproteins, glycolipids, and proteoglycans. Muscle samples from several patients showed decreased protein glycosylation.; to: 15 unrelated families reported with bi-allelic variants and a congenital myasthenic syndrome. Two families with leukoencephalopathy as well as CMS.

The GFPT1 gene encodes an isoform of glutamine:fructose-6-phosphate amidotransferase (GFAT), which catalyzes the transfer of an amino group from glutamine onto fructose-6-phosphate, yielding glucosamine 6-phosphate and glutamate. It is the first and rate-limiting enzyme of the hexosamine biosynthetic pathway. Hexosamine is the obligatory source of essential amino sugars for the synthesis of glycoproteins, glycolipids, and proteoglycans. Muscle samples from several patients showed decreased protein glycosylation, suggesting this is a disorder of glycosylation. However, there is also some data put forward in PMID 30635494 that this may be a mitochondrial condition.
Congenital Disorders of Glycosylation v0.173 GFPT1 Zornitza Stark Marked gene: GFPT1 as ready
Congenital Disorders of Glycosylation v0.173 GFPT1 Zornitza Stark Gene: gfpt1 has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v0.173 GFPT1 Zornitza Stark Phenotypes for gene: GFPT1 were changed from to Myasthenia, congenital, 12, with tubular aggregates, 610542; Limb-girdle congenital myasthenic syndrome; Leukoencephalopathy
Congenital Disorders of Glycosylation v0.172 GFPT1 Zornitza Stark Publications for gene: GFPT1 were set to
Congenital Disorders of Glycosylation v0.171 GFPT1 Zornitza Stark Mode of inheritance for gene: GFPT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.170 GFPT1 Zornitza Stark reviewed gene: GFPT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21310273, 30635494; Phenotypes: Myasthenia, congenital, 12, with tubular aggregates, 610542, Limb-girdle congenital myasthenic syndrome, Leukoencephalopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5096 GFPT1 Zornitza Stark Marked gene: GFPT1 as ready
Mendeliome v0.5096 GFPT1 Zornitza Stark Gene: gfpt1 has been classified as Green List (High Evidence).
Mendeliome v0.5096 GFPT1 Zornitza Stark Phenotypes for gene: GFPT1 were changed from to Myasthenia, congenital, 12, with tubular aggregates, 610542; Limb-girdle congenital myasthenic syndrome; Leukoencephalopathy
Mendeliome v0.5095 GFPT1 Zornitza Stark Publications for gene: GFPT1 were set to
Mendeliome v0.5094 GFPT1 Zornitza Stark Mode of inheritance for gene: GFPT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5093 GFPT1 Zornitza Stark reviewed gene: GFPT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21310273, 30635494; Phenotypes: Myasthenia, congenital, 12, with tubular aggregates, 610542, Limb-girdle congenital myasthenic syndrome, Leukoencephalopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Myasthenia v0.38 GFPT1 Zornitza Stark Marked gene: GFPT1 as ready
Congenital Myasthenia v0.38 GFPT1 Zornitza Stark Gene: gfpt1 has been classified as Green List (High Evidence).
Congenital Myasthenia v0.38 GFPT1 Zornitza Stark Publications for gene: GFPT1 were set to
Congenital Myasthenia v0.37 GFPT1 Zornitza Stark reviewed gene: GFPT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21310273, 30635494]; Phenotypes: Myasthenia, congenital, 12, with tubular aggregates, MIM# 610542; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Myasthenia v0.37 GMPPB Zornitza Stark Marked gene: GMPPB as ready
Congenital Myasthenia v0.37 GMPPB Zornitza Stark Gene: gmppb has been classified as Green List (High Evidence).
Congenital Myasthenia v0.37 GMPPB Zornitza Stark Phenotypes for gene: GMPPB were changed from Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 with features of congenital myasthenic syndrome to Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 with features of congenital myasthenic syndrome
Congenital Myasthenia v0.36 GMPPB Zornitza Stark reviewed gene: GMPPB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital myasthenic syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hair disorders v0.39 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Mendeliome v0.5093 BMP7 Zornitza Stark Marked gene: BMP7 as ready
Mendeliome v0.5093 BMP7 Zornitza Stark Gene: bmp7 has been classified as Red List (Low Evidence).
Mendeliome v0.5093 BMP7 Zornitza Stark gene: BMP7 was added
gene: BMP7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BMP7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BMP7 were set to 32266521; 24429398
Phenotypes for gene: BMP7 were set to Non-syndromic metopic craniosynostosis
Mode of pathogenicity for gene: BMP7 was set to Other
Review for gene: BMP7 was set to RED
Added comment: Non-syndromic metopic craniosynostosis: PMID 32266521 reports rs6127972 as a susceptibility SNP for non-syndromic metopic craniosynostosis

CAKUT: PMID 24429398 1 family with mouse model in large cohort of CAKUT.
Sources: Literature
Craniosynostosis v1.11 BMP7 Zornitza Stark Marked gene: BMP7 as ready
Craniosynostosis v1.11 BMP7 Zornitza Stark Gene: bmp7 has been classified as Red List (Low Evidence).
Craniosynostosis v1.11 BMP7 Zornitza Stark gene: BMP7 was added
gene: BMP7 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: BMP7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BMP7 were set to 32266521
Phenotypes for gene: BMP7 were set to Non-syndromic metopic craniosynostosis
Mode of pathogenicity for gene: BMP7 was set to Other
Review for gene: BMP7 was set to RED
Added comment: rs6127972 identified as a susceptibility SNP for non-syndromic metopic craniosynostosis.
Sources: Literature
Congenital Myasthenia v0.36 MUSK Zornitza Stark Marked gene: MUSK as ready
Congenital Myasthenia v0.36 MUSK Zornitza Stark Gene: musk has been classified as Green List (High Evidence).
Congenital Myasthenia v0.36 MUSK Zornitza Stark Publications for gene: MUSK were set to
Congenital Myasthenia v0.35 MUSK Zornitza Stark reviewed gene: MUSK: Rating: GREEN; Mode of pathogenicity: None; Publications: 15496425, 19949040, 20371544, 32253145; Phenotypes: Myasthenic syndrome, congenital, 9, associated with acetylcholine receptor deficiency, MIM# 616325; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hydrocephalus_Ventriculomegaly v0.69 MTOR Zornitza Stark Marked gene: MTOR as ready
Hydrocephalus_Ventriculomegaly v0.69 MTOR Zornitza Stark Gene: mtor has been classified as Amber List (Moderate Evidence).
Hydrocephalus_Ventriculomegaly v0.69 MTOR Zornitza Stark Classified gene: MTOR as Amber List (moderate evidence)
Hydrocephalus_Ventriculomegaly v0.69 MTOR Zornitza Stark Gene: mtor has been classified as Amber List (Moderate Evidence).
Hydrocephalus_Ventriculomegaly v0.68 MTOR Zornitza Stark gene: MTOR was added
gene: MTOR was added to Hydrocephalus_Ventriculomegaly. Sources: Literature
Mode of inheritance for gene: MTOR was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MTOR were set to 33077954
Phenotypes for gene: MTOR were set to Congenital hydrocephalus; macrocephaly
Mode of pathogenicity for gene: MTOR was set to Other
Review for gene: MTOR was set to AMBER
Added comment: Two de novo missense variants reported in this cohort, along with other variants involved in the MTOR pathway. GOF postulated.
Sources: Literature
Hydrocephalus_Ventriculomegaly v0.67 SMARCC1 Zornitza Stark Publications for gene: SMARCC1 were set to 33077954
Mendeliome v0.5092 SMARCC1 Zornitza Stark Publications for gene: SMARCC1 were set to 33077954
Mendeliome v0.5091 SMARCC1 Zornitza Stark changed review comment from: Three de novo variants, two LOF, one missense, reported in this hydrocephalus cohort.
Sources: Literature; to: Three de novo variants, two LOF, one missense, reported in this hydrocephalus cohort. Supportive mouse model.
Sources: Literature
Mendeliome v0.5091 SMARCC1 Zornitza Stark edited their review of gene: SMARCC1: Changed publications: 33077954, 24170322
Hydrocephalus_Ventriculomegaly v0.66 SMARCC1 Zornitza Stark changed review comment from: Three de novo variants, two LOF, one missense, reported in this hydrocephalus cohort.
Sources: Literature; to: Three de novo variants, two LOF, one missense, reported in this hydrocephalus cohort. Supportive mouse model.
Sources: Literature
Hydrocephalus_Ventriculomegaly v0.66 SMARCC1 Zornitza Stark edited their review of gene: SMARCC1: Changed publications: 33077954, 24170322
Hydrocephalus_Ventriculomegaly v0.66 FOXJ1 Zornitza Stark Marked gene: FOXJ1 as ready
Hydrocephalus_Ventriculomegaly v0.66 FOXJ1 Zornitza Stark Gene: foxj1 has been classified as Green List (High Evidence).
Hydrocephalus_Ventriculomegaly v0.66 FOXJ1 Zornitza Stark Classified gene: FOXJ1 as Green List (high evidence)
Hydrocephalus_Ventriculomegaly v0.66 FOXJ1 Zornitza Stark Gene: foxj1 has been classified as Green List (High Evidence).
Hydrocephalus_Ventriculomegaly v0.65 FOXJ1 Zornitza Stark changed review comment from: Two de novo LOF reported as part of this large hydrocephalus cohort.
Sources: Literature; to: 8 unrelated individuals reported with de novo variants in this gene, primary ciliary dyskinesia and significant obstructive hydrocephalus.
Sources: Literature
Hydrocephalus_Ventriculomegaly v0.65 FOXJ1 Zornitza Stark edited their review of gene: FOXJ1: Changed rating: GREEN; Changed publications: 33077954, 31630787
Hydrocephalus_Ventriculomegaly v0.65 FOXJ1 Zornitza Stark gene: FOXJ1 was added
gene: FOXJ1 was added to Hydrocephalus_Ventriculomegaly. Sources: Literature
Mode of inheritance for gene: FOXJ1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FOXJ1 were set to 33077954
Phenotypes for gene: FOXJ1 were set to Congenital hydrocephalus
Review for gene: FOXJ1 was set to AMBER
Added comment: Two de novo LOF reported as part of this large hydrocephalus cohort.
Sources: Literature
Mendeliome v0.5091 SMARCC1 Zornitza Stark Marked gene: SMARCC1 as ready
Mendeliome v0.5091 SMARCC1 Zornitza Stark Gene: smarcc1 has been classified as Green List (High Evidence).
Mendeliome v0.5091 SMARCC1 Zornitza Stark Classified gene: SMARCC1 as Green List (high evidence)
Mendeliome v0.5091 SMARCC1 Zornitza Stark Gene: smarcc1 has been classified as Green List (High Evidence).
Mendeliome v0.5090 SMARCC1 Zornitza Stark gene: SMARCC1 was added
gene: SMARCC1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SMARCC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMARCC1 were set to 33077954
Phenotypes for gene: SMARCC1 were set to Congenital hydrocephalus
Review for gene: SMARCC1 was set to GREEN
Added comment: Three de novo variants, two LOF, one missense, reported in this hydrocephalus cohort.
Sources: Literature
Hydrocephalus_Ventriculomegaly v0.64 SMARCC1 Zornitza Stark Marked gene: SMARCC1 as ready
Hydrocephalus_Ventriculomegaly v0.64 SMARCC1 Zornitza Stark Gene: smarcc1 has been classified as Green List (High Evidence).
Hydrocephalus_Ventriculomegaly v0.64 SMARCC1 Zornitza Stark Classified gene: SMARCC1 as Green List (high evidence)
Hydrocephalus_Ventriculomegaly v0.64 SMARCC1 Zornitza Stark Gene: smarcc1 has been classified as Green List (High Evidence).
Hydrocephalus_Ventriculomegaly v0.63 SMARCC1 Zornitza Stark gene: SMARCC1 was added
gene: SMARCC1 was added to Hydrocephalus_Ventriculomegaly. Sources: Literature
Mode of inheritance for gene: SMARCC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMARCC1 were set to 33077954
Phenotypes for gene: SMARCC1 were set to Congenital hydrocephalus
Review for gene: SMARCC1 was set to GREEN
Added comment: Three de novo variants, two LOF, one missense, reported in this hydrocephalus cohort.
Sources: Literature
Congenital Myasthenia v0.35 SCN4A Zornitza Stark Marked gene: SCN4A as ready
Congenital Myasthenia v0.35 SCN4A Zornitza Stark Gene: scn4a has been classified as Green List (High Evidence).
Congenital Myasthenia v0.35 SCN4A Zornitza Stark Publications for gene: SCN4A were set to
Congenital Myasthenia v0.34 SCN4A Zornitza Stark reviewed gene: SCN4A: Rating: GREEN; Mode of pathogenicity: None; Publications: 12766226, 25707578, 32849172; Phenotypes: Myasthenic syndrome, congenital, 16, MIM# 614198; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5089 SLC18A3 Zornitza Stark Marked gene: SLC18A3 as ready
Mendeliome v0.5089 SLC18A3 Zornitza Stark Gene: slc18a3 has been classified as Green List (High Evidence).
Mendeliome v0.5089 SLC18A3 Zornitza Stark Phenotypes for gene: SLC18A3 were changed from to Myasthenic syndrome, congenital, 21, presynaptic, MIM#617239
Mendeliome v0.5088 SLC18A3 Zornitza Stark Publications for gene: SLC18A3 were set to
Mendeliome v0.5087 SLC18A3 Zornitza Stark Mode of inheritance for gene: SLC18A3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5086 SLC18A3 Zornitza Stark reviewed gene: SLC18A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 27590285, 20123977, 28188302, 31059209; Phenotypes: Myasthenic syndrome, congenital, 21, presynaptic, MIM#617239; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Myasthenia v0.34 SLC18A3 Zornitza Stark Marked gene: SLC18A3 as ready
Congenital Myasthenia v0.34 SLC18A3 Zornitza Stark Gene: slc18a3 has been classified as Green List (High Evidence).
Congenital Myasthenia v0.34 SLC18A3 Zornitza Stark Publications for gene: SLC18A3 were set to
Congenital Myasthenia v0.33 SLC18A3 Zornitza Stark reviewed gene: SLC18A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 27590285, 20123977, 28188302, 31059209; Phenotypes: Myasthenic syndrome, congenital, 21, presynaptic, MIM#617239; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Myasthenia v0.33 SLC5A7 Zornitza Stark Marked gene: SLC5A7 as ready
Congenital Myasthenia v0.33 SLC5A7 Zornitza Stark Gene: slc5a7 has been classified as Green List (High Evidence).
Congenital Myasthenia v0.33 SLC5A7 Zornitza Stark Publications for gene: SLC5A7 were set to
Congenital Myasthenia v0.32 SLC5A7 Zornitza Stark reviewed gene: SLC5A7: Rating: GREEN; Mode of pathogenicity: None; Publications: 27569547, 29189923, 30172469; Phenotypes: Myasthenic syndrome, congenital, 20, presynaptic, MIM# 617143; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Myasthenia v0.32 SYT2 Zornitza Stark Publications for gene: SYT2 were set to 25192047; 32776697; 32250532
Congenital Myasthenia v0.31 SYT2 Zornitza Stark changed review comment from: Mono-allelic disease, PMID 25192047: dominant missense variants in SYT2 reported as a rare cause of distal motor neuropathy and myasthenic syndrome, manifesting with stable or slowly progressive distal weakness of variable severity along with presynaptic NMJ impairment in two families. These variants are thought to have a dominant-negative effect on synaptic vesicle exocytosis, although the precise pathomechanism remains to be elucidated.

Bi-allelic disease: 32250532 and 32776697, 8 individuals from 6 families, with biallelic loss of function variants in SYT2, clinically manifesting with severe congenital onset hypotonia and weakness, with variable degrees of respiratory involvement. Electrodiagnostic findings consistent with a presynaptic congenital myasthenic syndrome (CMS) in some. Treatment with an acetylcholinesterase inhibitor pursued in 4 indviduals showed clinical improvement with increased strength and function.; to: Mono-allelic disease, PMID 25192047 and 30533528: dominant missense variants in SYT2 reported as a rare cause of distal motor neuropathy and myasthenic syndrome, manifesting with stable or slowly progressive distal weakness of variable severity along with presynaptic NMJ impairment in two families. These variants are thought to have a dominant-negative effect on synaptic vesicle exocytosis, although the precise pathomechanism remains to be elucidated.

Bi-allelic disease: 32250532 and 32776697, 8 individuals from 6 families, with biallelic loss of function variants in SYT2, clinically manifesting with severe congenital onset hypotonia and weakness, with variable degrees of respiratory involvement. Electrodiagnostic findings consistent with a presynaptic congenital myasthenic syndrome (CMS) in some. Treatment with an acetylcholinesterase inhibitor pursued in 4 indviduals showed clinical improvement with increased strength and function.
Congenital Myasthenia v0.31 SYT2 Zornitza Stark edited their review of gene: SYT2: Changed publications: 25192047, 32776697, 32250532, 30533528
Mendeliome v0.5086 SYT2 Zornitza Stark Publications for gene: SYT2 were set to 25192047; 32776697; 32250532
Mendeliome v0.5085 SYT2 Zornitza Stark changed review comment from: Mono-allelic disease, PMID 25192047: dominant missense variants in SYT2 reported as a rare cause of distal motor neuropathy and myasthenic syndrome, manifesting with stable or slowly progressive distal weakness of variable severity along with presynaptic NMJ impairment in two families. These variants are thought to have a dominant-negative effect on synaptic vesicle exocytosis, although the precise pathomechanism remains to be elucidated.

Bi-allelic disease: 32250532 and 32776697, 8 individuals from 6 families, with biallelic loss of function variants in SYT2, clinically manifesting with severe congenital onset hypotonia and weakness, with variable degrees of respiratory involvement. Electrodiagnostic findings consistent with a presynaptic congenital myasthenic syndrome (CMS) in some. Treatment with an acetylcholinesterase inhibitor pursued in 4 indviduals showed clinical improvement with increased strength and function.; to: Mono-allelic disease, PMID 25192047 and 30533528: dominant missense variants in SYT2 reported as a rare cause of distal motor neuropathy and myasthenic syndrome, manifesting with stable or slowly progressive distal weakness of variable severity along with presynaptic NMJ impairment in three families. These variants are thought to have a dominant-negative effect on synaptic vesicle exocytosis, although the precise pathomechanism remains to be elucidated.

Bi-allelic disease: 32250532 and 32776697, 8 individuals from 6 families, with biallelic loss of function variants in SYT2, clinically manifesting with severe congenital onset hypotonia and weakness, with variable degrees of respiratory involvement. Electrodiagnostic findings consistent with a presynaptic congenital myasthenic syndrome (CMS) in some. Treatment with an acetylcholinesterase inhibitor pursued in 4 indviduals showed clinical improvement with increased strength and function.
Mendeliome v0.5085 SYT2 Zornitza Stark edited their review of gene: SYT2: Changed publications: 25192047, 32776697, 32250532, 30533528
Mendeliome v0.5085 SYT2 Zornitza Stark Marked gene: SYT2 as ready
Mendeliome v0.5085 SYT2 Zornitza Stark Gene: syt2 has been classified as Green List (High Evidence).
Mendeliome v0.5085 SYT2 Zornitza Stark Phenotypes for gene: SYT2 were changed from to Myasthenic syndrome, congenital, 7, presynaptic, MIM# 616040
Mendeliome v0.5084 SYT2 Zornitza Stark Publications for gene: SYT2 were set to
Mendeliome v0.5083 SYT2 Zornitza Stark Mode of inheritance for gene: SYT2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5082 SYT2 Zornitza Stark reviewed gene: SYT2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25192047, 32776697, 32250532; Phenotypes: Myasthenic syndrome, congenital, 7, presynaptic, MIM# 616040; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital Myasthenia v0.31 SYT2 Zornitza Stark Marked gene: SYT2 as ready
Congenital Myasthenia v0.31 SYT2 Zornitza Stark Gene: syt2 has been classified as Green List (High Evidence).
Congenital Myasthenia v0.31 SYT2 Zornitza Stark Publications for gene: SYT2 were set to
Congenital Myasthenia v0.30 SYT2 Zornitza Stark Mode of inheritance for gene: SYT2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital Myasthenia v0.29 SYT2 Zornitza Stark reviewed gene: SYT2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25192047, 32776697, 32250532; Phenotypes: Myasthenic syndrome, congenital, 7, presynaptic, MIM# 616040; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital Myasthenia v0.29 DOK7 Zornitza Stark Marked gene: DOK7 as ready
Congenital Myasthenia v0.29 DOK7 Zornitza Stark Gene: dok7 has been classified as Green List (High Evidence).
Congenital Myasthenia v0.29 DOK7 Zornitza Stark Publications for gene: DOK7 were set to
Congenital Myasthenia v0.28 DOK7 Zornitza Stark reviewed gene: DOK7: Rating: GREEN; Mode of pathogenicity: None; Publications: 16917026, 18626973, 20147321, 16794080, 31453852, 29395672, 32360404; Phenotypes: Myasthenic syndrome, congenital, 10, MIM# 254300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Myasthenia v0.28 CHRNB1 Zornitza Stark Marked gene: CHRNB1 as ready
Congenital Myasthenia v0.28 CHRNB1 Zornitza Stark Gene: chrnb1 has been classified as Green List (High Evidence).
Congenital Myasthenia v0.28 CHRNB1 Zornitza Stark Publications for gene: CHRNB1 were set to
Congenital Myasthenia v0.27 CHRNB1 Zornitza Stark reviewed gene: CHRNB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 8872460, 8651643, 27375219, 32504635, 10562302,; Phenotypes: Myasthenic syndrome, congenital, 2A, slow-channel, MIM# 616313, Myasthenic syndrome, congenital, 2C, associated with acetylcholine receptor deficiency, MIM# 616314; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital Myasthenia v0.27 CHRNA1 Zornitza Stark Marked gene: CHRNA1 as ready
Congenital Myasthenia v0.27 CHRNA1 Zornitza Stark Gene: chrna1 has been classified as Green List (High Evidence).
Congenital Myasthenia v0.27 CHRNA1 Zornitza Stark Publications for gene: CHRNA1 were set to
Congenital Myasthenia v0.26 CHRNA1 Zornitza Stark reviewed gene: CHRNA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26910802, 10195214, 12588888, 15079006, 18806275, 7619526, 8872460, 9158151; Phenotypes: Myasthenic syndrome, congenital, 1A, slow-channel, MIM# 601462, Myasthenic syndrome, congenital, 1B, fast-channel , MIM#608930; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5082 CHAT Zornitza Stark Marked gene: CHAT as ready
Mendeliome v0.5082 CHAT Zornitza Stark Gene: chat has been classified as Green List (High Evidence).
Mendeliome v0.5082 CHAT Zornitza Stark Phenotypes for gene: CHAT were changed from to Congenital myasthenics syndrome associated with episodic apnea; Myasthenic syndrome, congenital, 6, presynaptic, 254210
Mendeliome v0.5081 CHAT Zornitza Stark Publications for gene: CHAT were set to
Mendeliome v0.5080 CHAT Zornitza Stark Mode of inheritance for gene: CHAT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5079 CHAT Zornitza Stark reviewed gene: CHAT: Rating: GREEN; Mode of pathogenicity: None; Publications: 11172068, 12756141, 31192527, 29518833, 29189923; Phenotypes: Congenital myasthenics syndrome associated with episodic apnea, Myasthenic syndrome, congenital, 6, presynaptic, 254210; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Myasthenia v0.26 CHAT Zornitza Stark Marked gene: CHAT as ready
Congenital Myasthenia v0.26 CHAT Zornitza Stark Gene: chat has been classified as Green List (High Evidence).
Congenital Myasthenia v0.26 CHAT Zornitza Stark Publications for gene: CHAT were set to
Congenital Myasthenia v0.25 CHAT Zornitza Stark reviewed gene: CHAT: Rating: GREEN; Mode of pathogenicity: None; Publications: 11172068, 12756141, 31192527, 29518833, 29189923; Phenotypes: Myasthenic syndrome, congenital, 6, presynaptic, MIM# 254210; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5079 ALG2 Zornitza Stark Tag founder tag was added to gene: ALG2.
Mendeliome v0.5079 ALG2 Zornitza Stark Marked gene: ALG2 as ready
Mendeliome v0.5079 ALG2 Zornitza Stark Gene: alg2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5079 ALG2 Zornitza Stark Phenotypes for gene: ALG2 were changed from to Myasthenic syndrome, congenital, 14, with tubular aggregates, MIM# 616228; Congenital disorder of glycosylation, type Ii, MIM# 607906
Mendeliome v0.5078 ALG2 Zornitza Stark Publications for gene: ALG2 were set to
Mendeliome v0.5077 ALG2 Zornitza Stark Mode of inheritance for gene: ALG2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5076 ALG2 Zornitza Stark Classified gene: ALG2 as Amber List (moderate evidence)
Mendeliome v0.5076 ALG2 Zornitza Stark Gene: alg2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5075 ALG2 Zornitza Stark reviewed gene: ALG2: Rating: AMBER; Mode of pathogenicity: None; Publications: 23404334, 24461433, 12684507; Phenotypes: Myasthenic syndrome, congenital, 14, with tubular aggregates, MIM# 616228, Congenital disorder of glycosylation, type Ii, MIM# 607906; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Myasthenia v0.25 ALG2 Zornitza Stark Tag founder tag was added to gene: ALG2.
Mendeliome v0.5075 AGRN Zornitza Stark Marked gene: AGRN as ready
Mendeliome v0.5075 AGRN Zornitza Stark Gene: agrn has been classified as Green List (High Evidence).
Congenital Myasthenia v0.25 ALG2 Zornitza Stark Marked gene: ALG2 as ready
Congenital Myasthenia v0.25 ALG2 Zornitza Stark Gene: alg2 has been classified as Amber List (Moderate Evidence).
Congenital Myasthenia v0.25 ALG2 Zornitza Stark Phenotypes for gene: ALG2 were changed from Congenital disorder of glycosylation CDG type Ii, 607906; Myasthenic syndrome, congenital, 14, with tubular aggregates, 616228 to Myasthenic syndrome, congenital, 14, with tubular aggregates, 616228
Congenital Myasthenia v0.24 ALG2 Zornitza Stark Publications for gene: ALG2 were set to
Congenital Myasthenia v0.23 ALG2 Zornitza Stark Classified gene: ALG2 as Amber List (moderate evidence)
Congenital Myasthenia v0.23 ALG2 Zornitza Stark Gene: alg2 has been classified as Amber List (Moderate Evidence).
Congenital Myasthenia v0.22 ALG2 Zornitza Stark reviewed gene: ALG2: Rating: AMBER; Mode of pathogenicity: None; Publications: 23404334, 24461433; Phenotypes: Myasthenic syndrome, congenital, 14, with tubular aggregates, MIM# 616228; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5075 AGRN Zornitza Stark Phenotypes for gene: AGRN were changed from to Myasthenic syndrome, congenital, 8, with pre- and postsynaptic defects, MIM# 615120
Mendeliome v0.5074 AGRN Zornitza Stark Publications for gene: AGRN were set to
Mendeliome v0.5073 AGRN Zornitza Stark Mode of inheritance for gene: AGRN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5072 AGRN Zornitza Stark reviewed gene: AGRN: Rating: GREEN; Mode of pathogenicity: None; Publications: 19631309, 22205389, 32221959; Phenotypes: Myasthenic syndrome, congenital, 8, with pre- and postsynaptic defects, MIM# 615120; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Myasthenia v0.22 AGRN Zornitza Stark Marked gene: AGRN as ready
Congenital Myasthenia v0.22 AGRN Zornitza Stark Gene: agrn has been classified as Green List (High Evidence).
Congenital Myasthenia v0.22 AGRN Zornitza Stark Publications for gene: AGRN were set to
Congenital Myasthenia v0.21 AGRN Zornitza Stark reviewed gene: AGRN: Rating: GREEN; Mode of pathogenicity: None; Publications: 19631309, 22205389, 32221959; Phenotypes: Myasthenic syndrome, congenital, 8, with pre- and postsynaptic defects, MIM# 615120; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Chromosome Breakage Disorders v0.32 ADAR Zornitza Stark Marked gene: ADAR as ready
Chromosome Breakage Disorders v0.32 ADAR Zornitza Stark Gene: adar has been classified as Red List (Low Evidence).
Chromosome Breakage Disorders v0.32 ADAR Zornitza Stark Phenotypes for gene: ADAR were changed from to Dyschromatosis symmetrica hereditaria, MIM# 127400
Chromosome Breakage Disorders v0.31 ADAR Zornitza Stark Mode of inheritance for gene: ADAR was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Chromosome Breakage Disorders v0.30 ADAR Zornitza Stark Classified gene: ADAR as Red List (low evidence)
Chromosome Breakage Disorders v0.30 ADAR Zornitza Stark Gene: adar has been classified as Red List (Low Evidence).
Chromosome Breakage Disorders v0.29 ADAR Zornitza Stark reviewed gene: ADAR: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Dyschromatosis symmetrica hereditaria, MIM# 127400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Chromosome Breakage Disorders v0.29 BRCA1 Zornitza Stark Marked gene: BRCA1 as ready
Chromosome Breakage Disorders v0.29 BRCA1 Zornitza Stark Gene: brca1 has been classified as Green List (High Evidence).
Chromosome Breakage Disorders v0.29 BRCA1 Zornitza Stark Classified gene: BRCA1 as Green List (high evidence)
Chromosome Breakage Disorders v0.29 BRCA1 Zornitza Stark Gene: brca1 has been classified as Green List (High Evidence).
Craniosynostosis v1.10 ZNF462 Zornitza Stark Phenotypes for gene: ZNF462 were changed from WEISS-KRUSZKA SYNDROME to Weiss-Kruszka syndrome, MIM#618619
Craniosynostosis v1.9 ZIC1 Zornitza Stark edited their review of gene: ZIC1: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v1.9 WDR35 Zornitza Stark Phenotypes for gene: WDR35 were changed from CRANIOECTODERMAL DYSPLASIA to Cranioectodermal dysplasia 2, MIM# 613610
Craniosynostosis v1.8 WDR35 Zornitza Stark reviewed gene: WDR35: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cranioectodermal dysplasia 2, MIM# 613610; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Craniosynostosis v1.8 SMO Zornitza Stark Phenotypes for gene: SMO were changed from Curry-Jones syndrome to Curry-Jones syndrome, somatic mosaic, MIM# 601707
Craniosynostosis v1.7 SMO Zornitza Stark reviewed gene: SMO: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Curry-Jones syndrome, somatic mosaic, MIM# 601707; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v1.7 SMAD6 Zornitza Stark Phenotypes for gene: SMAD6 were changed from non-syndromic craniosynostosis to {Craniosynostosis 7, susceptibility to}, MIM# 617439
Craniosynostosis v1.6 SMAD6 Zornitza Stark reviewed gene: SMAD6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: {Craniosynostosis 7, susceptibility to}, MIM# 617439; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v1.6 SKI Zornitza Stark Phenotypes for gene: SKI were changed from SHPRINTZEN-GOLDBERG CRANIOSYNOSTOSIS SYNDROME to Shprintzen-Goldberg syndrome, MIM# 182212
Craniosynostosis v1.5 SKI Zornitza Stark reviewed gene: SKI: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Shprintzen-Goldberg syndrome, MIM# 182212; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v1.5 MEGF8 Zornitza Stark Phenotypes for gene: MEGF8 were changed from Carpenter syndrome to Carpenter syndrome, MIM#614976
Craniosynostosis v1.4 MEGF8 Zornitza Stark reviewed gene: MEGF8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Carpenter syndrome, MIM#614976; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Craniosynostosis v1.4 MASP1 Zornitza Stark Phenotypes for gene: MASP1 were changed from 3MC syndrome to 3MC syndrome, MIM#257920
Craniosynostosis v1.3 MASP1 Zornitza Stark reviewed gene: MASP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: 3MC syndrome, MIM#257920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Craniosynostosis v1.3 KAT6A Zornitza Stark Phenotypes for gene: KAT6A were changed from Arboleda-Tham syndrome to Arboleda-Tham syndrome, MIM#616268
Craniosynostosis v1.2 KAT6A Zornitza Stark reviewed gene: KAT6A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Arboleda-Tham syndrome, MIM#616268; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v1.2 HNRNPK Zornitza Stark Phenotypes for gene: HNRNPK were changed from Au-Kline syndrome to Au-Kline syndrome, MIM#616580
Craniosynostosis v1.1 HNRNPK Zornitza Stark reviewed gene: HNRNPK: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Au-Kline syndrome, MIM#616580; Mode of inheritance: None
Mackenzie's Mission_Reproductive Carrier Screening v0.32 GALT Sarah Righetti changed review comment from: Now included in all states for consistency. Treatable but can still be signficant speech problems and long-term neurological issues - treatment only resolves liver phenotype.; to: Not included on NBS in Victoria, included in all three states for consistency.

Treatable but can still be signficant speech problems and long-term neurological issues - treatment only resolves liver phenotype.
Mackenzie's Mission_Reproductive Carrier Screening v0.32 GALT Sarah Righetti reviewed gene: GALT: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Galactosaemia, MIM #230400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mackenzie's Mission_Reproductive Carrier Screening v0.32 ERBB3 Sarah Righetti reviewed gene: ERBB3: Rating: GREEN; Mode of pathogenicity: None; Publications: 17701904, 31752936, 28454995; Phenotypes: Lethal congenital contractural syndrome 3, MIM# 611369; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mackenzie's Mission_Reproductive Carrier Screening v0.32 ERBB3 Sarah Righetti Deleted their review
Mackenzie's Mission_Reproductive Carrier Screening v0.32 ERBB3 Sarah Righetti reviewed gene: ERBB3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: 17701904, 31752936; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mackenzie's Mission_Reproductive Carrier Screening v0.32 TUBA8 Sarah Righetti reviewed gene: TUBA8: Rating: RED; Mode of pathogenicity: None; Publications: 19896110, 31481326, 28388629; Phenotypes: Cortical dysplasia, complex, with other brain malformations 8, MIM# 613180; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mackenzie's Mission_Reproductive Carrier Screening v0.32 TUBA8 Sarah Righetti Deleted their review
Mackenzie's Mission_Reproductive Carrier Screening v0.32 TUBA8 Sarah Righetti reviewed gene: TUBA8: Rating: ; Mode of pathogenicity: None; Publications: 19896110, 31481326, 28388629; Phenotypes: Cortical dysplasia, complex, with other brain malformations 8, MIM #613180; Mode of inheritance: None
Mackenzie's Mission_Reproductive Carrier Screening v0.32 TSPYL1 Sarah Righetti 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
Mackenzie's Mission_Reproductive Carrier Screening v0.32 PIP5K1C Sarah Righetti 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
Intellectual disability syndromic and non-syndromic v0.3099 DPH1 Zornitza Stark Publications for gene: DPH1 were set to 25558065; 26220823
Intellectual disability syndromic and non-syndromic v0.3098 DPH1 Zornitza Stark edited their review of gene: DPH1: Added comment: Four unrelated families reported, 11 affected individuals. Common clinical features include abnormal skull shape (trigonocephaly, scaphocephaly, or prominent forehead accompanied with metopic ridge), distinctive face (downslanted palpebral fissures, low set ears, depressed nasal bridge, and sparse hair on the scalp, eyelashes, and/or eyebrows), short stature, developmental delay, and intellectual disability. Heart and brain malformations are also frequently observed.; Changed publications: 29362492, 29410513, 25558065, 26220823
Mendeliome v0.5072 DPH1 Zornitza Stark Marked gene: DPH1 as ready
Mendeliome v0.5072 DPH1 Zornitza Stark Gene: dph1 has been classified as Green List (High Evidence).
Mendeliome v0.5072 DPH1 Zornitza Stark Phenotypes for gene: DPH1 were changed from to Developmental delay with short stature, dysmorphic facial features, and sparse hair, MIM# 616901
Mendeliome v0.5071 DPH1 Zornitza Stark Publications for gene: DPH1 were set to
Mendeliome v0.5070 DPH1 Zornitza Stark Mode of inheritance for gene: DPH1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5069 DPH1 Zornitza Stark edited their review of gene: DPH1: Changed publications: 29362492, 29410513, 25558065, 26220823
Mendeliome v0.5069 DPH1 Zornitza Stark reviewed gene: DPH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29362492, 29410513, 25558065, 26220823]; Phenotypes: Developmental delay with short stature, dysmorphic facial features, and sparse hair, MIM# 616901; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Craniosynostosis v1.1 FGF10 Zornitza Stark Phenotypes for gene: FGF10 were changed from to Craniosynostosis
Craniosynostosis v1.0 FGF10 Zornitza Stark edited their review of gene: FGF10: Changed phenotypes: Craniosynostosis
Mendeliome v0.5069 PTCD3 Zornitza Stark Phenotypes for gene: PTCD3 were changed from Intellectual disability; optic atrophy; Leigh-like syndrome to Combined oxidative phosphorylation deficiency-51, MIM#619057; Intellectual disability; optic atrophy; Leigh-like syndrome
Mendeliome v0.5068 PTCD3 Zornitza Stark edited their review of gene: PTCD3: Changed phenotypes: Combined oxidative phosphorylation deficiency-51, MIM#619057, Intellectual disability, optic atrophy, Leigh-like syndrome
Mitochondrial disease v0.517 PTCD3 Zornitza Stark Phenotypes for gene: PTCD3 were changed from Mental retardation; optic atrophy; Leigh-like syndrome to Combined oxidative phosphorylation deficiency-51, MIM#619057; Mental retardation; optic atrophy; Leigh-like syndrome
Mitochondrial disease v0.516 PTCD3 Zornitza Stark reviewed gene: PTCD3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Combined oxidative phosphorylation deficiency-51, MIM#619057; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5068 LRP8 Bryony Thompson Marked gene: LRP8 as ready
Mendeliome v0.5068 LRP8 Bryony Thompson Gene: lrp8 has been classified as Red List (Low Evidence).
Mendeliome v0.5068 LRP8 Bryony Thompson Classified gene: LRP8 as Red List (low evidence)
Mendeliome v0.5068 LRP8 Bryony Thompson Gene: lrp8 has been classified as Red List (Low Evidence).
Mendeliome v0.5067 LRP8 Bryony Thompson reviewed gene: LRP8: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Myocardial infarction, susceptibility to MIM#608446; Mode of inheritance: Unknown
Mendeliome v0.5067 TCF21 Bryony Thompson Marked gene: TCF21 as ready
Mendeliome v0.5067 TCF21 Bryony Thompson Gene: tcf21 has been classified as Red List (Low Evidence).
Mendeliome v0.5067 TCF21 Bryony Thompson Classified gene: TCF21 as Red List (low evidence)
Mendeliome v0.5067 TCF21 Bryony Thompson Gene: tcf21 has been classified as Red List (Low Evidence).
Mendeliome v0.5066 TCF21 Bryony Thompson reviewed gene: TCF21: Rating: RED; Mode of pathogenicity: None; Publications: 16156022, 10769282, 24875298; Phenotypes: Sensorineural hearing loss, dilated cardiomyopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Retinal Disorders Superpanel v1.153 Zornitza Stark Panel name changed from Retinal Disorders to Retinal Disorders Superpanel
Genetic Epilepsy v0.886 SETD1A Zornitza Stark Phenotypes for gene: SETD1A were changed from Epilepsy to Epilepsy, early-onset, with or without developmental delay, MIM# 618832; Neurodevelopmental disorder with speech impairment and dysmorphic facies, MIM# 619056
Genetic Epilepsy v0.885 SETD1A Zornitza Stark Publications for gene: SETD1A were set to 31197650
Mendeliome v0.5066 SETD1A Zornitza Stark changed review comment from: OMIM has assigned a second phenotype in relation to the syndromic ID cohort reported in PMID 32346159. All variants were predicted to disrupt or delete the SET catalytic domain, and LOF is the established mechanism.

In addition, there are 3 families reported with a predominantly seizure phenotype without ID, PMID 31197650. All the variants are missense and mechanism of pathogenicity is not clearly established, hence it is difficult to know whether these are two distinct conditions or part of a spectrum of severity for SETD1A-related disorders.; to: OMIM has assigned a second phenotype in relation to the syndromic ID cohort reported in PMID 32346159. All variants were predicted to disrupt or delete the SET catalytic domain, and LOF is the established mechanism.

In addition, there are 4 families reported with a predominantly seizure phenotype without ID, PMID 31197650. All the variants are missense and mechanism of pathogenicity is not clearly established, hence it is difficult to know whether these are two distinct conditions or part of a spectrum of severity for SETD1A-related disorders.
Intellectual disability syndromic and non-syndromic v0.3098 SETD1A Zornitza Stark changed review comment from: OMIM has assigned a second phenotype in relation to the syndromic ID cohort reported in PMID 32346159. All variants were predicted to disrupt or delete the SET catalytic domain, and LOF is the established mechanism.

In addition, there are 3 families reported with a predominantly seizure phenotype without ID, PMID 31197650. All the variants are missense and mechanism of pathogenicity is not clearly established, hence it is difficult to know whether these are two distinct conditions or part of a spectrum of severity for SETD1A-related disorders.; to: OMIM has assigned a second phenotype in relation to the syndromic ID cohort reported in PMID 32346159. All variants were predicted to disrupt or delete the SET catalytic domain, and LOF is the established mechanism.

In addition, there are 4 families reported with a predominantly seizure phenotype without ID, PMID 31197650. All the variants are missense and mechanism of pathogenicity is not clearly established, hence it is difficult to know whether these are two distinct conditions or part of a spectrum of severity for SETD1A-related disorders.
Genetic Epilepsy v0.884 SETD1A Zornitza Stark edited their review of gene: SETD1A: Added comment: OMIM has assigned a second phenotype in relation to the syndromic ID cohort reported in PMID 32346159. All variants were predicted to disrupt or delete the SET catalytic domain, and LOF is the established mechanism.

In addition, there are 4 families reported with a predominantly seizure phenotype without ID, PMID 31197650. All the variants are missense and mechanism of pathogenicity is not clearly established, hence it is difficult to know whether these are two distinct conditions or part of a spectrum of severity for SETD1A-related disorders.; Changed phenotypes: Epilepsy, early-onset, with or without developmental delay, MIM# 618832, Neurodevelopmental disorder with speech impairment and dysmorphic facies, MIM# 619056
Genetic Epilepsy v0.884 SETD1A Zornitza Stark changed review comment from: Four unrelated families reported: in three, the variants occurred de novo, and in the fourth, it segregated with disease. Some functional data.
Sources: Literature; to: PMID: 31197650. Four unrelated families reported: in three, the variants occurred de novo, and in the fourth, it segregated with disease. Some functional data.
Sources: Literature
Mendeliome v0.5066 SETD1A Zornitza Stark Phenotypes for gene: SETD1A were changed from Epilepsy, early-onset, with or without developmental delay, MIM# 618832 to Epilepsy, early-onset, with or without developmental delay, MIM# 618832; Neurodevelopmental disorder with speech impairment and dysmorphic facies, MIM# 619056
Mendeliome v0.5065 SETD1A Zornitza Stark edited their review of gene: SETD1A: Added comment: OMIM has assigned a second phenotype in relation to the syndromic ID cohort reported in PMID 32346159. All variants were predicted to disrupt or delete the SET catalytic domain, and LOF is the established mechanism.

In addition, there are 3 families reported with a predominantly seizure phenotype without ID, PMID 31197650. All the variants are missense and mechanism of pathogenicity is not clearly established, hence it is difficult to know whether these are two distinct conditions or part of a spectrum of severity for SETD1A-related disorders.; Changed phenotypes: Epilepsy, early-onset, with or without developmental delay, MIM# 618832, Neurodevelopmental disorder with speech impairment and dysmorphic facies, MIM# 619056
Intellectual disability syndromic and non-syndromic v0.3098 SETD1A Zornitza Stark Phenotypes for gene: SETD1A were changed from Epilepsy, early-onset, with or without developmental delay, MIM# 618832 to Epilepsy, early-onset, with or without developmental delay, MIM# 618832; Neurodevelopmental disorder with speech impairment and dysmorphic facies, MIM# 619056
Intellectual disability syndromic and non-syndromic v0.3097 SETD1A Zornitza Stark edited their review of gene: SETD1A: Added comment: OMIM has assigned a second phenotype in relation to the syndromic ID cohort reported in PMID 32346159. All variants were predicted to disrupt or delete the SET catalytic domain, and LOF is the established mechanism.

In addition, there are 3 families reported with a predominantly seizure phenotype without ID, PMID 31197650. All the variants are missense and mechanism of pathogenicity is not clearly established, hence it is difficult to know whether these are two distinct conditions or part of a spectrum of severity for SETD1A-related disorders.; Changed phenotypes: Epilepsy, early-onset, with or without developmental delay, MIM# 618832, Neurodevelopmental disorder with speech impairment and dysmorphic facies, MIM# 619056
Mendeliome v0.5065 JARID2 Zornitza Stark Publications for gene: JARID2 were set to 23294540
Mendeliome v0.5064 JARID2 Zornitza Stark Classified gene: JARID2 as Green List (high evidence)
Mendeliome v0.5064 JARID2 Zornitza Stark Gene: jarid2 has been classified as Green List (High Evidence).
Mendeliome v0.5063 JARID2 Zornitza Stark edited their review of gene: JARID2: Added comment: 13 additional individuals reported, note CNVs common but LOF sequence variants identified too.; Changed rating: GREEN; Changed publications: 23294540, 33077894
Intellectual disability syndromic and non-syndromic v0.3097 JARID2 Zornitza Stark Publications for gene: JARID2 were set to 23294540
Intellectual disability syndromic and non-syndromic v0.3096 JARID2 Zornitza Stark Tag SV/CNV tag was added to gene: JARID2.
Intellectual disability syndromic and non-syndromic v0.3096 JARID2 Zornitza Stark Classified gene: JARID2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3096 JARID2 Zornitza Stark Gene: jarid2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3095 JARID2 Zornitza Stark changed review comment from: 13 additional individuals reported, note CNVs common.; to: 13 additional individuals reported, note CNVs common but LOF sequence variants identified too.
Intellectual disability syndromic and non-syndromic v0.3095 JARID2 Zornitza Stark edited their review of gene: JARID2: Added comment: 13 additional individuals reported, note CNVs common.; Changed rating: GREEN; Changed publications: 23294540, 33077894
Mendeliome v0.5063 NUDT2 Zornitza Stark Phenotypes for gene: NUDT2 were changed from Muscular hypotonia; Global developmental delay; Intellectual disability to Muscular hypotonia; Global developmental delay; Intellectual disability; Polyneuropathy
Mendeliome v0.5062 NUDT2 Zornitza Stark Publications for gene: NUDT2 were set to 27431290; 30059600
Mendeliome v0.5061 NUDT2 Zornitza Stark Classified gene: NUDT2 as Green List (high evidence)
Mendeliome v0.5061 NUDT2 Zornitza Stark Gene: nudt2 has been classified as Green List (High Evidence).
Mendeliome v0.5060 NUDT2 Zornitza Stark edited their review of gene: NUDT2: Added comment: Three individuals from two additional families reported with a different homozygous variant and ID/polyneuropathy phenotype. Upgrade to Green.; Changed rating: GREEN; Changed publications: 27431290, 30059600, 33058507
Intellectual disability syndromic and non-syndromic v0.3095 NUDT2 Zornitza Stark Phenotypes for gene: NUDT2 were changed from Muscular hypotonia; Global developmental delay; Intellectual disability to Muscular hypotonia; Global developmental delay; Intellectual disability; Polyneuropathy
Intellectual disability syndromic and non-syndromic v0.3094 NUDT2 Zornitza Stark Publications for gene: NUDT2 were set to 27431290; 30059600
Intellectual disability syndromic and non-syndromic v0.3093 NUDT2 Zornitza Stark Classified gene: NUDT2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3093 NUDT2 Zornitza Stark Gene: nudt2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3092 NUDT2 Zornitza Stark changed review comment from: Two additional families reported with a different homozygous variant and ID/polyneuropathy phenotype. Upgrade to Green.; to: Three individuals from two additional families reported with a different homozygous variant and ID/polyneuropathy phenotype. Upgrade to Green.
Intellectual disability syndromic and non-syndromic v0.3092 NUDT2 Zornitza Stark edited their review of gene: NUDT2: Added comment: Two additional families reported with a different homozygous variant and ID/polyneuropathy phenotype. Upgrade to Green.; Changed rating: GREEN; Changed publications: 27431290, 30059600, 33058507; Changed phenotypes: Muscular hypotonia, Global developmental delay, Intellectual disability, Polyneuropathy
Mendeliome v0.5060 AFF2 Zornitza Stark changed review comment from: This is classically a triplet expansion disorder. Note one report of an intragenic deletion which segregated with ID in a family, and two truncating variants classified as pathogenic by laboratories in ClinVar.; to: This is classically a triplet expansion disorder. Note one report of an intragenic deletion which segregated with ID in a family, and two truncating variants classified as pathogenic by laboratories in ClinVar. Missense variants found to be over-represented in an autism cohort.
Mendeliome v0.5060 AFF2 Zornitza Stark edited their review of gene: AFF2: Changed publications: 8334699, 21739600, 22773736
Intellectual disability syndromic and non-syndromic v0.3092 AFF2 Zornitza Stark Marked gene: AFF2 as ready
Intellectual disability syndromic and non-syndromic v0.3092 AFF2 Zornitza Stark Gene: aff2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3092 AFF2 Zornitza Stark Phenotypes for gene: AFF2 were changed from to Mental retardation, X-linked, FRAXE type 309548
Intellectual disability syndromic and non-syndromic v0.3091 AFF2 Zornitza Stark Publications for gene: AFF2 were set to
Intellectual disability syndromic and non-syndromic v0.3090 AFF2 Zornitza Stark Mode of inheritance for gene: AFF2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3089 AFF2 Zornitza Stark reviewed gene: AFF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 8334699, 21739600, 22773736; Phenotypes: Mental retardation, X-linked, FRAXE type 309548; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5060 AFF2 Zornitza Stark Tag SV/CNV tag was added to gene: AFF2.
Tag STR tag was added to gene: AFF2.
Mendeliome v0.5060 AFF2 Zornitza Stark Marked gene: AFF2 as ready
Mendeliome v0.5060 AFF2 Zornitza Stark Gene: aff2 has been classified as Green List (High Evidence).
Mendeliome v0.5060 AFF2 Zornitza Stark Phenotypes for gene: AFF2 were changed from to Mental retardation, X-linked, FRAXE type 309548
Mendeliome v0.5059 AFF2 Zornitza Stark Publications for gene: AFF2 were set to
Mendeliome v0.5058 AFF2 Zornitza Stark Mode of inheritance for gene: AFF2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5057 AFF2 Zornitza Stark commented on gene: AFF2: This is classically a triplet expansion disorder. Note one report of an intragenic deletion which segregated with ID in a family, and two truncating variants classified as pathogenic by laboratories in ClinVar.
Mendeliome v0.5057 AFF2 Zornitza Stark reviewed gene: AFF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 8334699, 21739600; Phenotypes: Mental retardation, X-linked, FRAXE type 309548; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mackenzie's Mission_Reproductive Carrier Screening v0.32 AFF2 Sarah Righetti gene: AFF2 was added
gene: AFF2 was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Expert Review
Mode of inheritance for gene: AFF2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: AFF2 were set to Mental retardation, X-linked, FRAXE type, #309548
Added comment: Mechanism of disease is triplet repeat expansion. FRAXE less severe and much rarer than FRAXA. Excluded from MM screening panel on technical grounds.
Sources: Expert Review
Aortopathy_Connective Tissue Disorders v1.3 ATP6V1E1 Zornitza Stark Marked gene: ATP6V1E1 as ready
Aortopathy_Connective Tissue Disorders v1.3 ATP6V1E1 Zornitza Stark Gene: atp6v1e1 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.78 KANSL1 Zornitza Stark Tag SV/CNV tag was added to gene: KANSL1.
Intellectual disability syndromic and non-syndromic v0.3089 KANSL1 Zornitza Stark Tag SV/CNV tag was added to gene: KANSL1.
Intellectual disability syndromic and non-syndromic v0.3089 AUTS2 Zornitza Stark Marked gene: AUTS2 as ready
Intellectual disability syndromic and non-syndromic v0.3089 AUTS2 Zornitza Stark Gene: auts2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3089 AUTS2 Zornitza Stark Phenotypes for gene: AUTS2 were changed from to Mental retardation, autosomal dominant 26, MIM#615834
Intellectual disability syndromic and non-syndromic v0.3088 AUTS2 Zornitza Stark Publications for gene: AUTS2 were set to
Mendeliome v0.5057 AUTS2 Zornitza Stark Marked gene: AUTS2 as ready
Mendeliome v0.5057 AUTS2 Zornitza Stark Gene: auts2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3087 AUTS2 Zornitza Stark Mode of inheritance for gene: AUTS2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3086 AUTS2 Zornitza Stark Tag SV/CNV tag was added to gene: AUTS2.
Intellectual disability syndromic and non-syndromic v0.3086 AUTS2 Zornitza Stark reviewed gene: AUTS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23332918, 25205402, 31474318; Phenotypes: Mental retardation, autosomal dominant 26, MIM#615834; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5057 AUTS2 Zornitza Stark Phenotypes for gene: AUTS2 were changed from to Mental retardation, autosomal dominant 26, MIM#615834
Mendeliome v0.5056 AUTS2 Zornitza Stark Publications for gene: AUTS2 were set to
Mendeliome v0.5055 AUTS2 Zornitza Stark Mode of inheritance for gene: AUTS2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5055 AUTS2 Zornitza Stark Mode of inheritance for gene: AUTS2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5054 AUTS2 Zornitza Stark Tag SV/CNV tag was added to gene: AUTS2.
Mendeliome v0.5054 AUTS2 Zornitza Stark reviewed gene: AUTS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23332918, 25205402, 31474318; Phenotypes: Mental retardation, autosomal dominant 26, MIM#615834; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3086 ZEB2 Zornitza Stark Marked gene: ZEB2 as ready
Intellectual disability syndromic and non-syndromic v0.3086 ZEB2 Zornitza Stark Gene: zeb2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3086 ZEB2 Zornitza Stark Phenotypes for gene: ZEB2 were changed from to Mowat-Wilson syndrome (MIM#235730)
Intellectual disability syndromic and non-syndromic v0.3085 ZEB2 Zornitza Stark Publications for gene: ZEB2 were set to
Intellectual disability syndromic and non-syndromic v0.3084 ZEB2 Zornitza Stark Mode of inheritance for gene: ZEB2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3083 ZEB2 Zornitza Stark reviewed gene: ZEB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29300384; Phenotypes: Mowat-Wilson syndrome (MIM#235730); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.494 ZEB2 Zornitza Stark Marked gene: ZEB2 as ready
Microcephaly v0.494 ZEB2 Zornitza Stark Gene: zeb2 has been classified as Green List (High Evidence).
Microcephaly v0.494 ZEB2 Zornitza Stark Phenotypes for gene: ZEB2 were changed from to Mowat-Wilson syndrome (MIM#235730)
Microcephaly v0.493 ZEB2 Zornitza Stark Publications for gene: ZEB2 were set to
Microcephaly v0.492 ZEB2 Zornitza Stark Mode of inheritance for gene: ZEB2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.491 ZEB2 Zornitza Stark reviewed gene: ZEB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29300384; Phenotypes: Mowat-Wilson syndrome (MIM#235730); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hirschsprung disease v0.10 ZEB2 Zornitza Stark Marked gene: ZEB2 as ready
Hirschsprung disease v0.10 ZEB2 Zornitza Stark Gene: zeb2 has been classified as Green List (High Evidence).
Hirschsprung disease v0.10 ZEB2 Zornitza Stark Phenotypes for gene: ZEB2 were changed from to Mowat-Wilson syndrome (MIM#235730)
Hirschsprung disease v0.9 ZEB2 Zornitza Stark Publications for gene: ZEB2 were set to
Hirschsprung disease v0.8 ZEB2 Zornitza Stark Mode of inheritance for gene: ZEB2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hirschsprung disease v0.7 ZEB2 Zornitza Stark reviewed gene: ZEB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29300384; Phenotypes: Mowat-Wilson syndrome (MIM#235730); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5054 ZEB2 Zornitza Stark Phenotypes for gene: ZEB2 were changed from to Mowat-Wilson syndrome (MIM#235730)
Mendeliome v0.5053 ZEB2 Zornitza Stark Publications for gene: ZEB2 were set to
Mendeliome v0.5052 ZEB2 Zornitza Stark Mode of inheritance for gene: ZEB2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Proteinuria v0.140 ITSN2 Zornitza Stark Marked gene: ITSN2 as ready
Proteinuria v0.140 ITSN2 Zornitza Stark Gene: itsn2 has been classified as Green List (High Evidence).
Proteinuria v0.140 ITSN2 Zornitza Stark Classified gene: ITSN2 as Green List (high evidence)
Proteinuria v0.140 ITSN2 Zornitza Stark Gene: itsn2 has been classified as Green List (High Evidence).
Mendeliome v0.5051 ITSN2 Zornitza Stark Marked gene: ITSN2 as ready
Mendeliome v0.5051 ITSN2 Zornitza Stark Gene: itsn2 has been classified as Green List (High Evidence).
Mendeliome v0.5051 ITSN2 Zornitza Stark Classified gene: ITSN2 as Green List (high evidence)
Mendeliome v0.5051 ITSN2 Zornitza Stark Gene: itsn2 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.78 KANSL1 Zornitza Stark Marked gene: KANSL1 as ready
Congenital Heart Defect v0.78 KANSL1 Zornitza Stark Gene: kansl1 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.78 KANSL1 Zornitza Stark Phenotypes for gene: KANSL1 were changed from to Koolen-De Vries syndrome, MIM# 610443
Congenital Heart Defect v0.77 KANSL1 Zornitza Stark Publications for gene: KANSL1 were set to
Congenital Heart Defect v0.76 KANSL1 Zornitza Stark Mode of inheritance for gene: KANSL1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.75 KANSL1 Zornitza Stark reviewed gene: KANSL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26306646; Phenotypes: Koolen-De Vries syndrome, MIM# 610443; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.75 TAF1 Zornitza Stark Marked gene: TAF1 as ready
Congenital Heart Defect v0.75 TAF1 Zornitza Stark Gene: taf1 has been classified as Amber List (Moderate Evidence).
Congenital Heart Defect v0.75 TAF1 Zornitza Stark Phenotypes for gene: TAF1 were changed from Dystonia-Parkinsonism, X-linked 314250; Mental retardation, X-linked, syndromic 33 300966; congenital cardiac disease and global developmental delay to Mental retardation, X-linked, syndromic 33 300966; congenital cardiac disease and global developmental delay
Congenital Heart Defect v0.74 TAF1 Zornitza Stark Classified gene: TAF1 as Amber List (moderate evidence)
Congenital Heart Defect v0.74 TAF1 Zornitza Stark Gene: taf1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5050 ZEB2 Ain Roesley reviewed gene: ZEB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29300384; Phenotypes: Mowat-Wilson syndrome (MIM#235730); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Proteinuria v0.139 ITSN2 Elena Savva gene: ITSN2 was added
gene: ITSN2 was added to Proteinuria. Sources: Literature
Mode of inheritance for gene: ITSN2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ITSN2 were set to PMID: 29773874
Phenotypes for gene: ITSN2 were set to Nephrotic syndrome
Review for gene: ITSN2 was set to GREEN
Added comment: PMID: 29773874: 2 families (3 patients) with homozygous missense or chet missense/PTC + null mice recapitulating the human phenotype.
Functional analysis of all variants shows an inability for Cdc42 activation as shown by wildtype overexpression
Sources: Literature
Mendeliome v0.5050 ITSN2 Elena Savva gene: ITSN2 was added
gene: ITSN2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ITSN2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ITSN2 were set to PMID: 29773874
Phenotypes for gene: ITSN2 were set to Nephrotic syndrome
Review for gene: ITSN2 was set to GREEN
Added comment: PMID: 29773874: 2 families (3 patients) with homozygous missense or chet missense/PTC + null mice recapitulating the human phenotype.
Functional analysis of all variants shows an inability for Cdc42 activation as shown by wildtype overexpression
Sources: Literature
Congenital Heart Defect v0.73 TAF1 Elena Savva gene: TAF1 was added
gene: TAF1 was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: TAF1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: TAF1 were set to PMID: 32396742; 31646703; 26637982; 31341187
Phenotypes for gene: TAF1 were set to Dystonia-Parkinsonism, X-linked 314250; Mental retardation, X-linked, syndromic 33 300966; congenital cardiac disease and global developmental delay
Review for gene: TAF1 was set to AMBER
Added comment: -Carrier females consistently shown to be asymptomatic with skewed X-inactivation
-While no PTCs have been reported, the lack of representation in population databases strongly suggests these mutations are not compatible with life (Gudmundsson, S. et al. (2019))

Two patients with hemizygous missense variants, with congenital cardiac disease and global developmental delay
Sources: Literature
Cerebellar and Pontocerebellar Hypoplasia v0.152 AUTS2 Zornitza Stark Publications for gene: AUTS2 were set to 17211639; 27075013; 22872102
Cerebellar and Pontocerebellar Hypoplasia v0.151 AUTS2 Zornitza Stark Classified gene: AUTS2 as Amber List (moderate evidence)
Cerebellar and Pontocerebellar Hypoplasia v0.151 AUTS2 Zornitza Stark Gene: auts2 has been classified as Amber List (Moderate Evidence).
Cerebellar and Pontocerebellar Hypoplasia v0.150 AUTS2 Elena Savva edited their review of gene: AUTS2: Added comment: aka KIAA0442

PMID: 17211639 - 5 patients (4 families) with translocation rearrangements resulting in truncated AUTS2. 1/5 patients has a hypoplastic brain stem, 2/5 (both twins) show cerebral atrophy. Remaining 2/5 patients did not have an MRI. All patients were <18 years old.

PMID: 27075013 - describes 13 patients with CNVs in the AUTS2 gene. Report "An MRI was done in eight patients. None had structural brain malformations except for a stable arachnoidal cyst in one."

PMID: 22872102 - describes 4 patients with CNVs in AUTS2. Only 2/4 had an MRI, both regarded as "normal", patients were aged 10 and 3 yo.

PMID: 31474318 - 4 patients with de novo inframe deletions, frameshift and missense variants. Patients are from a cohort with either Dandy-Walker malformations or cerebellar hypoplasia; Changed publications: PMID: 17211639, 27075013, 22872102, 31474318
Mendeliome v0.5050 PI4K2A Zornitza Stark Marked gene: PI4K2A as ready
Mendeliome v0.5050 PI4K2A Zornitza Stark Gene: pi4k2a has been classified as Red List (Low Evidence).
Mendeliome v0.5050 PI4K2A Zornitza Stark gene: PI4K2A was added
gene: PI4K2A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PI4K2A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PI4K2A were set to 32418222
Phenotypes for gene: PI4K2A were set to Cutis laxa, intellectual disability, movement disorder
Review for gene: PI4K2A was set to RED
Added comment: Single individual reported with homozygous missense variant and functional data including mouse model.
Sources: Literature
Aortopathy_Connective Tissue Disorders v1.3 PI4K2A Zornitza Stark Marked gene: PI4K2A as ready
Aortopathy_Connective Tissue Disorders v1.3 PI4K2A Zornitza Stark Gene: pi4k2a has been classified as Red List (Low Evidence).
Aortopathy_Connective Tissue Disorders v1.3 PI4K2A Zornitza Stark gene: PI4K2A was added
gene: PI4K2A was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: PI4K2A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PI4K2A were set to 32418222
Phenotypes for gene: PI4K2A were set to Cutis laxa, intellectual disability, movement disorder
Review for gene: PI4K2A was set to RED
Added comment: Single individual reported with homozygous missense variant and functional data including mouse model.
Sources: Literature
Mendeliome v0.5049 NR5A1 Zornitza Stark Marked gene: NR5A1 as ready
Mendeliome v0.5049 NR5A1 Zornitza Stark Gene: nr5a1 has been classified as Green List (High Evidence).
Mendeliome v0.5049 NR5A1 Zornitza Stark Phenotypes for gene: NR5A1 were changed from to Adrenocortical insufficiency, (MIM#612964); 46, XX sex reversal 4, (MIM# 617480); Premature ovarian failure 7, (MIM#612964); Spermatogenic failure 8, (MIM#613957); 46XY sex reversal 3, (MIM#612965)
Mendeliome v0.5048 NR5A1 Zornitza Stark Publications for gene: NR5A1 were set to
Mendeliome v0.5047 NR5A1 Zornitza Stark Mode of inheritance for gene: NR5A1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5046 NR5A1 Zornitza Stark reviewed gene: NR5A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31513305; Phenotypes: Adrenocortical insufficiency, (MIM#612964), 46, XX sex reversal 4, (MIM# 617480), Premature ovarian failure 7, (MIM#612964), Spermatogenic failure 8, (MIM#613957), 46XY sex reversal 3, (MIM#612965); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.175 NR5A1 Zornitza Stark Marked gene: NR5A1 as ready
Differences of Sex Development v0.175 NR5A1 Zornitza Stark Gene: nr5a1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.175 NR5A1 Zornitza Stark Phenotypes for gene: NR5A1 were changed from to Adrenocortical insufficiency, (MIM#612964); 46, XX sex reversal 4, (MIM# 617480); Premature ovarian failure 7, (MIM#612964); Spermatogenic failure 8, (MIM#613957); 46XY sex reversal 3, (MIM#612965)
Differences of Sex Development v0.174 NR5A1 Zornitza Stark Publications for gene: NR5A1 were set to
Differences of Sex Development v0.173 NR5A1 Zornitza Stark Mode of inheritance for gene: NR5A1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v1.2 ZNF469 Zornitza Stark Phenotypes for gene: ZNF469 were changed from Brittle cornea syndrome 1 to Brittle cornea syndrome 1,MIM# 229200
Aortopathy_Connective Tissue Disorders v1.1 ROBO4 Zornitza Stark Phenotypes for gene: ROBO4 were changed from bicuspid aortic valve; ascending aortic aneurysm; ascending aorta dilatation to Aortic valve disease 8, MIM# 618496; bicuspid aortic valve; ascending aortic aneurysm; ascending aorta dilatation
Aortopathy_Connective Tissue Disorders v1.0 ROBO4 Zornitza Stark edited their review of gene: ROBO4: Added comment: Two families plus segregation and functional data including animal model.; Changed publications: 30455415
Aortopathy_Connective Tissue Disorders v1.0 ROBO4 Zornitza Stark reviewed gene: ROBO4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Aortic valve disease 8, MIM# 618496; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.172 NR5A1 Ain Roesley edited their review of gene: NR5A1: Added comment: 188 variants from 238 cases. No genotype-phenotype correlation establised; Changed phenotypes: Adrenocortical insufficiency, (MIM#612964), 46, XX sex reversal 4, (MIM# 617480), Premature ovarian failure 7, (MIM#612964), Spermatogenic failure 8, (MIM#613957), 46XY sex reversal 3, (MIM#612965)
Differences of Sex Development v0.172 NR5A1 Ain Roesley reviewed gene: NR5A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31513305; Phenotypes: Adrenocortical insufficiency, (MIM#612964), 46, XX sex reversal 4, (MIM# 617480), Premature ovarian failure 7, (MIM#612964), Spermatogenic failure 8, (MIM#613957), 46XY sex reversal 3, (MIM#612965), Autosomal dominant; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hirschsprung disease v0.7 EDN3 Zornitza Stark Marked gene: EDN3 as ready
Hirschsprung disease v0.7 EDN3 Zornitza Stark Gene: edn3 has been classified as Green List (High Evidence).
Hirschsprung disease v0.7 EDN3 Zornitza Stark Phenotypes for gene: EDN3 were changed from to Central hypoventilation syndrome, congenital, MIM# 209880; Waardenburg syndrome, type 4B, MIM# 613265; {Hirschsprung disease, susceptibility to, 4}, MIM# 613712
Hirschsprung disease v0.6 EDN3 Zornitza Stark Publications for gene: EDN3 were set to
Hirschsprung disease v0.5 EDN3 Zornitza Stark Mode of inheritance for gene: EDN3 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hirschsprung disease v0.4 EDN3 Zornitza Stark reviewed gene: EDN3: Rating: GREEN; Mode of pathogenicity: None; Publications: 8630502, 11303518, 9359047, 10231870, 30171849, 27370713; Phenotypes: Central hypoventilation syndrome, congenital, MIM# 209880, Waardenburg syndrome, type 4B, MIM# 613265, {Hirschsprung disease, susceptibility to, 4}, MIM# 613712; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3083 HECW2 Zornitza Stark Publications for gene: HECW2 were set to 27389779
Intellectual disability syndromic and non-syndromic v0.3082 HECW2 Zornitza Stark Mode of pathogenicity for gene: HECW2 was changed from to Other
Intellectual disability syndromic and non-syndromic v0.3081 HECW2 Zornitza Stark reviewed gene: HECW2: Rating: GREEN; Mode of pathogenicity: Other; Publications: 29807643, 29395664, 27334371, 27389779; Phenotypes: Neurodevelopmental disorder with hypotonia, seizures, and absent language, MIM# 617268, intellectual disability, epilepsy, regression, microcephaly; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.884 HECW2 Zornitza Stark Marked gene: HECW2 as ready
Genetic Epilepsy v0.884 HECW2 Zornitza Stark Gene: hecw2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.884 HECW2 Zornitza Stark Phenotypes for gene: HECW2 were changed from to Neurodevelopmental disorder with hypotonia, seizures, and absent language, MIM# 617268; intellectual disability; epilepsy; regression; microcephaly
Genetic Epilepsy v0.883 HECW2 Zornitza Stark Mode of pathogenicity for gene: HECW2 was changed from to Other
Genetic Epilepsy v0.882 HECW2 Zornitza Stark Publications for gene: HECW2 were set to
Genetic Epilepsy v0.881 HECW2 Zornitza Stark Mode of inheritance for gene: HECW2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.880 HECW2 Zornitza Stark reviewed gene: HECW2: Rating: GREEN; Mode of pathogenicity: Other; Publications: 29807643, 29395664, 27334371, 27389779; Phenotypes: Neurodevelopmental disorder with hypotonia, seizures, and absent language, MIM# 617268, intellectual disability, epilepsy, regression, microcephaly; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Angelman Rett like syndromes v0.19 HECW2 Zornitza Stark Phenotypes for gene: HECW2 were changed from intellectual disability; epilepsy; regression; microcephaly to Neurodevelopmental disorder with hypotonia, seizures, and absent language, MIM# 617268; intellectual disability; epilepsy; regression; microcephaly
Angelman Rett like syndromes v0.18 HECW2 Zornitza Stark Publications for gene: HECW2 were set to PMID: 29395664
Angelman Rett like syndromes v0.17 HECW2 Zornitza Stark Mode of pathogenicity for gene: HECW2 was changed from None to Other
Angelman Rett like syndromes v0.16 HECW2 Zornitza Stark reviewed gene: HECW2: Rating: GREEN; Mode of pathogenicity: Other; Publications: 29807643, 29395664, 27334371, 27389779; Phenotypes: Neurodevelopmental disorder with hypotonia, seizures, and absent language, MIM# 617268; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Angelman Rett like syndromes v0.16 HECW2 Zornitza Stark Classified gene: HECW2 as Green List (high evidence)
Angelman Rett like syndromes v0.16 HECW2 Zornitza Stark Gene: hecw2 has been classified as Green List (High Evidence).
Mendeliome v0.5046 HECW2 Zornitza Stark Marked gene: HECW2 as ready
Mendeliome v0.5046 HECW2 Zornitza Stark Gene: hecw2 has been classified as Green List (High Evidence).
Mendeliome v0.5046 HECW2 Zornitza Stark Publications for gene: HECW2 were set to
Mendeliome v0.5045 HECW2 Zornitza Stark Phenotypes for gene: HECW2 were changed from to Neurodevelopmental disorder with hypotonia, seizures, and absent language, MIM# 617268; intellectual disability; epilepsy; regression; microcephaly
Mendeliome v0.5044 HECW2 Zornitza Stark Mode of pathogenicity for gene: HECW2 was changed from to Other
Mendeliome v0.5043 HECW2 Zornitza Stark Mode of inheritance for gene: HECW2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Joubert syndrome and other neurological ciliopathies v0.88 Bryony Thompson Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Angelman Rett like syndromes v0.15 HECW2 Natasha Brown Marked gene: HECW2 as ready
Angelman Rett like syndromes v0.15 HECW2 Natasha Brown Gene: hecw2 has been classified as Red List (Low Evidence).
Angelman Rett like syndromes v0.15 HECW2 Natasha Brown gene: HECW2 was added
gene: HECW2 was added to Angelman Rett like syndromes. Sources: Literature
Mode of inheritance for gene: HECW2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HECW2 were set to PMID: 29395664
Phenotypes for gene: HECW2 were set to intellectual disability; epilepsy; regression; microcephaly
Penetrance for gene: HECW2 were set to Complete
Review for gene: HECW2 was set to GREEN
Added comment: Sources: Literature
Mendeliome v0.5042 HECW2 Natasha Brown reviewed gene: HECW2: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 29807643, 29395664, 27334371, 27389779; Phenotypes: intellectual disability, epilepsy, regression, microcephaly; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pituitary hormone deficiency v0.7 Zornitza Stark Panel types changed to Rare Disease
Dystonia and Chorea v0.152 C9orf72 Bryony Thompson Classified gene: C9orf72 as No list
Dystonia and Chorea v0.152 C9orf72 Bryony Thompson Gene: c9orf72 has been removed from the panel.
Dystonia and Chorea v0.151 C9orf72 Bryony Thompson Marked STR: C9orf72 as ready
Dystonia and Chorea v0.151 C9orf72 Bryony Thompson Str: c9orf72 has been classified as Green List (High Evidence).
Dystonia and Chorea v0.151 C9orf72 Bryony Thompson Classified STR: C9orf72 as Green List (high evidence)
Dystonia and Chorea v0.151 C9orf72 Bryony Thompson Str: c9orf72 has been classified as Green List (High Evidence).
Dystonia and Chorea v0.150 C9orf72 Bryony Thompson STR: C9orf72 was added
STR: C9orf72 was added to Dystonia - complex. Sources: Expert list
STR tags were added to STR: C9orf72.
Mode of inheritance for STR: C9orf72 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: C9orf72 were set to 26166205; 24363131; 26187722; 25577942
Phenotypes for STR: C9orf72 were set to Dystonia; Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 MIM#105550
Review for STR: C9orf72 was set to GREEN
STR: C9orf72 was marked as clinically relevant
Added comment: NG_031977​.1:g.5321GGGGCC[X]
Repeat expansion affects the protein degradation pathways and may contribute to TDP‐43 accumulation
Normal alleles: ≤25 G4C2 hexanucleotide repeat units generally considered normal
Pathogenic high-penetrance alleles: ≥60 G4C2 hexanucleotide repeat units are considered pathogenic
Note: The minimal size of a G4C2 pathogenic repeat is under debate: some studies consider repeats of >30 G4C2 hexanucleotide repeat units as pathogenic, whereas others use a cutoff of 60 G4C2 hexanucleotide repeat units.
Sources: Expert list
Mendeliome v0.5042 ARHGEF9 Zornitza Stark Mode of inheritance for gene: ARHGEF9 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.5041 ARHGEF9 Zornitza Stark edited their review of gene: ARHGEF9: Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Heterotaxy v1.0 Zornitza Stark promoted panel to version 1.0
Ciliary Dyskinesia v1.0 Zornitza Stark promoted panel to version 1.0
Mendeliome v0.5041 ZMYND10 Zornitza Stark Marked gene: ZMYND10 as ready
Mendeliome v0.5041 ZMYND10 Zornitza Stark Gene: zmynd10 has been classified as Green List (High Evidence).
Mendeliome v0.5041 ZMYND10 Zornitza Stark Phenotypes for gene: ZMYND10 were changed from to Ciliary dyskinesia, primary, 22, MIM#615444
Mendeliome v0.5040 ZMYND10 Zornitza Stark Publications for gene: ZMYND10 were set to
Mendeliome v0.5039 ZMYND10 Zornitza Stark Mode of inheritance for gene: ZMYND10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5038 ZMYND10 Zornitza Stark reviewed gene: ZMYND10: Rating: GREEN; Mode of pathogenicity: None; Publications: 23891471, 23891469; Phenotypes: Ciliary dyskinesia, primary, 22, MIM#615444; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.161 ZMYND10 Zornitza Stark reviewed gene: ZMYND10: Rating: GREEN; Mode of pathogenicity: None; Publications: 23891471, 23891469; Phenotypes: Ciliary dyskinesia, primary, 22, MIM#615444; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.161 HYDIN Zornitza Stark Marked gene: HYDIN as ready
Heterotaxy v0.161 HYDIN Zornitza Stark Gene: hydin has been classified as Red List (Low Evidence).
Heterotaxy v0.161 HYDIN Zornitza Stark Phenotypes for gene: HYDIN were changed from to Ciliary dyskinesia, primary, 5 (MIM#08647)
Mendeliome v0.5038 SPAG1 Zornitza Stark Marked gene: SPAG1 as ready
Mendeliome v0.5038 SPAG1 Zornitza Stark Gene: spag1 has been classified as Green List (High Evidence).
Mendeliome v0.5038 SPAG1 Zornitza Stark Phenotypes for gene: SPAG1 were changed from to Ciliary dyskinesia, primary, 28 (MIM#615505)
Mendeliome v0.5037 SPAG1 Zornitza Stark Publications for gene: SPAG1 were set to
Mendeliome v0.5036 SPAG1 Zornitza Stark Mode of inheritance for gene: SPAG1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5035 SPAG1 Zornitza Stark reviewed gene: SPAG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32622824, 32502479, 24055112; Phenotypes: Ciliary dyskinesia, primary, 28 (MIM#615505); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.160 SPAG1 Zornitza Stark changed review comment from: At least 5 unrelated families reported.; to: At least 15 unrelated families reported.
Heterotaxy v0.160 SPAG1 Zornitza Stark Marked gene: SPAG1 as ready
Heterotaxy v0.160 SPAG1 Zornitza Stark Gene: spag1 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.185 SPAG1 Zornitza Stark changed review comment from: At least 5 unrelated families reported.; to: At least 15 unrelated families reported.
Heterotaxy v0.160 SPAG1 Zornitza Stark Phenotypes for gene: SPAG1 were changed from to Ciliary dyskinesia, primary, 28 (MIM#615505)
Ciliary Dyskinesia v0.185 SPAG1 Zornitza Stark Publications for gene: SPAG1 were set to 24055112
Ciliary Dyskinesia v0.184 SPAG1 Zornitza Stark reviewed gene: SPAG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32622824, 32502479, 24055112; Phenotypes: Ciliary dyskinesia, primary, 28 (MIM#615505); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.159 SPAG1 Zornitza Stark Publications for gene: SPAG1 were set to
Heterotaxy v0.158 SPAG1 Zornitza Stark Mode of inheritance for gene: SPAG1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.157 SPAG1 Zornitza Stark reviewed gene: SPAG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24055112, 32622824, 32502479; Phenotypes: Ciliary dyskinesia, primary, 28 (MIM#615505); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.157 HYDIN Zornitza Stark Publications for gene: HYDIN were set to
Heterotaxy v0.156 HYDIN Zornitza Stark Mode of inheritance for gene: HYDIN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.155 HYDIN Zornitza Stark Classified gene: HYDIN as Red List (low evidence)
Heterotaxy v0.155 HYDIN Zornitza Stark Gene: hydin has been classified as Red List (Low Evidence).
Mendeliome v0.5035 MMP21 Zornitza Stark Marked gene: MMP21 as ready
Mendeliome v0.5035 MMP21 Zornitza Stark Gene: mmp21 has been classified as Green List (High Evidence).
Mendeliome v0.5035 MMP21 Zornitza Stark Phenotypes for gene: MMP21 were changed from to Heterotaxy, visceral, 7, autosomal,MIM# 616749
Mendeliome v0.5034 MMP21 Zornitza Stark Publications for gene: MMP21 were set to
Mendeliome v0.5033 MMP21 Zornitza Stark Mode of inheritance for gene: MMP21 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5032 MMP21 Zornitza Stark reviewed gene: MMP21: Rating: GREEN; Mode of pathogenicity: None; Publications: 26429889, 26437028, 26437029; Phenotypes: Heterotaxy, visceral, 7, autosomal,MIM# 616749; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.154 MMP21 Zornitza Stark Marked gene: MMP21 as ready
Heterotaxy v0.154 MMP21 Zornitza Stark Gene: mmp21 has been classified as Green List (High Evidence).
Heterotaxy v0.154 MMP21 Zornitza Stark Phenotypes for gene: MMP21 were changed from to Heterotaxy, visceral, 7, autosomal,MIM# 616749
Heterotaxy v0.153 MMP21 Zornitza Stark Publications for gene: MMP21 were set to
Heterotaxy v0.152 MMP21 Zornitza Stark Mode of inheritance for gene: MMP21 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.151 MMP21 Zornitza Stark reviewed gene: MMP21: Rating: GREEN; Mode of pathogenicity: None; Publications: 26429889, 26437028, 26437029; Phenotypes: Heterotaxy, visceral, 7, autosomal,MIM# 616749; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5032 DNAAF1 Zornitza Stark Marked gene: DNAAF1 as ready
Mendeliome v0.5032 DNAAF1 Zornitza Stark Gene: dnaaf1 has been classified as Green List (High Evidence).
Mendeliome v0.5032 DNAAF1 Zornitza Stark Phenotypes for gene: DNAAF1 were changed from to Ciliary dyskinesia, primary, 13, MIM# 613193
Mendeliome v0.5031 DNAAF1 Zornitza Stark Publications for gene: DNAAF1 were set to
Mendeliome v0.5030 DNAAF1 Zornitza Stark Mode of inheritance for gene: DNAAF1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5029 DNAAF1 Zornitza Stark reviewed gene: DNAAF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19944400, 19944405, 32502479, 29228333, 27261005; Phenotypes: Ciliary dyskinesia, primary, 13, MIM# 613193; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.151 DNAAF1 Zornitza Stark Marked gene: DNAAF1 as ready
Heterotaxy v0.151 DNAAF1 Zornitza Stark Gene: dnaaf1 has been classified as Green List (High Evidence).
Heterotaxy v0.151 DNAAF1 Zornitza Stark Phenotypes for gene: DNAAF1 were changed from to Ciliary dyskinesia, primary, 13, MIM# 613193
Heterotaxy v0.150 DNAAF1 Zornitza Stark Publications for gene: DNAAF1 were set to
Heterotaxy v0.149 DNAAF1 Zornitza Stark Mode of inheritance for gene: DNAAF1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.148 DNAAF1 Zornitza Stark reviewed gene: DNAAF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19944400, 19944405, 32502479, 29228333, 27261005; Phenotypes: Ciliary dyskinesia, primary, 13, MIM# 613193; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.184 HYDIN Zornitza Stark Marked gene: HYDIN as ready
Ciliary Dyskinesia v0.184 HYDIN Zornitza Stark Gene: hydin has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.184 HYDIN Zornitza Stark Phenotypes for gene: HYDIN were changed from to Ciliary dyskinesia, primary, 5 (MIM#608647)
Ciliary Dyskinesia v0.183 HYDIN Zornitza Stark Publications for gene: HYDIN were set to
Ciliary Dyskinesia v0.182 HYDIN Zornitza Stark Mode of inheritance for gene: HYDIN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.181 DNAI2 Zornitza Stark Marked gene: DNAI2 as ready
Ciliary Dyskinesia v0.181 DNAI2 Zornitza Stark Gene: dnai2 has been classified as Green List (High Evidence).
Heterotaxy v0.147 LRRC6 Zornitza Stark Marked gene: LRRC6 as ready
Heterotaxy v0.147 LRRC6 Zornitza Stark Gene: lrrc6 has been classified as Green List (High Evidence).
Heterotaxy v0.147 LRRC6 Zornitza Stark Phenotypes for gene: LRRC6 were changed from to Ciliary dyskinesia, primary, 19, MIM# 614935
Mendeliome v0.5029 LRRC6 Zornitza Stark Marked gene: LRRC6 as ready
Mendeliome v0.5029 LRRC6 Zornitza Stark Gene: lrrc6 has been classified as Green List (High Evidence).
Heterotaxy v0.146 LRRC6 Zornitza Stark Publications for gene: LRRC6 were set to
Mendeliome v0.5029 LRRC6 Zornitza Stark Phenotypes for gene: LRRC6 were changed from to Ciliary dyskinesia, primary, 19, MIM# 614935
Mendeliome v0.5028 LRRC6 Zornitza Stark Publications for gene: LRRC6 were set to
Heterotaxy v0.145 LRRC6 Zornitza Stark Mode of inheritance for gene: LRRC6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5027 LRRC6 Zornitza Stark Mode of inheritance for gene: LRRC6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5026 LRRC6 Zornitza Stark reviewed gene: LRRC6: Rating: GREEN; Mode of pathogenicity: None; Publications: 23122589, 23891469, 32622824, 29511670; Phenotypes: Ciliary dyskinesia, primary, 19, MIM# 614935; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.144 LRRC6 Zornitza Stark reviewed gene: LRRC6: Rating: GREEN; Mode of pathogenicity: None; Publications: 23122589, 23891469, 32622824, 29511670; Phenotypes: Ciliary dyskinesia, primary, 19, MIM# 614935; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.181 LRRC6 Zornitza Stark Marked gene: LRRC6 as ready
Ciliary Dyskinesia v0.181 LRRC6 Zornitza Stark Gene: lrrc6 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.181 LRRC6 Zornitza Stark Phenotypes for gene: LRRC6 were changed from to Ciliary dyskinesia, primary, 19, MIM# 614935
Ciliary Dyskinesia v0.180 LRRC6 Zornitza Stark Publications for gene: LRRC6 were set to
Ciliary Dyskinesia v0.179 LRRC6 Zornitza Stark Mode of inheritance for gene: LRRC6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.178 LRRC6 Zornitza Stark reviewed gene: LRRC6: Rating: GREEN; Mode of pathogenicity: None; Publications: 23122589, 23891469, 32622824, 29511670; Phenotypes: Ciliary dyskinesia, primary, 19, MIM# 614935; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5026 GAS8 Zornitza Stark Marked gene: GAS8 as ready
Mendeliome v0.5026 GAS8 Zornitza Stark Gene: gas8 has been classified as Green List (High Evidence).
Mendeliome v0.5026 GAS8 Zornitza Stark Phenotypes for gene: GAS8 were changed from to Ciliary dyskinesia, primary, 33, MIM#616726
Mendeliome v0.5025 GAS8 Zornitza Stark Publications for gene: GAS8 were set to
Mendeliome v0.5024 GAS8 Zornitza Stark Mode of inheritance for gene: GAS8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5023 GAS8 Zornitza Stark reviewed gene: GAS8: Rating: GREEN; Mode of pathogenicity: None; Publications: 26387594, 27120127; Phenotypes: Ciliary dyskinesia, primary, 33, mIM# 616726; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.144 DNAI2 Zornitza Stark Marked gene: DNAI2 as ready
Heterotaxy v0.144 DNAI2 Zornitza Stark Gene: dnai2 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.178 GAS8 Zornitza Stark Marked gene: GAS8 as ready
Ciliary Dyskinesia v0.178 GAS8 Zornitza Stark Gene: gas8 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.178 GAS8 Zornitza Stark Phenotypes for gene: GAS8 were changed from to Ciliary dyskinesia, primary, 33, mIM# 616726
Ciliary Dyskinesia v0.177 GAS8 Zornitza Stark Publications for gene: GAS8 were set to
Ciliary Dyskinesia v0.176 GAS8 Zornitza Stark Mode of inheritance for gene: GAS8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.175 GAS8 Zornitza Stark reviewed gene: GAS8: Rating: GREEN; Mode of pathogenicity: None; Publications: 26387594, 27120127; Phenotypes: Ciliary dyskinesia, primary, 33, mIM# 616726; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.144 DNAI2 Zornitza Stark Phenotypes for gene: DNAI2 were changed from to Ciliary dyskinesia, primary, 9, with or without situs inversus, MIM# 612444
Heterotaxy v0.143 DNAI2 Zornitza Stark Publications for gene: DNAI2 were set to
Mendeliome v0.5023 DNAI2 Zornitza Stark Marked gene: DNAI2 as ready
Mendeliome v0.5023 DNAI2 Zornitza Stark Gene: dnai2 has been classified as Green List (High Evidence).
Mendeliome v0.5023 DNAI2 Zornitza Stark Phenotypes for gene: DNAI2 were changed from to Ciliary dyskinesia, primary, 9, with or without situs inversus, MIM# 612444
Heterotaxy v0.142 DNAI2 Zornitza Stark Mode of inheritance for gene: DNAI2 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5022 DNAI2 Zornitza Stark Publications for gene: DNAI2 were set to
Heterotaxy v0.141 DNAI2 Zornitza Stark Mode of inheritance for gene: DNAI2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5021 DNAI2 Zornitza Stark Mode of inheritance for gene: DNAI2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.175 DNAI2 Zornitza Stark Phenotypes for gene: DNAI2 were changed from to Ciliary dyskinesia, primary, 9, with or without situs inversus, MIM# 612444
Mendeliome v0.5020 DNAI2 Zornitza Stark reviewed gene: DNAI2: Rating: GREEN; Mode of pathogenicity: None; Publications: 18950741, 23261302; Phenotypes: Ciliary dyskinesia, primary, 9, with or without situs inversus, MIM# 612444; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.140 DNAI2 Zornitza Stark reviewed gene: DNAI2: Rating: GREEN; Mode of pathogenicity: None; Publications: 18950741, 23261302; Phenotypes: Ciliary dyskinesia, primary, 9, with or without situs inversus, MIM# 612444; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.174 DNAI2 Zornitza Stark Publications for gene: DNAI2 were set to
Ciliary Dyskinesia v0.173 DNAI2 Zornitza Stark Mode of inheritance for gene: DNAI2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.172 DNAI2 Zornitza Stark changed review comment from: Three unrelated families reported.; to: Four unrelated families reported.
Ciliary Dyskinesia v0.172 DNAI2 Zornitza Stark reviewed gene: DNAI2: Rating: GREEN; Mode of pathogenicity: None; Publications: 18950741, 23261302; Phenotypes: Ciliary dyskinesia, primary, 9, with or without situs inversus, MIM# 612444; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5020 DNAI1 Zornitza Stark Marked gene: DNAI1 as ready
Mendeliome v0.5020 DNAI1 Zornitza Stark Gene: dnai1 has been classified as Green List (High Evidence).
Mendeliome v0.5020 DNAI1 Zornitza Stark Phenotypes for gene: DNAI1 were changed from to Ciliary dyskinesia, primary, 1, with or without situs inversus, MIM# 244400
Mendeliome v0.5019 DNAI1 Zornitza Stark Publications for gene: DNAI1 were set to
Mendeliome v0.5018 DNAI1 Zornitza Stark Mode of inheritance for gene: DNAI1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5017 DNAI1 Zornitza Stark reviewed gene: DNAI1: Rating: GREEN; Mode of pathogenicity: None; Publications: 10577904, 11231901, 32502479, 31765523, 30622330; Phenotypes: Ciliary dyskinesia, primary, 1, with or without situs inversus, MIM# 244400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.140 DNAI1 Zornitza Stark Marked gene: DNAI1 as ready
Heterotaxy v0.140 DNAI1 Zornitza Stark Gene: dnai1 has been classified as Green List (High Evidence).
Heterotaxy v0.140 DNAI1 Zornitza Stark Phenotypes for gene: DNAI1 were changed from to Ciliary dyskinesia, primary, 1, with or without situs inversus, MIM# 244400
Heterotaxy v0.139 DNAI1 Zornitza Stark Publications for gene: DNAI1 were set to
Heterotaxy v0.138 DNAI1 Zornitza Stark Mode of inheritance for gene: DNAI1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.137 DNAI1 Zornitza Stark reviewed gene: DNAI1: Rating: GREEN; Mode of pathogenicity: None; Publications: 10577904, 11231901, 32502479, 31765523, 30622330; Phenotypes: Ciliary dyskinesia, primary, 1, with or without situs inversus, MIM# 244400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.172 DNAI1 Zornitza Stark Marked gene: DNAI1 as ready
Ciliary Dyskinesia v0.172 DNAI1 Zornitza Stark Gene: dnai1 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.172 DNAI1 Zornitza Stark Phenotypes for gene: DNAI1 were changed from to Ciliary dyskinesia, primary, 1, with or without situs inversus, MIM# 244400
Ciliary Dyskinesia v0.171 DNAI1 Zornitza Stark Publications for gene: DNAI1 were set to
Ciliary Dyskinesia v0.170 DNAI1 Zornitza Stark Mode of inheritance for gene: DNAI1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.169 DNAI1 Zornitza Stark reviewed gene: DNAI1: Rating: GREEN; Mode of pathogenicity: None; Publications: 10577904, 11231901, 32502479, 31765523, 30622330; Phenotypes: Ciliary dyskinesia, primary, 1, with or without situs inversus, MIM# 244400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5017 DNAH11 Zornitza Stark Publications for gene: DNAH11 were set to
Mendeliome v0.5016 DNAH11 Zornitza Stark reviewed gene: DNAH11: Rating: GREEN; Mode of pathogenicity: None; Publications: 12142464, 18022865, 22102620, 32633470, 31879361, 31765523, 31040315; Phenotypes: Ciliary dyskinesia, primary, 7, with or without situs inversus, MIM#611884; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.137 DNAH11 Zornitza Stark Marked gene: DNAH11 as ready
Heterotaxy v0.137 DNAH11 Zornitza Stark Gene: dnah11 has been classified as Green List (High Evidence).
Heterotaxy v0.137 DNAH11 Zornitza Stark Phenotypes for gene: DNAH11 were changed from to Ciliary dyskinesia, primary, 7, with or without situs inversus, MIM#611884
Heterotaxy v0.136 DNAH11 Zornitza Stark Publications for gene: DNAH11 were set to
Ciliary Dyskinesia v0.169 DNAH11 Zornitza Stark Marked gene: DNAH11 as ready
Ciliary Dyskinesia v0.169 DNAH11 Zornitza Stark Gene: dnah11 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.169 DNAH11 Zornitza Stark Phenotypes for gene: DNAH11 were changed from to Ciliary dyskinesia, primary, 7, with or without situs inversus, MIM#611884
Heterotaxy v0.135 DNAH11 Zornitza Stark Mode of inheritance for gene: DNAH11 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.134 DNAH11 Zornitza Stark reviewed gene: DNAH11: Rating: GREEN; Mode of pathogenicity: None; Publications: 12142464, 18022865, 22102620, 32633470, 31879361, 31765523, 31040315; Phenotypes: Ciliary dyskinesia, primary, 7, with or without situs inversus, MIM#611884; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.168 DNAH11 Zornitza Stark Publications for gene: DNAH11 were set to
Ciliary Dyskinesia v0.167 DNAH11 Zornitza Stark Mode of inheritance for gene: DNAH11 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.166 DNAH11 Zornitza Stark reviewed gene: DNAH11: Rating: GREEN; Mode of pathogenicity: None; Publications: 12142464, 18022865, 22102620, 32633470, 31879361, 31765523, 31040315; Phenotypes: Ciliary dyskinesia, primary, 7, with or without situs inversus, MIM#611884; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5016 DNAAF5 Zornitza Stark Marked gene: DNAAF5 as ready
Mendeliome v0.5016 DNAAF5 Zornitza Stark Gene: dnaaf5 has been classified as Green List (High Evidence).
Mendeliome v0.5016 DNAAF5 Zornitza Stark Phenotypes for gene: DNAAF5 were changed from to Ciliary dyskinesia, primary, 18, MIM# 614874
Mendeliome v0.5015 DNAAF5 Zornitza Stark Publications for gene: DNAAF5 were set to
Mendeliome v0.5014 DNAAF5 Zornitza Stark Mode of inheritance for gene: DNAAF5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5013 DNAAF5 Zornitza Stark reviewed gene: DNAAF5: Rating: GREEN; Mode of pathogenicity: None; Publications: 23040496, 29363216, 25232951; Phenotypes: Ciliary dyskinesia, primary, 18, MIM# 614874; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.134 DNAAF5 Zornitza Stark Marked gene: DNAAF5 as ready
Heterotaxy v0.134 DNAAF5 Zornitza Stark Gene: dnaaf5 has been classified as Green List (High Evidence).
Heterotaxy v0.134 DNAAF5 Zornitza Stark Phenotypes for gene: DNAAF5 were changed from to Ciliary dyskinesia, primary, 18, MIM# 614874
Heterotaxy v0.133 DNAAF5 Zornitza Stark Publications for gene: DNAAF5 were set to
Heterotaxy v0.132 DNAAF5 Zornitza Stark Mode of inheritance for gene: DNAAF5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.131 DNAAF5 Zornitza Stark reviewed gene: DNAAF5: Rating: GREEN; Mode of pathogenicity: None; Publications: 23040496, 29363216, 25232951; Phenotypes: Ciliary dyskinesia, primary, 18, MIM# 614874; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.166 DNAAF5 Zornitza Stark Marked gene: DNAAF5 as ready
Ciliary Dyskinesia v0.166 DNAAF5 Zornitza Stark Gene: dnaaf5 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.166 DNAAF5 Zornitza Stark Phenotypes for gene: DNAAF5 were changed from to Ciliary dyskinesia, primary, 18, MIM# 614874
Ciliary Dyskinesia v0.165 DNAAF5 Zornitza Stark Publications for gene: DNAAF5 were set to
Ciliary Dyskinesia v0.164 DNAAF5 Zornitza Stark Mode of inheritance for gene: DNAAF5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.163 DNAAF5 Zornitza Stark reviewed gene: DNAAF5: Rating: GREEN; Mode of pathogenicity: None; Publications: 23040496, 29363216, 25232951; Phenotypes: Ciliary dyskinesia, primary, 18, MIM# 614874; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5013 DNAAF3 Zornitza Stark Marked gene: DNAAF3 as ready
Mendeliome v0.5013 DNAAF3 Zornitza Stark Gene: dnaaf3 has been classified as Green List (High Evidence).
Mendeliome v0.5013 DNAAF3 Zornitza Stark Phenotypes for gene: DNAAF3 were changed from to Ciliary dyskinesia, primary, 2, MIM# 606763
Mendeliome v0.5012 DNAAF3 Zornitza Stark Publications for gene: DNAAF3 were set to
Mendeliome v0.5011 DNAAF3 Zornitza Stark Mode of inheritance for gene: DNAAF3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5010 DNAAF3 Zornitza Stark reviewed gene: DNAAF3: Rating: GREEN; Mode of pathogenicity: None; Publications: 22387996, 32622824, 31186518; Phenotypes: Ciliary dyskinesia, primary, 2, MIM# 606763; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.131 DNAAF3 Zornitza Stark Marked gene: DNAAF3 as ready
Heterotaxy v0.131 DNAAF3 Zornitza Stark Gene: dnaaf3 has been classified as Green List (High Evidence).
Heterotaxy v0.131 DNAAF3 Zornitza Stark Phenotypes for gene: DNAAF3 were changed from to Ciliary dyskinesia, primary, 2, MIM# 606763
Heterotaxy v0.130 DNAAF3 Zornitza Stark Publications for gene: DNAAF3 were set to
Heterotaxy v0.129 DNAAF3 Zornitza Stark Mode of inheritance for gene: DNAAF3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.128 DNAAF3 Zornitza Stark reviewed gene: DNAAF3: Rating: GREEN; Mode of pathogenicity: None; Publications: 22387996, 32622824, 31186518; Phenotypes: Ciliary dyskinesia, primary, 2, MIM# 606763; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.163 DNAAF3 Zornitza Stark Marked gene: DNAAF3 as ready
Ciliary Dyskinesia v0.163 DNAAF3 Zornitza Stark Gene: dnaaf3 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.163 DNAAF3 Zornitza Stark Phenotypes for gene: DNAAF3 were changed from to Ciliary dyskinesia, primary, 2, MIM# 606763
Ciliary Dyskinesia v0.162 DNAAF3 Zornitza Stark Publications for gene: DNAAF3 were set to
Ciliary Dyskinesia v0.161 DNAAF3 Zornitza Stark Mode of inheritance for gene: DNAAF3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.160 DNAAF3 Zornitza Stark reviewed gene: DNAAF3: Rating: GREEN; Mode of pathogenicity: None; Publications: 22387996, 32622824, 31186518; Phenotypes: Ciliary dyskinesia, primary, 2, MIM# 606763; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Disorders of immune dysregulation v0.67 RAB27A Zornitza Stark Marked gene: RAB27A as ready
Disorders of immune dysregulation v0.67 RAB27A Zornitza Stark Gene: rab27a has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.67 RAB27A Zornitza Stark Phenotypes for gene: RAB27A were changed from to Griscelli syndrome, type 2, MIM# 607624
Disorders of immune dysregulation v0.66 RAB27A Zornitza Stark Publications for gene: RAB27A were set to
Disorders of immune dysregulation v0.65 RAB27A Zornitza Stark Mode of inheritance for gene: RAB27A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Disorders of immune dysregulation v0.64 RAB27A Zornitza Stark reviewed gene: RAB27A: Rating: GREEN; Mode of pathogenicity: None; Publications: 10835631, 10704277, 19030707, 15163896, 12058346, 10859366; Phenotypes: Griscelli syndrome, type 2, MIM# 607624; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5010 RAB27A Zornitza Stark Marked gene: RAB27A as ready
Mendeliome v0.5010 RAB27A Zornitza Stark Gene: rab27a has been classified as Green List (High Evidence).
Mendeliome v0.5010 RAB27A Zornitza Stark Phenotypes for gene: RAB27A were changed from to Griscelli syndrome, type 2, MIM# 607624
Mendeliome v0.5009 RAB27A Zornitza Stark Publications for gene: RAB27A were set to
Mendeliome v0.5008 RAB27A Zornitza Stark Mode of inheritance for gene: RAB27A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5007 RAB27A Zornitza Stark reviewed gene: RAB27A: Rating: GREEN; Mode of pathogenicity: None; Publications: 10835631, 10704277, 19030707, 15163896, 12058346, 10859366; Phenotypes: Griscelli syndrome, type 2, MIM# 607624; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5007 DNAAF2 Zornitza Stark Marked gene: DNAAF2 as ready
Mendeliome v0.5007 DNAAF2 Zornitza Stark Gene: dnaaf2 has been classified as Green List (High Evidence).
Mendeliome v0.5007 DNAAF2 Zornitza Stark Phenotypes for gene: DNAAF2 were changed from to Ciliary dyskinesia, primary, 10, MIM# 612518
Mendeliome v0.5006 DNAAF2 Zornitza Stark Publications for gene: DNAAF2 were set to
Mendeliome v0.5005 DNAAF2 Zornitza Stark Mode of inheritance for gene: DNAAF2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5004 DNAAF2 Zornitza Stark reviewed gene: DNAAF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 19052621, 32638265, 31107948; Phenotypes: Ciliary dyskinesia, primary, 10, MIM# 612518; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.160 DNAAF2 Zornitza Stark Marked gene: DNAAF2 as ready
Ciliary Dyskinesia v0.160 DNAAF2 Zornitza Stark Gene: dnaaf2 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.160 DNAAF2 Zornitza Stark Phenotypes for gene: DNAAF2 were changed from to Ciliary dyskinesia, primary, 10, MIM# 612518
Ciliary Dyskinesia v0.159 DNAAF2 Zornitza Stark Publications for gene: DNAAF2 were set to
Ciliary Dyskinesia v0.158 DNAAF2 Zornitza Stark Mode of inheritance for gene: DNAAF2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.157 DNAAF2 Zornitza Stark reviewed gene: DNAAF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 19052621, 32638265, 31107948; Phenotypes: Ciliary dyskinesia, primary, 10, MIM# 612518; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5004 PPP1R13L Zornitza Stark Marked gene: PPP1R13L as ready
Mendeliome v0.5004 PPP1R13L Zornitza Stark Gene: ppp1r13l has been classified as Green List (High Evidence).
Mendeliome v0.5004 PPP1R13L Zornitza Stark Classified gene: PPP1R13L as Green List (high evidence)
Mendeliome v0.5004 PPP1R13L Zornitza Stark Gene: ppp1r13l has been classified as Green List (High Evidence).
Mendeliome v0.5003 PPP1R13L Zornitza Stark gene: PPP1R13L was added
gene: PPP1R13L was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: PPP1R13L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPP1R13L were set to 32666529; 28864777
Phenotypes for gene: PPP1R13L were set to Dilated cardiomyopathy, onset in infancy
Review for gene: PPP1R13L was set to GREEN
Added comment: Four families reported in PMID 28864777, but same homozygous variant, identity by descent. Five unrelated families reported in PMID 32666529. Severe progressive DCM with onset in infancy.
Sources: Expert list
Cardiomyopathy_Paediatric v0.26 PPP1R13L Zornitza Stark Marked gene: PPP1R13L as ready
Cardiomyopathy_Paediatric v0.26 PPP1R13L Zornitza Stark Gene: ppp1r13l has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.26 PPP1R13L Zornitza Stark Phenotypes for gene: PPP1R13L were changed from cardio-cutaneous syndrome; sudden cardiac death to Dilated cardiomyopathy, onset in infancy
Cardiomyopathy_Paediatric v0.25 PPP1R13L Zornitza Stark Publications for gene: PPP1R13L were set to 25691752; 19016676; 28069640; 15661756; 28864777
Cardiomyopathy_Paediatric v0.24 PPP1R13L Zornitza Stark reviewed gene: PPP1R13L: Rating: GREEN; Mode of pathogenicity: None; Publications: 32666529, 28864777; Phenotypes: Dilated cardiomyopathy, onset in infancy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v0.24 PDLIM3 Zornitza Stark Marked gene: PDLIM3 as ready
Cardiomyopathy_Paediatric v0.24 PDLIM3 Zornitza Stark Gene: pdlim3 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v0.24 PDLIM3 Zornitza Stark Phenotypes for gene: PDLIM3 were changed from to Hypertrophic cardiomyopathy
Cardiomyopathy_Paediatric v0.23 PDLIM3 Zornitza Stark Publications for gene: PDLIM3 were set to 25163546
Cardiomyopathy_Paediatric v0.22 PDLIM3 Zornitza Stark Classified gene: PDLIM3 as Red List (low evidence)
Cardiomyopathy_Paediatric v0.22 PDLIM3 Zornitza Stark Gene: pdlim3 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v0.21 PDLIM3 Zornitza Stark reviewed gene: PDLIM3: Rating: RED; Mode of pathogenicity: None; Publications: 30681346, 26455666, 20801532; Phenotypes: Hypertrophic cardiomyopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ciliary Dyskinesia v0.157 DNAAF1 Zornitza Stark Marked gene: DNAAF1 as ready
Ciliary Dyskinesia v0.157 DNAAF1 Zornitza Stark Gene: dnaaf1 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.157 DNAAF1 Zornitza Stark Phenotypes for gene: DNAAF1 were changed from to Ciliary dyskinesia, primary, 13, MIM# 613193
Ciliary Dyskinesia v0.156 DNAAF1 Zornitza Stark Publications for gene: DNAAF1 were set to
Ciliary Dyskinesia v0.155 DNAAF1 Zornitza Stark Mode of inheritance for gene: DNAAF1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.154 DNAAF1 Zornitza Stark reviewed gene: DNAAF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19944400, 19944405, 32502479, 29228333, 27261005; Phenotypes: Ciliary dyskinesia, primary, 13, MIM# 613193; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5002 CCNO Zornitza Stark Marked gene: CCNO as ready
Mendeliome v0.5002 CCNO Zornitza Stark Gene: ccno has been classified as Green List (High Evidence).
Mendeliome v0.5002 CCNO Zornitza Stark Phenotypes for gene: CCNO were changed from to Ciliary dyskinesia, primary, 29, MIM# 615872
Mendeliome v0.5001 CCNO Zornitza Stark Publications for gene: CCNO were set to
Mendeliome v0.5000 CCNO Zornitza Stark Mode of inheritance for gene: CCNO was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4999 CCNO Zornitza Stark reviewed gene: CCNO: Rating: GREEN; Mode of pathogenicity: None; Publications: 24747639, 31765523, 28801648; Phenotypes: Ciliary dyskinesia, primary, 29, MIM# 615872; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.154 CCNO Zornitza Stark Marked gene: CCNO as ready
Ciliary Dyskinesia v0.154 CCNO Zornitza Stark Gene: ccno has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.154 CCNO Zornitza Stark Phenotypes for gene: CCNO were changed from to Ciliary dyskinesia, primary, 29, MIM# 615872
Ciliary Dyskinesia v0.153 CCNO Zornitza Stark Publications for gene: CCNO were set to
Ciliary Dyskinesia v0.152 CCNO Zornitza Stark Mode of inheritance for gene: CCNO was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.151 CCNO Zornitza Stark reviewed gene: CCNO: Rating: GREEN; Mode of pathogenicity: None; Publications: 24747639, 31765523, 28801648; Phenotypes: Ciliary dyskinesia, primary, 29, MIM# 615872; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4999 CSNK1G1 Zornitza Stark Marked gene: CSNK1G1 as ready
Mendeliome v0.4999 CSNK1G1 Zornitza Stark Gene: csnk1g1 has been classified as Green List (High Evidence).
Mendeliome v0.4999 CSNK1G1 Zornitza Stark Classified gene: CSNK1G1 as Green List (high evidence)
Mendeliome v0.4999 CSNK1G1 Zornitza Stark Gene: csnk1g1 has been classified as Green List (High Evidence).
Mendeliome v0.4998 CSNK1G1 Zornitza Stark gene: CSNK1G1 was added
gene: CSNK1G1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CSNK1G1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CSNK1G1 were set to 33009664
Phenotypes for gene: CSNK1G1 were set to Global developmental delay; Intellectual disability; Autism; Seizures
Review for gene: CSNK1G1 was set to GREEN
Added comment: Borderline Green/Amber rating.

Gold et al (2020 - PMID: 33009664) report 5 individuals with CSNK1G1 variants, including updated information on a previously reported subject (Martin et al 2014 - PMID: 24463883).

Features included DD (5/5) with associated expressive language delay, ASD (in at least 3/5), seizures (2/5), dysmorphic facial features (4/5 arched eyebrows, 3/5 prominent central incisors, 2/5 epicanthus) and limb anomalies (2/5 - proximally placed thumb, 5th f. clinodactyly, asymmetric overgrowth - the other individual had tapering fingers). GI problems were observed in 4/5. Two individuals had macrocephaly and one had microcephaly. There was no formal developmental assessment although ID might be implied in at least 3 individuals (p1: 20y - single words/regression in walking following a seizure episode, p2: 8y - first words at 5y, assistance to feed, dress and bathe, ASD, p4: 13y - regression, assistance to feed and dress).

CSNK1G1 encodes the gamma-1 isoform of casein kinase 1, a protein involved in growth and cell morphogenesis. The gene has ubiquitous expression, incl. brain. As commented, in brain it regulates phosphorylation of NMDA receptors, playing a role in synaptic transmission (4 articles cited).

One individual had a 1.2 kb deletion spanning exon 3 of CSNK1G1 [chr15:64550952-64552120 - GRCh37]. Parental samples were unavailable for this individual. Four individuals were found to harbor de novo CSNK1G1 variants [NM_022048.3: c.688C>T - p.(Arg230Trp) dn | c.1255C>T - p.(Gln419*) dn | c.1214+5G>A dn with in silico predictions in favor of splice disruption | c.419C>T - p.(Thr140Met) dn].

Arg230Trp is however present once in gnomAD. The stopgain variant is located in the last exon and predicted to skip NMD.

There were no variant studies performed.

The Drosophila gish gene encodes a CK1γ homolog with preferential expression in the mushroom body. Heterozygous and homozygous mutants exhibit impairment in memory retention, more severe in homozygous flies. gish was also identified as a seizure modifier in a fly epilepsy model (heterozygous para mt flies).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3081 CSNK1G1 Zornitza Stark Marked gene: CSNK1G1 as ready
Intellectual disability syndromic and non-syndromic v0.3081 CSNK1G1 Zornitza Stark Added comment: Comment when marking as ready: Borderline Green/Amber rating.
Intellectual disability syndromic and non-syndromic v0.3081 CSNK1G1 Zornitza Stark Gene: csnk1g1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3081 CSNK1G1 Zornitza Stark Classified gene: CSNK1G1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3081 CSNK1G1 Zornitza Stark Gene: csnk1g1 has been classified as Green List (High Evidence).
Mendeliome v0.4997 LMNB2 Zornitza Stark Marked gene: LMNB2 as ready
Mendeliome v0.4997 LMNB2 Zornitza Stark Gene: lmnb2 has been classified as Green List (High Evidence).
Mendeliome v0.4997 LMNB2 Zornitza Stark Phenotypes for gene: LMNB2 were changed from to {Lipodystrophy, partial, acquired, susceptibility to} 608709; Congenital microcephaly, Intellectual disability
Mendeliome v0.4996 LMNB2 Zornitza Stark Publications for gene: LMNB2 were set to
Mendeliome v0.4995 LMNB2 Zornitza Stark Mode of inheritance for gene: LMNB2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4994 LMNB2 Zornitza Stark reviewed gene: LMNB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 16826530, 22768673, 33033404; Phenotypes: {Lipodystrophy, partial, acquired, susceptibility to} 608709, Congenital microcephaly, Intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Lipodystrophy_Lipoatrophy v0.10 LMNB2 Zornitza Stark Marked gene: LMNB2 as ready
Lipodystrophy_Lipoatrophy v0.10 LMNB2 Zornitza Stark Gene: lmnb2 has been classified as Amber List (Moderate Evidence).
Lipodystrophy_Lipoatrophy v0.10 LMNB2 Zornitza Stark Phenotypes for gene: LMNB2 were changed from to {Lipodystrophy, partial, acquired, susceptibility to} 608709
Lipodystrophy_Lipoatrophy v0.9 LMNB2 Zornitza Stark Publications for gene: LMNB2 were set to
Lipodystrophy_Lipoatrophy v0.8 LMNB2 Zornitza Stark Mode of inheritance for gene: LMNB2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Lipodystrophy_Lipoatrophy v0.7 LMNB2 Zornitza Stark Classified gene: LMNB2 as Amber List (moderate evidence)
Lipodystrophy_Lipoatrophy v0.7 LMNB2 Zornitza Stark Gene: lmnb2 has been classified as Amber List (Moderate Evidence).
Lipodystrophy_Lipoatrophy v0.6 LMNB2 Zornitza Stark reviewed gene: LMNB2: Rating: AMBER; Mode of pathogenicity: None; Publications: 16826530, 22768673; Phenotypes: {Lipodystrophy, partial, acquired, susceptibility to} 608709; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3080 LMNB2 Zornitza Stark Marked gene: LMNB2 as ready
Intellectual disability syndromic and non-syndromic v0.3080 LMNB2 Zornitza Stark Gene: lmnb2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3080 LMNB2 Zornitza Stark Classified gene: LMNB2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3080 LMNB2 Zornitza Stark Gene: lmnb2 has been classified as Green List (High Evidence).
Microcephaly v0.491 LMNB2 Zornitza Stark Marked gene: LMNB2 as ready
Microcephaly v0.491 LMNB2 Zornitza Stark Gene: lmnb2 has been classified as Green List (High Evidence).
Microcephaly v0.491 LMNB2 Zornitza Stark Classified gene: LMNB2 as Green List (high evidence)
Microcephaly v0.491 LMNB2 Zornitza Stark Gene: lmnb2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3079 LMNB1 Zornitza Stark changed review comment from: Adult-onset neurodegenerative condition, not truly ID.; to: Adult-onset neurodegenerative condition, not truly ID. Associated with CNV of this gene, suggestive of haploinsufficiency.
Intellectual disability syndromic and non-syndromic v0.3079 LMNB1 Zornitza Stark Publications for gene: LMNB1 were set to 32910914
Mendeliome v0.4994 LMNB1 Zornitza Stark Publications for gene: LMNB1 were set to 32910914; 16951681; 19151023
Mendeliome v0.4993 LMNB1 Zornitza Stark edited their review of gene: LMNB1: Added comment: Additional study PMID 33033404 reporting 7 individuals with recurrent missense variants in this gene and ID/microcephaly phenotype.; Changed publications: 32910914, 16951681, 19151023, 33033404
Intellectual disability syndromic and non-syndromic v0.3078 CSNK1G1 Konstantinos Varvagiannis changed review comment from: Gold et al (2020 - PMID: 33009664) report 5 individuals with CSNK1G1 variants, including updated information on a previously reported subject (Martin et al 2014 - PMID: 24463883).

Features included DD (5/5) with associated expressive language delay, ASD (in at least 3/5), seizures (2/5), dysmorphic facial features (4/5 arched eyebrows, 3/5 prominent central incisors, 2/5 epicanthus) and limb anomalies (2/5 - proximally placed thumb, 5th f. clinodactyly, asymmetric overgrowth - the other individual had tapering fingers). GI problems were observed in 4/5. Two individuals had macrocephaly and one had microcephaly. There was no formal developmental assessment although ID might be implied in at least 3 individuals (p1: 20y - single words/regression in walking following a seizure episode, p2: 8y - first words at 5y, assistance to feed, dress and bathe, ASD, p4: 13y - regression, assistance to feed and dress).

CSNK1G1 encodes the gamma-1 isoform of casein kinase 1, a protein involved in growth and cell morphogenesis. The gene has ubiquitous expression, incl. brain. As commented, in brain it regulates phosphorylation of NMDA receptors, playing a role in synaptic transmission (4 articles cited).

One individual had a 1.2 kb deletion spanning exon 3 of CSNK1G1 [chr15:64550952-64552120 - GRCh37]. Parental samples were unavailable for this individual. Four individuals were found to harbor de novo CSNK1G1 variants [NM_022048.3: c.688C>T - p.(Arg230Trp) dn | c.1255C>T - p.(Gln419*) dn | c.1214+5G>A dn with in silico predictions in favor of splice disruption | c.419C>T - p.(Thr140Met) dn].

Arg230Trp is however present once in gnomAD. The stopgain variant is located in the last exon and predicted to skip NMD.

There were no variant studies performed.

The Drosophila gish gene encodes a CK1γ homolog with preferential expression in the mushroom body. Heterozygous and homozygous mutants exhibit impairment in memory retention, more severe in homozygous flies. gish was also identified as a seizure modifier in a fly epilepsy model (heterozygous para mt flies).

The authors also speculate that impaired transduction of LRP6 (and WNT signaling) might be implicated.

Finally the authors discuss the phenotype of individuals in Decipher one of whom (327861) harbors a frameshift variant and presenting ID, epilepsy and progressive spasticity. [NB. Inheritance of this variant is not specified, while this individual has a further inherited SCN2A missense SNV]. Two further Decipher cases with microdeletions spanning CSNK1G1 (and additional variants) are also discussed.

Overall, this gene can be considered for inclusion with probably amber rating.
Sources: Literature; to: Gold et al (2020 - PMID: 33009664) report 5 individuals with CSNK1G1 variants, including updated information on a previously reported subject (Martin et al 2014 - PMID: 24463883).

Features included DD (5/5) with associated expressive language delay, ASD (in at least 3/5), seizures (2/5), dysmorphic facial features (4/5 arched eyebrows, 3/5 prominent central incisors, 2/5 epicanthus) and limb anomalies (2/5 - proximally placed thumb, 5th f. clinodactyly, asymmetric overgrowth - the other individual had tapering fingers). GI problems were observed in 4/5. Two individuals had macrocephaly and one had microcephaly. There was no formal developmental assessment although ID might be implied in at least 3 individuals (p1: 20y - single words/regression in walking following a seizure episode, p2: 8y - first words at 5y, assistance to feed, dress and bathe, ASD, p4: 13y - regression, assistance to feed and dress).

CSNK1G1 encodes the gamma-1 isoform of casein kinase 1, a protein involved in growth and cell morphogenesis. The gene has ubiquitous expression, incl. brain. As commented, in brain it regulates phosphorylation of NMDA receptors, playing a role in synaptic transmission (4 articles cited).

One individual had a 1.2 kb deletion spanning exon 3 of CSNK1G1 [chr15:64550952-64552120 - GRCh37]. Parental samples were unavailable for this individual. Four individuals were found to harbor de novo CSNK1G1 variants [NM_022048.3: c.688C>T - p.(Arg230Trp) dn | c.1255C>T - p.(Gln419*) dn | c.1214+5G>A dn with in silico predictions in favor of splice disruption | c.419C>T - p.(Thr140Met) dn].

Arg230Trp is however present once in gnomAD. The stopgain variant is located in the last exon and predicted to skip NMD.

There were no variant studies performed.

The Drosophila gish gene encodes a CK1γ homolog with preferential expression in the mushroom body. Heterozygous and homozygous mutants exhibit impairment in memory retention, more severe in homozygous flies. gish was also identified as a seizure modifier in a fly epilepsy model (heterozygous para mt flies).

The authors also speculate that impaired transduction of LRP6 (and WNT signaling) might be implicated.

Finally the authors discuss the phenotype of individuals in Decipher one of whom (327861) harbors a frameshift variant and presented ID, epilepsy and progressive spasticity. [NB. Inheritance of this variant is not specified, while this individual has a further inherited SCN2A missense SNV]. Two further Decipher cases with microdeletions spanning CSNK1G1 (and additional variants) are also discussed.

Overall, this gene can be considered for inclusion with probably amber rating.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3078 CSNK1G1 Konstantinos Varvagiannis changed review comment from: Gold et al (2020 - PMID: 33009664) report 5 individuals with CSNK1G1 variants, including updated information on a previously reported subject (Martin et al 2014 - PMID: 24463883).

Features included DD (5/5) with associated expressive language delay, ASD (in at least 3/5), seizures (2/5), dysmorphic facial features (4/5 arched eyebrows, 3/5 prominent central incisors, 2/5 epicanthus) and limb anomalies (2/5 - proximally placed thumb, 5th f. clinodactyly, asymmetric overgrowth - the other individual had tapering fingers). GI problems were observed in 4/5. Two individuals had macrocephaly and one had microcephaly. There was no formal developmental assessment although ID might be implied in at least 3 individuals (p1: 20y - single words/regression in walking following a seizure episode, p2: 8y - first words at 5y, assistance to feed, dress and bathe, ASD, p4: 13y - regression, assistance to feed and dress).

CSNK1G1 encodes the gamma-1 isoform of casein kinase 1, a protein involved in growth and cell morphogenesis. The gene has ubiquitous expression, incl. brain. As commented, in brain it regulates phosphorylation of NMDA receptors, playing a role in synaptic transmission (4 articles cited).

One individual had a 1.2 kb deletion spanning exon 3 of CSNK1G1 [chr15:64550952-64552120 - GRCh37]. Parental samples were unavailable for this individual. Four individuals were found to harbor de novo CSNK1G1 variants [NM_022048.3: c.688C>T - p.(Arg230Trp) dn | c.1255C>T - p.(Gln419*) dn | c.1214+5G>A dn with in silico predictions in favor of splice disruption | c.419C>T - p.(Thr140Met) dn].

Arg230Trp is however present once in gnomAD. The stopgain variant is located in the last exon and predicted to skip NMD.

There were no variant studies performed.

The Drosophila gish gene encodes a CK1γ homolog with preferential expression in the mushroom body. Heterozygous and homozygous mutants exhibit impairment in memory retention, more severe in homozygous flies. gish was also identified as a seizure modifier in a fly epilepsy model (heterozygous para mt flies).

The authors also speculate that impaired transduction of LRP6 (and WNT signaling) might be implicated.

Finally the authors discuss the phenotype of individuals in Decipher one of whom (327861) harbors a frameshift variant and presenting ID, epilepsy and progressive spasticity. [NB. Inheritance of this variant is not specified, while this individual has a further inherited SCN2A missense SNV]. Two further Decipher cases with microdeletions spanning CSNK1G1 (and additional variants) also discussed.

Overall, this gene can be considered for inclusion with probably amber rating.
Sources: Literature; to: Gold et al (2020 - PMID: 33009664) report 5 individuals with CSNK1G1 variants, including updated information on a previously reported subject (Martin et al 2014 - PMID: 24463883).

Features included DD (5/5) with associated expressive language delay, ASD (in at least 3/5), seizures (2/5), dysmorphic facial features (4/5 arched eyebrows, 3/5 prominent central incisors, 2/5 epicanthus) and limb anomalies (2/5 - proximally placed thumb, 5th f. clinodactyly, asymmetric overgrowth - the other individual had tapering fingers). GI problems were observed in 4/5. Two individuals had macrocephaly and one had microcephaly. There was no formal developmental assessment although ID might be implied in at least 3 individuals (p1: 20y - single words/regression in walking following a seizure episode, p2: 8y - first words at 5y, assistance to feed, dress and bathe, ASD, p4: 13y - regression, assistance to feed and dress).

CSNK1G1 encodes the gamma-1 isoform of casein kinase 1, a protein involved in growth and cell morphogenesis. The gene has ubiquitous expression, incl. brain. As commented, in brain it regulates phosphorylation of NMDA receptors, playing a role in synaptic transmission (4 articles cited).

One individual had a 1.2 kb deletion spanning exon 3 of CSNK1G1 [chr15:64550952-64552120 - GRCh37]. Parental samples were unavailable for this individual. Four individuals were found to harbor de novo CSNK1G1 variants [NM_022048.3: c.688C>T - p.(Arg230Trp) dn | c.1255C>T - p.(Gln419*) dn | c.1214+5G>A dn with in silico predictions in favor of splice disruption | c.419C>T - p.(Thr140Met) dn].

Arg230Trp is however present once in gnomAD. The stopgain variant is located in the last exon and predicted to skip NMD.

There were no variant studies performed.

The Drosophila gish gene encodes a CK1γ homolog with preferential expression in the mushroom body. Heterozygous and homozygous mutants exhibit impairment in memory retention, more severe in homozygous flies. gish was also identified as a seizure modifier in a fly epilepsy model (heterozygous para mt flies).

The authors also speculate that impaired transduction of LRP6 (and WNT signaling) might be implicated.

Finally the authors discuss the phenotype of individuals in Decipher one of whom (327861) harbors a frameshift variant and presenting ID, epilepsy and progressive spasticity. [NB. Inheritance of this variant is not specified, while this individual has a further inherited SCN2A missense SNV]. Two further Decipher cases with microdeletions spanning CSNK1G1 (and additional variants) are also discussed.

Overall, this gene can be considered for inclusion with probably amber rating.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3078 CSNK1G1 Konstantinos Varvagiannis gene: CSNK1G1 was added
gene: CSNK1G1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CSNK1G1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CSNK1G1 were set to 33009664
Phenotypes for gene: CSNK1G1 were set to Global developmental delay; Intellectual disability; Autism; Seizures; Abnormality of the face; Abnromality of limbs
Penetrance for gene: CSNK1G1 were set to unknown
Review for gene: CSNK1G1 was set to AMBER
Added comment: Gold et al (2020 - PMID: 33009664) report 5 individuals with CSNK1G1 variants, including updated information on a previously reported subject (Martin et al 2014 - PMID: 24463883).

Features included DD (5/5) with associated expressive language delay, ASD (in at least 3/5), seizures (2/5), dysmorphic facial features (4/5 arched eyebrows, 3/5 prominent central incisors, 2/5 epicanthus) and limb anomalies (2/5 - proximally placed thumb, 5th f. clinodactyly, asymmetric overgrowth - the other individual had tapering fingers). GI problems were observed in 4/5. Two individuals had macrocephaly and one had microcephaly. There was no formal developmental assessment although ID might be implied in at least 3 individuals (p1: 20y - single words/regression in walking following a seizure episode, p2: 8y - first words at 5y, assistance to feed, dress and bathe, ASD, p4: 13y - regression, assistance to feed and dress).

CSNK1G1 encodes the gamma-1 isoform of casein kinase 1, a protein involved in growth and cell morphogenesis. The gene has ubiquitous expression, incl. brain. As commented, in brain it regulates phosphorylation of NMDA receptors, playing a role in synaptic transmission (4 articles cited).

One individual had a 1.2 kb deletion spanning exon 3 of CSNK1G1 [chr15:64550952-64552120 - GRCh37]. Parental samples were unavailable for this individual. Four individuals were found to harbor de novo CSNK1G1 variants [NM_022048.3: c.688C>T - p.(Arg230Trp) dn | c.1255C>T - p.(Gln419*) dn | c.1214+5G>A dn with in silico predictions in favor of splice disruption | c.419C>T - p.(Thr140Met) dn].

Arg230Trp is however present once in gnomAD. The stopgain variant is located in the last exon and predicted to skip NMD.

There were no variant studies performed.

The Drosophila gish gene encodes a CK1γ homolog with preferential expression in the mushroom body. Heterozygous and homozygous mutants exhibit impairment in memory retention, more severe in homozygous flies. gish was also identified as a seizure modifier in a fly epilepsy model (heterozygous para mt flies).

The authors also speculate that impaired transduction of LRP6 (and WNT signaling) might be implicated.

Finally the authors discuss the phenotype of individuals in Decipher one of whom (327861) harbors a frameshift variant and presenting ID, epilepsy and progressive spasticity. [NB. Inheritance of this variant is not specified, while this individual has a further inherited SCN2A missense SNV]. Two further Decipher cases with microdeletions spanning CSNK1G1 (and additional variants) also discussed.

Overall, this gene can be considered for inclusion with probably amber rating.
Sources: Literature
Microcephaly v0.490 LMNB1 Zornitza Stark Publications for gene: LMNB1 were set to 32910914
Cataract v0.238 SREBF1 Zornitza Stark Marked gene: SREBF1 as ready
Cataract v0.238 SREBF1 Zornitza Stark Gene: srebf1 has been classified as Green List (High Evidence).
Cataract v0.238 SREBF1 Zornitza Stark Classified gene: SREBF1 as Green List (high evidence)
Cataract v0.238 SREBF1 Zornitza Stark Gene: srebf1 has been classified as Green List (High Evidence).
Cataract v0.237 SREBF1 Zornitza Stark gene: SREBF1 was added
gene: SREBF1 was added to Cataract. Sources: Expert Review
Mode of inheritance for gene: SREBF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SREBF1 were set to 31790666; 32902915
Phenotypes for gene: SREBF1 were set to Mucoepithelial dysplasia, hereditary, MIM#158310
Review for gene: SREBF1 was set to GREEN
Added comment: HMD phenotype: 5 unrelated families reported with heterozygous variants at same residue (p.Arg557Cys and p.Arg557His) and a panepithelial defect involving the oral, nasal, conjunctival, vaginal, cervical, perineal, urethral, and bladder mucosa. Individuals developed cataracts, blindness, nonscarring alopecia, perineal psoriasiform lesions, and follicular keratoses.
Sources: Expert Review
Hair disorders v0.38 SREBF1 Zornitza Stark Marked gene: SREBF1 as ready
Hair disorders v0.38 SREBF1 Zornitza Stark Gene: srebf1 has been classified as Green List (High Evidence).
Hair disorders v0.38 SREBF1 Zornitza Stark Classified gene: SREBF1 as Green List (high evidence)
Hair disorders v0.38 SREBF1 Zornitza Stark Gene: srebf1 has been classified as Green List (High Evidence).
Hair disorders v0.37 SREBF1 Zornitza Stark gene: SREBF1 was added
gene: SREBF1 was added to Hair disorders. Sources: Expert Review
Mode of inheritance for gene: SREBF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SREBF1 were set to 32497488; 31790666; 32902915
Phenotypes for gene: SREBF1 were set to IFAP (ichthyosis follicularis, atrichia, and photophobia) syndrome 2, MIM619016; Mucoepithelial dysplasia, hereditary, MIM#158310
Review for gene: SREBF1 was set to GREEN
Added comment: HMD phenotype: 5 unrelated families reported with heterozygous variants at same residue (p.Arg557Cys and p.Arg557His) and a panepithelial defect involving the oral, nasal, conjunctival, vaginal, cervical, perineal, urethral, and bladder mucosa. Individuals developed cataracts, blindness, nonscarring alopecia, perineal psoriasiform lesions, and follicular keratoses.

IFAP phenotype: 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: Expert Review
Mendeliome v0.4993 SREBF1 Zornitza Stark Phenotypes for gene: SREBF1 were changed from IFAP (ichthyosis follicularis, atrichia, and photophobia) syndrome 2, MIM619016 to IFAP (ichthyosis follicularis, atrichia, and photophobia) syndrome 2, MIM619016; Mucoepithelial dysplasia, hereditary, MIM#158310
Mendeliome v0.4992 SREBF1 Zornitza Stark Publications for gene: SREBF1 were set to 32497488
Mendeliome v0.4991 SREBF1 Zornitza Stark edited their review of gene: SREBF1: Added comment: HMD phenotype: 5 unrelated families reported with heterozygous variants at same residue (p.Arg557Cys and p.Arg557His) and a panepithelial defect involving the oral, nasal, conjunctival, vaginal, cervical, perineal, urethral, and bladder mucosa. Individuals developed cataracts, blindness, nonscarring alopecia, perineal psoriasiform lesions, and follicular keratoses.; Changed publications: 32497488, 31790666, 32902915; Changed phenotypes: IFAP (ichthyosis follicularis, atrichia, and photophobia) syndrome 2, MIM619016, Mucoepithelial dysplasia, hereditary, MIM#158310
Ichthyosis and Porokeratosis v0.100 SREBF1 Zornitza Stark Phenotypes for gene: SREBF1 were changed from IFAP (ichthyosis follicularis, atrichia, and photophobia) syndrome 2, MIM619016 to IFAP (ichthyosis follicularis, atrichia, and photophobia) syndrome 2, MIM619016; Mucoepithelial dysplasia, hereditary, MIM#158310
Ichthyosis and Porokeratosis v0.99 SREBF1 Zornitza Stark Publications for gene: SREBF1 were set to 32497488
Ichthyosis and Porokeratosis v0.98 SREBF1 Zornitza Stark changed review comment from: 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; to: IFAP phenotype: 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
Ichthyosis and Porokeratosis v0.98 SREBF1 Zornitza Stark edited their review of gene: SREBF1: Added comment: HMD phenotype: 5 unrelated families reported with heterozygous variants at same residue (p.Arg557Cys and p.Arg557His) and a panepithelial defect involving the oral, nasal, conjunctival, vaginal, cervical, perineal, urethral, and bladder mucosa. Individuals developed cataracts, blindness, nonscarring alopecia, perineal psoriasiform lesions, and follicular keratoses.; Changed publications: 32497488, 31790666, 32902915; Changed phenotypes: IFAP (ichthyosis follicularis, atrichia, and photophobia) syndrome 2, MIM619016, Mucoepithelial dysplasia, hereditary, MIM#158310
Microcephaly v0.489 LMNB2 Konstantinos Varvagiannis gene: LMNB2 was added
gene: LMNB2 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: LMNB2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: LMNB2 were set to 33033404
Phenotypes for gene: LMNB2 were set to Congenital microcephaly; Global developmental delay; Intellectual disability
Penetrance for gene: LMNB2 were set to Complete
Mode of pathogenicity for gene: LMNB2 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: LMNB2 was set to GREEN
Added comment: Parry et al (2020 - PMID: 33033404) in a study to identify novel microcephaly genes using the DDD and 100k genomes project (100kGP) patient cohort, report on the phenotype of 13 individuals with heterozygous variant in LMNB1 (N=7) and LMNB2 (N=6).

LMNB1 : The authors identified 3 recurrent variants (c.97A>G - p.Lys33Glu (3), c.97_99del - p.Lys33del (2) , c.269G>C - p.Arg90Pro (2) / NM_005573.4) in seven individuals (3 from the DDD study, 4 from the 100kGP). In all cases were segregation studies were possible, the variant had occurred as a de novo event.

LMNB2 : 4 individuals from the DDD cohort and 1 from the 100kGP were found to harbor the same missense SNV (NM_032737.4:c.1192G>A, p.Glu398Lys). The variant had occurred de novo in 3 subjects and was inherited from a mosaic - unaffected - parent in a further case. Another individual was found to harbor c.160A>C - p.Asn54His.

LMNB1/2 common phenotypes :
All cases had congenital microcephaly (OFC -5.85 +/- 1.14 SD) apart from one individual, without history of IUGR or postnatally abnormal height (the latter in most).

Neuroimaging suggested structurally normal brain without abnormal migration. Gyral simplification / global reduction in white matter / increased extra axial spaces / enlarged ventricles were reported in 2.

LMNB1 - Global developmental delay was a feature in all (mild to severe) with some having occasional words at 7y (P3), absent speech (P9 - age category 5-10y) or ID not further specified (P13).

LMNB2 - DD was a feature in all 6 subjects (5/6 moderate to severe - 1/6 GDD). 5/6 were 10y or older with language (in 3 language not achieved) and motor deficits (walking not achieved in 1/6 - occurred at the age of 6y in 1/6).

Facial features were not consistent nor suggestive of a syndromic diagnosis (sloping forehead in some).

Overall, as the authors comment, the phenotype corresponded to a severe nonsyndromic microcephaly (although additional features were reported in some).

Animal model:
Microcephaly is supported by Lmnb1 ko mouse model. Lmnb1/2 ko mice however display migration defects, while Lmnb2 ko mice do not have reduced size at birth. Heterozygous Lmnb1 mice do not present microcephaly. It is suggested that while animal models support a similar (to the human) phenotype the underlying mechanism is different.

Variant effect :
variants were shown to affect highly conserved residues within the lamin a-helical rod-domain. As affected residues are conserved in LMNA, modelling with available LMNA PDB structures, suggested disrupted interactions required for higher-order assembly of lamin filaments.

Recurrence of specific variants at specific residues, absence of pLoF ones, the htz mouse Lmnb1 phenotype (absence of microcephaly) and the proposed mechanism (perturbation of complex formation) suggest a gain-of-function/dominant-negative effect rather than happloinsufficiency.

[Please also note the additional OMIM phenotypes for LMNB1 / LMNB2 - not here reviewed]
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3078 LMNB2 Konstantinos Varvagiannis changed review comment from: Please consider inclusion of LMNB2 in the ID panel with amber/green rating.

Parry et al (2020 - PMID: 33033404) in a study to identify novel microcephaly genes using the DDD and 100k genomes project (100kGP) patient cohort, report on the phenotype of 13 individuals with heterozygous variant in LMNB1 (N=7) and LMNB2 (N=6).

LMNB1 : The authors identified 3 recurrent variants (c.97A>G - p.Lys33Glu (3), c.97_99del - p.Lys33del (2) , c.269G>C - p.Arg90Pro (2) / NM_005573.4) in seven individuals (3 from the DDD study, 4 from the 100kGP). In all cases were segregation studies were possible, the variant had occurred as a de novo event.

LMNB2 : 4 individuals from the DDD cohort and 1 from the 100kGP were found to harbor the same missense SNV (NM_032737.4:c.1192G>A, p.Glu398Lys). The variant had occurred de novo in 3 subjects and was inherited from a mosaic - unaffected - parent in a further case. Another individual was found to harbor c.160A>C - p.Asn54His.

LMNB1/2 common phenotypes :
All cases had congenital microcephaly (OFC -5.85 +/- 1.14 SD) appart from one individual, without history of IUGR or postnatally abnormal height (the latter in most).

Neuroimaging suggested structurally normal brain without abnormal migration. Gyral simplification / global reduction in white matter / increased extra axial spaces / enlarged ventricles were reported in 2.

LMNB1 - Global developmental delay was a feature in all (mild to severe) with some having occasional words at 7y (P3), absent speech (P9 - age category 5-10y) or ID not further specified (P13).

LMNB2 - DD was a feature in all 6 subjects (5/6 moderate to severe - 1/6 GDD). 5/6 were 10y or older with language (in 3 language not achieved) and motor deficits (walking not achieved in 1/6 - occured at the age of 6y in 1/6).

Facial features were not consistent nor suggestive of a syndromic diagnosis (sloping forehead in some).

Overall, as the authors comment, the phenotype corresponded to a severe nonsyndromic microcephaly (although additional features were reported in some).

Animal model:
Microcephaly is supported by Lmnb1 ko mouse model. Lmnb1/2 ko mice however display migration defects, while Lmnb2 ko mice do not have reduced size at birth. Heterozygous Lmnb1 mice do not present microcephaly. It is suggested that while animal models support a similar (to the human) phenotype the underlying mechanism is different.

Variant effect :
variants were shown to affect highly conserved residues within the lamin a-helical rod-domain. As affected residues are conserved in LMNA, modelling with available LMNA PDB structures, suggested disrupted interactions required for higher-order assembly of lamin filaments.

Recurrence of specific variants at specific residues, absence of pLoF ones, the htz mouse Lmnb1 phenotype (absence of microcephaly) and the proposed mechanism (perturbation of complex formation) suggest a gain-of-function/dominant-negative effect rather than happloinsufficiency.

[Please also note the additional OMIM phenotypes for LMNB1 / LMNB2 - not here reviewed]
Sources: Literature; to: Please consider inclusion of LMNB2 in the ID panel with amber/green rating.

Parry et al (2020 - PMID: 33033404) in a study to identify novel microcephaly genes using the DDD and 100k genomes project (100kGP) patient cohort, report on the phenotype of 13 individuals with heterozygous variant in LMNB1 (N=7) and LMNB2 (N=6).

LMNB1 : The authors identified 3 recurrent variants (c.97A>G - p.Lys33Glu (3), c.97_99del - p.Lys33del (2) , c.269G>C - p.Arg90Pro (2) / NM_005573.4) in seven individuals (3 from the DDD study, 4 from the 100kGP). In all cases were segregation studies were possible, the variant had occurred as a de novo event.

LMNB2 : 4 individuals from the DDD cohort and 1 from the 100kGP were found to harbor the same missense SNV (NM_032737.4:c.1192G>A, p.Glu398Lys). The variant had occurred de novo in 3 subjects and was inherited from a mosaic - unaffected - parent in a further case. Another individual was found to harbor c.160A>C - p.Asn54His.

LMNB1/2 common phenotypes :
All cases had congenital microcephaly (OFC -5.85 +/- 1.14 SD) apart from one individual, without history of IUGR or postnatally abnormal height (the latter in most).

Neuroimaging suggested structurally normal brain without abnormal migration. Gyral simplification / global reduction in white matter / increased extra axial spaces / enlarged ventricles were reported in 2.

LMNB1 - Global developmental delay was a feature in all (mild to severe) with some having occasional words at 7y (P3), absent speech (P9 - age category 5-10y) or ID not further specified (P13).

LMNB2 - DD was a feature in all 6 subjects (5/6 moderate to severe - 1/6 GDD). 5/6 were 10y or older with language (in 3 language not achieved) and motor deficits (walking not achieved in 1/6 - occurred at the age of 6y in 1/6).

Facial features were not consistent nor suggestive of a syndromic diagnosis (sloping forehead in some).

Overall, as the authors comment, the phenotype corresponded to a severe nonsyndromic microcephaly (although additional features were reported in some).

Animal model:
Microcephaly is supported by Lmnb1 ko mouse model. Lmnb1/2 ko mice however display migration defects, while Lmnb2 ko mice do not have reduced size at birth. Heterozygous Lmnb1 mice do not present microcephaly. It is suggested that while animal models support a similar (to the human) phenotype the underlying mechanism is different.

Variant effect :
variants were shown to affect highly conserved residues within the lamin a-helical rod-domain. As affected residues are conserved in LMNA, modelling with available LMNA PDB structures, suggested disrupted interactions required for higher-order assembly of lamin filaments.

Recurrence of specific variants at specific residues, absence of pLoF ones, the htz mouse Lmnb1 phenotype (absence of microcephaly) and the proposed mechanism (perturbation of complex formation) suggest a gain-of-function/dominant-negative effect rather than happloinsufficiency.

[Please also note the additional OMIM phenotypes for LMNB1 / LMNB2 - not here reviewed]
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3078 LMNB2 Konstantinos Varvagiannis gene: LMNB2 was added
gene: LMNB2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: LMNB2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: LMNB2 were set to 33033404
Phenotypes for gene: LMNB2 were set to Congenital microcephaly; Global developmental delay; Intellectual disability
Penetrance for gene: LMNB2 were set to Complete
Mode of pathogenicity for gene: LMNB2 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: LMNB2 was set to GREEN
Added comment: Please consider inclusion of LMNB2 in the ID panel with amber/green rating.

Parry et al (2020 - PMID: 33033404) in a study to identify novel microcephaly genes using the DDD and 100k genomes project (100kGP) patient cohort, report on the phenotype of 13 individuals with heterozygous variant in LMNB1 (N=7) and LMNB2 (N=6).

LMNB1 : The authors identified 3 recurrent variants (c.97A>G - p.Lys33Glu (3), c.97_99del - p.Lys33del (2) , c.269G>C - p.Arg90Pro (2) / NM_005573.4) in seven individuals (3 from the DDD study, 4 from the 100kGP). In all cases were segregation studies were possible, the variant had occurred as a de novo event.

LMNB2 : 4 individuals from the DDD cohort and 1 from the 100kGP were found to harbor the same missense SNV (NM_032737.4:c.1192G>A, p.Glu398Lys). The variant had occurred de novo in 3 subjects and was inherited from a mosaic - unaffected - parent in a further case. Another individual was found to harbor c.160A>C - p.Asn54His.

LMNB1/2 common phenotypes :
All cases had congenital microcephaly (OFC -5.85 +/- 1.14 SD) appart from one individual, without history of IUGR or postnatally abnormal height (the latter in most).

Neuroimaging suggested structurally normal brain without abnormal migration. Gyral simplification / global reduction in white matter / increased extra axial spaces / enlarged ventricles were reported in 2.

LMNB1 - Global developmental delay was a feature in all (mild to severe) with some having occasional words at 7y (P3), absent speech (P9 - age category 5-10y) or ID not further specified (P13).

LMNB2 - DD was a feature in all 6 subjects (5/6 moderate to severe - 1/6 GDD). 5/6 were 10y or older with language (in 3 language not achieved) and motor deficits (walking not achieved in 1/6 - occured at the age of 6y in 1/6).

Facial features were not consistent nor suggestive of a syndromic diagnosis (sloping forehead in some).

Overall, as the authors comment, the phenotype corresponded to a severe nonsyndromic microcephaly (although additional features were reported in some).

Animal model:
Microcephaly is supported by Lmnb1 ko mouse model. Lmnb1/2 ko mice however display migration defects, while Lmnb2 ko mice do not have reduced size at birth. Heterozygous Lmnb1 mice do not present microcephaly. It is suggested that while animal models support a similar (to the human) phenotype the underlying mechanism is different.

Variant effect :
variants were shown to affect highly conserved residues within the lamin a-helical rod-domain. As affected residues are conserved in LMNA, modelling with available LMNA PDB structures, suggested disrupted interactions required for higher-order assembly of lamin filaments.

Recurrence of specific variants at specific residues, absence of pLoF ones, the htz mouse Lmnb1 phenotype (absence of microcephaly) and the proposed mechanism (perturbation of complex formation) suggest a gain-of-function/dominant-negative effect rather than happloinsufficiency.

[Please also note the additional OMIM phenotypes for LMNB1 / LMNB2 - not here reviewed]
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3078 LMNB1 Konstantinos Varvagiannis commented on gene: LMNB1: There is an additional report on LMBN1/2-associated phenotypes supporting green rating of the gene in the current panel.

Parry et al (2020 - PMID: 33033404) in a study to identify novel microcephaly genes using the DDD and 100k genomes project (100kGP) patient cohort, report on the phenotype of 13 individuals with heterozygous variant in LMNB1 (N=7) and LMNB2 (N=6).

LMNB1 : The authors identified 3 recurrent variants (c.97A>G - p.Lys33Glu (3), c.97_99del - p.Lys33del (2) , c.269G>C - p.Arg90Pro (2) / NM_005573.4) in seven individuals (3 from the DDD study, 4 from the 100kGP). In all cases were segregation studies were possible, the variant had occurred as a de novo event.

LMNB2 : 4 individuals from the DDD cohort and 1 from the 100kGP were found to harbor the same missense SNV (NM_032737.4:c.1192G>A, p.Glu398Lys). The variant had occurred de novo in 3 subjects and was inherited from a mosaic - unaffected - parent in a further case. Another individual was found to harbor c.160A>C - p.Asn54His.

LMNB1/2 common phenotypes :
All cases had congenital microcephaly (OFC -5.85 +/- 1.14 SD) appart from one individual, without history of IUGR or postnatally abnormal height (the latter in most).

Neuroimaging suggested structurally normal brain without abnormal migration. Gyral simplification / global reduction in white matter / increased extra axial spaces / enlarged ventricles were reported in 2.

LMNB1 - Global developmental delay was a feature in all (mild to severe) with some having occasional words at 7y (P3), absent speech (P9 - age category 5-10y) or ID not further specified (P13).

LMNB2 - DD was a feature in all 6 subjects (5/6 moderate to severe - 1/6 GDD). 5/6 were 10y or older with language (in 3 language not achieved) and motor deficits (walking not achieved in 1/6 - occured at the age of 6y in 1/6).

Facial features were not consistent nor suggestive of a syndromic diagnosis (sloping forehead in some).

Overall, as the authors comment, the phenotype corresponded to a severe nonsyndromic microcephaly (although additional features were reported in some).

Animal model:
Microcephaly is supported by Lmnb1 ko mouse model. Lmnb1/2 ko mice however display migration defects, while Lmnb2 ko mice do not have reduced size at birth. Heterozygous Lmnb1 mice do not present microcephaly. It is suggested that while animal models support a similar (to the human) phenotype the underlying mechanism is different.

Variant effect :
variants were shown to affect highly conserved residues within the lamin a-helical rod-domain. As affected residues are conserved in LMNA, modelling with available LMNA PDB structures, suggested disrupted interactions required for higher-order assembly of lamin filaments.

Recurrence of specific variants at specific residues, absence of pLoF ones, the htz mouse Lmnb1 phenotype (absence of microcephaly) and the proposed mechanism (perturbation of complex formation) suggest a gain-of-function/dominant-negative effect rather than happloinsufficiency.

[Please also note the additional OMIM phenotypes for LMNB1 / LMNB2 - not here reviewed]

--------
Microcephaly v0.489 LMNB1 Konstantinos Varvagiannis reviewed gene: LMNB1: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 33033404; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.4991 CCDC40 Zornitza Stark Marked gene: CCDC40 as ready
Mendeliome v0.4991 CCDC40 Zornitza Stark Gene: ccdc40 has been classified as Green List (High Evidence).
Mendeliome v0.4991 CCDC40 Zornitza Stark Phenotypes for gene: CCDC40 were changed from to Ciliary dyskinesia, primary, 15, MIM#613808
Mendeliome v0.4990 CCDC40 Zornitza Stark Publications for gene: CCDC40 were set to
Mendeliome v0.4989 CCDC40 Zornitza Stark Mode of inheritance for gene: CCDC40 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4988 CCDC40 Zornitza Stark reviewed gene: CCDC40: Rating: GREEN; Mode of pathogenicity: None; Publications: 21131974, 23255504, 31879361, 31765523, 31650533; Phenotypes: Ciliary dyskinesia, primary, 15, MIM#613808; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.128 CCDC40 Zornitza Stark Marked gene: CCDC40 as ready
Heterotaxy v0.128 CCDC40 Zornitza Stark Gene: ccdc40 has been classified as Green List (High Evidence).
Heterotaxy v0.128 CCDC40 Zornitza Stark Phenotypes for gene: CCDC40 were changed from to Ciliary dyskinesia, primary, 15, MIM#613808
Heterotaxy v0.127 CCDC40 Zornitza Stark Publications for gene: CCDC40 were set to
Heterotaxy v0.126 CCDC40 Zornitza Stark Mode of inheritance for gene: CCDC40 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.125 CCDC40 Zornitza Stark reviewed gene: CCDC40: Rating: GREEN; Mode of pathogenicity: None; Publications: 21131974, 23255504, 31879361, 31765523, 31650533; Phenotypes: Ciliary dyskinesia, primary, 15, MIM#613808; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.151 CCDC40 Zornitza Stark Marked gene: CCDC40 as ready
Ciliary Dyskinesia v0.151 CCDC40 Zornitza Stark Gene: ccdc40 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.151 CCDC40 Zornitza Stark Phenotypes for gene: CCDC40 were changed from to Ciliary dyskinesia, primary, 15, MIM#613808
Ciliary Dyskinesia v0.150 CCDC40 Zornitza Stark Publications for gene: CCDC40 were set to
Ciliary Dyskinesia v0.149 CCDC40 Zornitza Stark Mode of inheritance for gene: CCDC40 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.148 CCDC40 Zornitza Stark reviewed gene: CCDC40: Rating: GREEN; Mode of pathogenicity: None; Publications: 21131974, 23255504, 31879361, 31765523, 31650533; Phenotypes: Ciliary dyskinesia, primary, 15, MIM#613808; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4988 CCDC39 Zornitza Stark Marked gene: CCDC39 as ready
Mendeliome v0.4988 CCDC39 Zornitza Stark Gene: ccdc39 has been classified as Green List (High Evidence).
Mendeliome v0.4988 CCDC39 Zornitza Stark Phenotypes for gene: CCDC39 were changed from to Ciliary dyskinesia, primary, 14, MIM# 613807
Mendeliome v0.4987 CCDC39 Zornitza Stark Publications for gene: CCDC39 were set to
Mendeliome v0.4986 CCDC39 Zornitza Stark Mode of inheritance for gene: CCDC39 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4985 CCDC39 Zornitza Stark reviewed gene: CCDC39: Rating: GREEN; Mode of pathogenicity: None; Publications: 21131972, 23255504; Phenotypes: Ciliary dyskinesia, primary, 14, MIM# 613807; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.125 CCDC39 Zornitza Stark Marked gene: CCDC39 as ready
Heterotaxy v0.125 CCDC39 Zornitza Stark Gene: ccdc39 has been classified as Green List (High Evidence).
Heterotaxy v0.125 CCDC39 Zornitza Stark Phenotypes for gene: CCDC39 were changed from to Ciliary dyskinesia, primary, 14, MIM# 613807
Heterotaxy v0.124 CCDC39 Zornitza Stark Publications for gene: CCDC39 were set to
Heterotaxy v0.123 CCDC39 Zornitza Stark Mode of inheritance for gene: CCDC39 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.122 CCDC39 Zornitza Stark reviewed gene: CCDC39: Rating: GREEN; Mode of pathogenicity: None; Publications: 21131972, 23255504; Phenotypes: Ciliary dyskinesia, primary, 14, MIM# 613807; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.148 CCDC39 Zornitza Stark Marked gene: CCDC39 as ready
Ciliary Dyskinesia v0.148 CCDC39 Zornitza Stark Gene: ccdc39 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.148 CCDC39 Zornitza Stark Phenotypes for gene: CCDC39 were changed from to Ciliary dyskinesia, primary, 14, MIM# 613807
Ciliary Dyskinesia v0.147 CCDC39 Zornitza Stark Publications for gene: CCDC39 were set to
Ciliary Dyskinesia v0.146 CCDC39 Zornitza Stark Mode of inheritance for gene: CCDC39 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.145 CCDC39 Zornitza Stark reviewed gene: CCDC39: Rating: GREEN; Mode of pathogenicity: None; Publications: 21131972, 23255504; Phenotypes: Ciliary dyskinesia, primary, 14, MIM# 613807; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4985 CCDC151 Zornitza Stark Marked gene: CCDC151 as ready
Mendeliome v0.4985 CCDC151 Zornitza Stark Gene: ccdc151 has been classified as Green List (High Evidence).
Mendeliome v0.4985 CCDC151 Zornitza Stark Phenotypes for gene: CCDC151 were changed from to Ciliary dyskinesia, primary, 30, MIM# 616037
Mendeliome v0.4984 CCDC151 Zornitza Stark Publications for gene: CCDC151 were set to
Mendeliome v0.4983 CCDC151 Zornitza Stark Mode of inheritance for gene: CCDC151 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4982 CCDC151 Zornitza Stark reviewed gene: CCDC151: Rating: GREEN; Mode of pathogenicity: None; Publications: 25192045, 25224326, 32490514, 32286033, 30504913; Phenotypes: Ciliary dyskinesia, primary, 30, MIM# 616037; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.122 CCDC151 Zornitza Stark Marked gene: CCDC151 as ready
Heterotaxy v0.122 CCDC151 Zornitza Stark Gene: ccdc151 has been classified as Green List (High Evidence).
Heterotaxy v0.122 CCDC151 Zornitza Stark Phenotypes for gene: CCDC151 were changed from to Ciliary dyskinesia, primary, 30, MIM# 616037
Heterotaxy v0.121 CCDC151 Zornitza Stark Publications for gene: CCDC151 were set to
Heterotaxy v0.120 CCDC151 Zornitza Stark Mode of inheritance for gene: CCDC151 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.145 CCDC151 Zornitza Stark Marked gene: CCDC151 as ready
Ciliary Dyskinesia v0.145 CCDC151 Zornitza Stark Gene: ccdc151 has been classified as Green List (High Evidence).
Heterotaxy v0.119 CCDC151 Zornitza Stark reviewed gene: CCDC151: Rating: GREEN; Mode of pathogenicity: None; Publications: 25192045, 25224326, 32490514, 32286033, 30504913; Phenotypes: Ciliary dyskinesia, primary, 30, MIM# 616037; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.145 CCDC151 Zornitza Stark Phenotypes for gene: CCDC151 were changed from to Ciliary dyskinesia, primary, 30, MIM# 616037
Ciliary Dyskinesia v0.144 CCDC151 Zornitza Stark Publications for gene: CCDC151 were set to
Ciliary Dyskinesia v0.143 CCDC151 Zornitza Stark Mode of inheritance for gene: CCDC151 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.142 CCDC151 Zornitza Stark reviewed gene: CCDC151: Rating: GREEN; Mode of pathogenicity: None; Publications: 25192045, 25224326, 32490514, 32286033, 30504913; Phenotypes: Ciliary dyskinesia, primary, 30, MIM# 616037; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4982 CCDC114 Zornitza Stark Marked gene: CCDC114 as ready
Mendeliome v0.4982 CCDC114 Zornitza Stark Gene: ccdc114 has been classified as Green List (High Evidence).
Mendeliome v0.4982 CCDC114 Zornitza Stark Phenotypes for gene: CCDC114 were changed from to Ciliary dyskinesia, primary, 20, MIM# 615067
Mendeliome v0.4981 CCDC114 Zornitza Stark Publications for gene: CCDC114 were set to
Mendeliome v0.4980 CCDC114 Zornitza Stark Mode of inheritance for gene: CCDC114 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4979 CCDC114 Zornitza Stark reviewed gene: CCDC114: Rating: GREEN; Mode of pathogenicity: None; Publications: 23261303, 23261302, 32855706, 23506398; Phenotypes: Ciliary dyskinesia, primary, 20, MIM# 615067; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.119 CCDC114 Zornitza Stark Marked gene: CCDC114 as ready
Heterotaxy v0.119 CCDC114 Zornitza Stark Gene: ccdc114 has been classified as Green List (High Evidence).
Heterotaxy v0.119 CCDC114 Zornitza Stark Phenotypes for gene: CCDC114 were changed from to Ciliary dyskinesia, primary, 20, MIM# 615067
Heterotaxy v0.118 CCDC114 Zornitza Stark Publications for gene: CCDC114 were set to
Heterotaxy v0.117 CCDC114 Zornitza Stark Mode of inheritance for gene: CCDC114 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.142 CCDC114 Zornitza Stark Marked gene: CCDC114 as ready
Ciliary Dyskinesia v0.142 CCDC114 Zornitza Stark Gene: ccdc114 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.142 CCDC114 Zornitza Stark Phenotypes for gene: CCDC114 were changed from Ciliary dyskinesia, primary, 20, MIM# 615067 to Ciliary dyskinesia, primary, 20, MIM# 615067
Ciliary Dyskinesia v0.141 CCDC114 Zornitza Stark Phenotypes for gene: CCDC114 were changed from to Ciliary dyskinesia, primary, 20, MIM# 615067
Heterotaxy v0.116 CCDC114 Zornitza Stark Mode of inheritance for gene: CCDC114 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.140 CCDC114 Zornitza Stark Publications for gene: CCDC114 were set to
Heterotaxy v0.115 CCDC114 Zornitza Stark reviewed gene: CCDC114: Rating: GREEN; Mode of pathogenicity: None; Publications: 23261303, 23261302, 32855706, 23506398; Phenotypes: Ciliary dyskinesia, primary, 20, MIM# 615067; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.139 CCDC114 Zornitza Stark Mode of inheritance for gene: CCDC114 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.138 CCDC114 Zornitza Stark reviewed gene: CCDC114: Rating: GREEN; Mode of pathogenicity: None; Publications: 23261303, 23261302, 32855706, 23506398; Phenotypes: Ciliary dyskinesia, primary, 20, MIM# 615067; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4979 CCDC103 Zornitza Stark Marked gene: CCDC103 as ready
Mendeliome v0.4979 CCDC103 Zornitza Stark Gene: ccdc103 has been classified as Green List (High Evidence).
Mendeliome v0.4979 CCDC103 Zornitza Stark Phenotypes for gene: CCDC103 were changed from to Ciliary dyskinesia, primary, 17, MIM# 614679
Mendeliome v0.4978 CCDC103 Zornitza Stark Publications for gene: CCDC103 were set to
Mendeliome v0.4977 CCDC103 Zornitza Stark Mode of inheritance for gene: CCDC103 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4976 CCDC103 Zornitza Stark Tag founder tag was added to gene: CCDC103.
Mendeliome v0.4976 CCDC103 Zornitza Stark reviewed gene: CCDC103: Rating: GREEN; Mode of pathogenicity: None; Publications: 22581229, 32447765, 31858719, 28790179; Phenotypes: Ciliary dyskinesia, primary, 17, MIM# 614679; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.115 CCDC103 Zornitza Stark Marked gene: CCDC103 as ready
Heterotaxy v0.115 CCDC103 Zornitza Stark Gene: ccdc103 has been classified as Green List (High Evidence).
Heterotaxy v0.115 CCDC103 Zornitza Stark Phenotypes for gene: CCDC103 were changed from to Ciliary dyskinesia, primary, 17, MIM# 614679
Heterotaxy v0.114 CCDC103 Zornitza Stark Publications for gene: CCDC103 were set to
Heterotaxy v0.113 CCDC103 Zornitza Stark Mode of inheritance for gene: CCDC103 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.112 CCDC103 Zornitza Stark Tag founder tag was added to gene: CCDC103.
Heterotaxy v0.112 CCDC103 Zornitza Stark reviewed gene: CCDC103: Rating: GREEN; Mode of pathogenicity: None; Publications: 22581229, 32447765, 31858719, 28790179; Phenotypes: Ciliary dyskinesia, primary, 17, MIM# 614679; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.137 CCDC103 Zornitza Stark Tag founder tag was added to gene: CCDC103.
Ciliary Dyskinesia v0.137 CCDC103 Zornitza Stark Marked gene: CCDC103 as ready
Ciliary Dyskinesia v0.137 CCDC103 Zornitza Stark Gene: ccdc103 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.137 CCDC103 Zornitza Stark Phenotypes for gene: CCDC103 were changed from to Ciliary dyskinesia, primary, 17, MIM# 614679
Ciliary Dyskinesia v0.136 CCDC103 Zornitza Stark Publications for gene: CCDC103 were set to
Ciliary Dyskinesia v0.135 CCDC103 Zornitza Stark Mode of inheritance for gene: CCDC103 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.134 CCDC103 Zornitza Stark reviewed gene: CCDC103: Rating: GREEN; Mode of pathogenicity: None; Publications: 22581229, 32447765, 31858719, 28790179; Phenotypes: Ciliary dyskinesia, primary, 17, MIM# 614679; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.516 AARS2 Zornitza Stark Marked gene: AARS2 as ready
Mitochondrial disease v0.516 AARS2 Zornitza Stark Gene: aars2 has been classified as Green List (High Evidence).
Mendeliome v0.4976 GARS Zornitza Stark Marked gene: GARS as ready
Mendeliome v0.4976 GARS Zornitza Stark Gene: gars has been classified as Green List (High Evidence).
Mendeliome v0.4976 GARS Zornitza Stark Phenotypes for gene: GARS were changed from to Spinal muscular atrophy, infantile, James type, MIM# 619042; Charcot-Marie-Tooth disease, type 2D, MIM# 601472; Neuronopathy, distal hereditary motor, type VA, MIM# 600794; Multi-system mitochondrial disorder
Mendeliome v0.4975 GARS Zornitza Stark Publications for gene: GARS were set to
Mendeliome v0.4974 GARS Zornitza Stark Mode of inheritance for gene: GARS was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4973 GARS Zornitza Stark Tag new gene name tag was added to gene: GARS.
Mendeliome v0.4973 GARS Zornitza Stark reviewed gene: GARS: Rating: GREEN; Mode of pathogenicity: None; Publications: 17101916, 22462675, 31985473, 32181591, 12690580, 25168514, 26503042, 29648643, 16982418, 24669931, 28594869; Phenotypes: Spinal muscular atrophy, infantile, James type, MIM# 619042, Charcot-Marie-Tooth disease, type 2D, MIM# 601472, Neuronopathy, distal hereditary motor, type VA, MIM# 600794, Multi-system mitochondrial disorder; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mitochondrial disease v0.516 GARS Zornitza Stark Marked gene: GARS as ready
Mitochondrial disease v0.516 GARS Zornitza Stark Added comment: Comment when marking as ready: New HGNC approved name is GARS1.
Mitochondrial disease v0.516 GARS Zornitza Stark Gene: gars has been classified as Green List (High Evidence).
Mitochondrial disease v0.516 GARS Zornitza Stark Tag new gene name tag was added to gene: GARS.
Mitochondrial disease v0.516 GARS Zornitza Stark Phenotypes for gene: GARS were changed from to Spinal muscular atrophy, infantile, James type, MIM# 619042; Charcot-Marie-Tooth disease, type 2D, MIM# 601472; Neuronopathy, distal hereditary motor, type VA, MIM# 600794; Multi-system mitochondrial disorder
Mitochondrial disease v0.515 GARS Zornitza Stark Publications for gene: GARS were set to
Mitochondrial disease v0.514 GARS Zornitza Stark Mode of inheritance for gene: GARS was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mitochondrial disease v0.513 GARS Zornitza Stark reviewed gene: GARS: Rating: GREEN; Mode of pathogenicity: None; Publications: 17101916, 22462675, 31985473, 32181591, 12690580, 25168514, 26503042, 29648643, 16982418, 24669931, 28594869; Phenotypes: Spinal muscular atrophy, infantile, James type, MIM# 619042, Charcot-Marie-Tooth disease, type 2D, MIM# 601472, Neuronopathy, distal hereditary motor, type VA, MIM# 600794, Multi-system mitochondrial disorder; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4973 SELENON Zornitza Stark Marked gene: SELENON as ready
Mendeliome v0.4973 SELENON Zornitza Stark Gene: selenon has been classified as Green List (High Evidence).
Mendeliome v0.4973 SELENON Zornitza Stark Phenotypes for gene: SELENON were changed from to Myopathy, congenital, with fiber-type disproportion, MIM# 255310; Muscular dystrophy, rigid spine, 1, MIM# 602771
Mendeliome v0.4972 SELENON Zornitza Stark Publications for gene: SELENON were set to
Mendeliome v0.4971 SELENON Zornitza Stark Mode of inheritance for gene: SELENON was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4970 SELENON Zornitza Stark reviewed gene: SELENON: Rating: GREEN; Mode of pathogenicity: None; Publications: 11528383, 12192640, 16365872, 21131290, 21131290, 32154989, 32796131; Phenotypes: Myopathy, congenital, with fiber-type disproportion, MIM# 255310, Muscular dystrophy, rigid spine, 1, MIM# 602771; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Arthrogryposis v0.238 TNNT1 Zornitza Stark Marked gene: TNNT1 as ready
Arthrogryposis v0.238 TNNT1 Zornitza Stark Gene: tnnt1 has been classified as Green List (High Evidence).
Arthrogryposis v0.238 TNNT1 Zornitza Stark Phenotypes for gene: TNNT1 were changed from to Nemaline myopathy 5, Amish type, MIM# 605355
Arthrogryposis v0.237 TNNT1 Zornitza Stark Publications for gene: TNNT1 were set to
Arthrogryposis v0.236 TNNT1 Zornitza Stark Mode of inheritance for gene: TNNT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.235 TNNT1 Zornitza Stark reviewed gene: TNNT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 10952871, 32994279, 32819427, 31970803, 31604653, 29931346, 31680123; Phenotypes: Nemaline myopathy 5, Amish type, MIM# 605355; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4970 TNNT1 Zornitza Stark Marked gene: TNNT1 as ready
Mendeliome v0.4970 TNNT1 Zornitza Stark Gene: tnnt1 has been classified as Green List (High Evidence).
Mendeliome v0.4970 TNNT1 Zornitza Stark Phenotypes for gene: TNNT1 were changed from to Nemaline myopathy 5, Amish type, MIM# 605355
Mendeliome v0.4969 TNNT1 Zornitza Stark Mode of inheritance for gene: TNNT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4968 TNNT1 Zornitza Stark reviewed gene: TNNT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 10952871, 32994279, 32819427, 31970803, 31604653, 29931346, 29178646; Phenotypes: Nemaline myopathy 5, Amish type, MIM# 605355; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.235 TNNT3 Zornitza Stark Marked gene: TNNT3 as ready
Arthrogryposis v0.235 TNNT3 Zornitza Stark Gene: tnnt3 has been classified as Green List (High Evidence).
Arthrogryposis v0.235 TNNT3 Zornitza Stark Phenotypes for gene: TNNT3 were changed from to Arthrogryposis, distal, type 2B2, MIM# 618435
Arthrogryposis v0.234 TNNT3 Zornitza Stark Publications for gene: TNNT3 were set to
Arthrogryposis v0.233 TNNT3 Zornitza Stark Mode of pathogenicity for gene: TNNT3 was changed from to Other
Arthrogryposis v0.232 TNNT3 Zornitza Stark Mode of inheritance for gene: TNNT3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Arthrogryposis v0.231 TNNT3 Zornitza Stark reviewed gene: TNNT3: Rating: GREEN; Mode of pathogenicity: Other; Publications: 12865991, 19142688, 21402185, 25337069, 17194691; Phenotypes: Arthrogryposis, distal, type 2B2, MIM# 618435; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4968 TNNT3 Zornitza Stark Marked gene: TNNT3 as ready
Mendeliome v0.4968 TNNT3 Zornitza Stark Gene: tnnt3 has been classified as Green List (High Evidence).
Mendeliome v0.4968 TNNT3 Zornitza Stark Phenotypes for gene: TNNT3 were changed from to Arthrogryposis, distal, type 2B2, MIM# 618435
Mendeliome v0.4967 TNNT3 Zornitza Stark Publications for gene: TNNT3 were set to
Mendeliome v0.4966 TNNT3 Zornitza Stark Mode of pathogenicity for gene: TNNT3 was changed from to Other
Mendeliome v0.4965 TNNT3 Zornitza Stark Mode of inheritance for gene: TNNT3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4964 TNNT3 Zornitza Stark reviewed gene: TNNT3: Rating: GREEN; Mode of pathogenicity: Other; Publications: 12865991, 19142688, 21402185, 25337069, 17194691; Phenotypes: Arthrogryposis, distal, type 2B2, MIM# 618435; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Additional findings_Paediatric v0.134 STAC3 Zornitza Stark Marked gene: STAC3 as ready
Additional findings_Paediatric v0.134 STAC3 Zornitza Stark Gene: stac3 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.134 STAC3 Zornitza Stark Phenotypes for gene: STAC3 were changed from Myopathy, Native American to Myopathy, congenital, Baily-Bloch, MIM# 255995
Additional findings_Paediatric v0.133 STAC3 Zornitza Stark Publications for gene: STAC3 were set to
Additional findings_Paediatric v0.132 STAC3 Zornitza Stark Classified gene: STAC3 as Green List (high evidence)
Additional findings_Paediatric v0.132 STAC3 Zornitza Stark Gene: stac3 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.131 STAC3 Zornitza Stark reviewed gene: STAC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 23736855, 28411587, 28777491, 30168660; Phenotypes: Myopathy, congenital, Baily-Bloch, MIM# 255995; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4964 STAC3 Zornitza Stark Marked gene: STAC3 as ready
Mendeliome v0.4964 STAC3 Zornitza Stark Gene: stac3 has been classified as Green List (High Evidence).
Mendeliome v0.4964 STAC3 Zornitza Stark Tag founder tag was added to gene: STAC3.
Mendeliome v0.4964 STAC3 Zornitza Stark Phenotypes for gene: STAC3 were changed from to Myopathy, congenital, Baily-Bloch, MIM# 255995
Mendeliome v0.4963 STAC3 Zornitza Stark Publications for gene: STAC3 were set to
Mendeliome v0.4962 STAC3 Zornitza Stark Mode of inheritance for gene: STAC3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4961 STAC3 Zornitza Stark reviewed gene: STAC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 23736855, 28411587, 28777491, 30168660; Phenotypes: Myopathy, congenital, Baily-Bloch, MIM# 255995; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mackenzie's Mission_Reproductive Carrier Screening v0.32 SPEG Zornitza Stark gene: SPEG was added
gene: SPEG was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Expert Review
Mode of inheritance for gene: SPEG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPEG were set to 25087613; 31625632; 30412272; 30157964; 29614691; 29474540; 28624463; 26578207; 25087613
Phenotypes for gene: SPEG were set to Centronuclear myopathy 5, MIM# 615959
Review for gene: SPEG was set to GREEN
Added comment: Centronuclear myopathy-5 is an autosomal recessive congenital myopathy characterized by severe neonatal hypotonia with respiratory insufficiency and difficulty feeding. Some individuals die in infancy, and some develop dilated cardiomyopathy. More than 10 unrelated families reported, functional data.
Sources: Expert Review
Additional findings_Paediatric v0.131 SPEG Zornitza Stark Marked gene: SPEG as ready
Additional findings_Paediatric v0.131 SPEG Zornitza Stark Gene: speg has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.131 SPEG Zornitza Stark Phenotypes for gene: SPEG were changed from Centronuclear myopathy with dilated cardiomyopathy to Centronuclear myopathy 5, MIM# 615959
Additional findings_Paediatric v0.130 SPEG Zornitza Stark Publications for gene: SPEG were set to
Additional findings_Paediatric v0.129 SPEG Zornitza Stark Classified gene: SPEG as Green List (high evidence)
Additional findings_Paediatric v0.129 SPEG Zornitza Stark Gene: speg has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.128 SPEG Zornitza Stark reviewed gene: SPEG: Rating: GREEN; Mode of pathogenicity: None; Publications: 25087613, 31625632, 30412272, 30157964, 29614691, 29474540, 28624463, 26578207, 25087613; Phenotypes: Centronuclear myopathy 5, MIM# 615959; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4961 SPEG Zornitza Stark Marked gene: SPEG as ready
Mendeliome v0.4961 SPEG Zornitza Stark Gene: speg has been classified as Green List (High Evidence).
Mendeliome v0.4961 SPEG Zornitza Stark Phenotypes for gene: SPEG were changed from to Centronuclear myopathy 5, MIM# 615959
Mendeliome v0.4960 SPEG Zornitza Stark Publications for gene: SPEG were set to
Mendeliome v0.4959 SPEG Zornitza Stark Mode of inheritance for gene: SPEG was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4958 SPEG Zornitza Stark reviewed gene: SPEG: Rating: GREEN; Mode of pathogenicity: None; Publications: 25087613, 31625632, 30412272, 30157964, 29614691, 29474540, 28624463, 26578207, 25087613; Phenotypes: Centronuclear myopathy 5, MIM# 615959; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4958 TPM3 Zornitza Stark Marked gene: TPM3 as ready
Mendeliome v0.4958 TPM3 Zornitza Stark Gene: tpm3 has been classified as Green List (High Evidence).
Mendeliome v0.4958 TPM3 Zornitza Stark Phenotypes for gene: TPM3 were changed from to CAP myopathy 1, MIM# 609284; Myopathy, congenital, with fiber-type disproportion, MIM# 255310; Nemaline myopathy 1, autosomal dominant or recessive, MIM# 609284; Congenital muscle stiffness
Mendeliome v0.4957 TPM3 Zornitza Stark Publications for gene: TPM3 were set to
Mendeliome v0.4956 TPM3 Zornitza Stark Mode of pathogenicity for gene: TPM3 was changed from to Other
Mendeliome v0.4955 TPM3 Zornitza Stark Mode of inheritance for gene: TPM3 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4954 TPM3 Zornitza Stark reviewed gene: TPM3: Rating: GREEN; Mode of pathogenicity: Other; Publications: 26418456, 7704029, 17376686, 18382475, 19487656; Phenotypes: CAP myopathy 1, MIM# 609284, Myopathy, congenital, with fiber-type disproportion, MIM# 255310, Nemaline myopathy 1, autosomal dominant or recessive, MIM# 609284, Congenital muscle stiffness; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mitochondrial disease v0.513 MICU1 Zornitza Stark Tag founder tag was added to gene: MICU1.
Mendeliome v0.4954 MICU1 Zornitza Stark Tag founder tag was added to gene: MICU1.
Muscular dystrophy and myopathy_Paediatric v0.76 MICU1 Zornitza Stark Marked gene: MICU1 as ready
Muscular dystrophy and myopathy_Paediatric v0.76 MICU1 Zornitza Stark Gene: micu1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.76 MICU1 Zornitza Stark Phenotypes for gene: MICU1 were changed from to Myopathy with extrapyramidal signs, MIM# 615673
Muscular dystrophy and myopathy_Paediatric v0.75 MICU1 Zornitza Stark Tag founder tag was added to gene: MICU1.
Muscular dystrophy and myopathy_Paediatric v0.75 MICU1 Zornitza Stark Publications for gene: MICU1 were set to
Muscular dystrophy and myopathy_Paediatric v0.74 MICU1 Zornitza Stark Mode of inheritance for gene: MICU1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.73 MICU1 Zornitza Stark reviewed gene: MICU1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24336167, 29721912, 32395406; Phenotypes: Myopathy with extrapyramidal signs, MIM# 615673; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3078 MICU1 Zornitza Stark Marked gene: MICU1 as ready
Intellectual disability syndromic and non-syndromic v0.3078 MICU1 Zornitza Stark Gene: micu1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3078 MICU1 Zornitza Stark Phenotypes for gene: MICU1 were changed from to Myopathy with extrapyramidal signs, MIM# 615673
Intellectual disability syndromic and non-syndromic v0.3077 MICU1 Zornitza Stark Publications for gene: MICU1 were set to
Intellectual disability syndromic and non-syndromic v0.3076 MICU1 Zornitza Stark Mode of inheritance for gene: MICU1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3075 MICU1 Zornitza Stark Tag founder tag was added to gene: MICU1.
Intellectual disability syndromic and non-syndromic v0.3075 MICU1 Zornitza Stark reviewed gene: MICU1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24336167, 29721912, 32395406; Phenotypes: Myopathy with extrapyramidal signs, MIM# 615673; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.513 MICU1 Zornitza Stark Marked gene: MICU1 as ready
Mitochondrial disease v0.513 MICU1 Zornitza Stark Gene: micu1 has been classified as Green List (High Evidence).
Mitochondrial disease v0.513 MICU1 Zornitza Stark Phenotypes for gene: MICU1 were changed from to Myopathy with extrapyramidal signs, MIM# 615673
Mitochondrial disease v0.512 MICU1 Zornitza Stark Publications for gene: MICU1 were set to
Mitochondrial disease v0.511 MICU1 Zornitza Stark Mode of inheritance for gene: MICU1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.510 MICU1 Zornitza Stark reviewed gene: MICU1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24336167, 29721912, 32395406; Phenotypes: Myopathy with extrapyramidal signs, MIM# 615673; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4954 MICU1 Zornitza Stark Marked gene: MICU1 as ready
Mendeliome v0.4954 MICU1 Zornitza Stark Gene: micu1 has been classified as Green List (High Evidence).
Mendeliome v0.4954 MICU1 Zornitza Stark Phenotypes for gene: MICU1 were changed from to Myopathy with extrapyramidal signs, MIM# 615673
Mendeliome v0.4953 MICU1 Zornitza Stark Publications for gene: MICU1 were set to
Mendeliome v0.4952 MICU1 Zornitza Stark Mode of inheritance for gene: MICU1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4951 MICU1 Zornitza Stark reviewed gene: MICU1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24336167, 29721912, 32395406; Phenotypes: Myopathy with extrapyramidal signs, MIM# 615673; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.231 LMOD3 Zornitza Stark Marked gene: LMOD3 as ready
Arthrogryposis v0.231 LMOD3 Zornitza Stark Gene: lmod3 has been classified as Green List (High Evidence).
Arthrogryposis v0.231 LMOD3 Zornitza Stark Phenotypes for gene: LMOD3 were changed from to Nemaline myopathy 10, MIM# 616165
Arthrogryposis v0.230 LMOD3 Zornitza Stark Publications for gene: LMOD3 were set to
Arthrogryposis v0.229 LMOD3 Zornitza Stark Mode of inheritance for gene: LMOD3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.228 LMOD3 Zornitza Stark reviewed gene: LMOD3: Rating: GREEN; Mode of pathogenicity: None; Publications: 29331079, 25250574, 30291184, 28815944, 30642739; Phenotypes: Nemaline myopathy 10, MIM# 616165; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4951 LMOD3 Zornitza Stark Marked gene: LMOD3 as ready
Mendeliome v0.4951 LMOD3 Zornitza Stark Gene: lmod3 has been classified as Green List (High Evidence).
Mendeliome v0.4951 LMOD3 Zornitza Stark Phenotypes for gene: LMOD3 were changed from to Nemaline myopathy 10, MIM# 616165
Mendeliome v0.4950 LMOD3 Zornitza Stark Publications for gene: LMOD3 were set to
Mendeliome v0.4949 LMOD3 Zornitza Stark Mode of inheritance for gene: LMOD3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4948 LMOD3 Zornitza Stark reviewed gene: LMOD3: Rating: GREEN; Mode of pathogenicity: None; Publications: 25250574, 30291184, 28815944, 30642739; Phenotypes: Nemaline myopathy 10, MIM# 616165; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3075 PIBF1 Zornitza Stark Phenotypes for gene: PIBF1 were changed from Joubert syndrome 33; OMIM #617767 to Joubert syndrome 33, OMIM #617767
Intellectual disability syndromic and non-syndromic v0.3074 PIBF1 Zornitza Stark Publications for gene: PIBF1 were set to PubMed: 26167768; 30858804; 29695797
Intellectual disability syndromic and non-syndromic v0.3073 PIBF1 Zornitza Stark reviewed gene: PIBF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33004012; Phenotypes: Joubert syndrome 33, OMIM #617767; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Joubert syndrome and other neurological ciliopathies v0.87 PIBF1 Zornitza Stark Publications for gene: PIBF1 were set to 26167768; 30858804; 29695797
Joubert syndrome and other neurological ciliopathies v0.86 PIBF1 Zornitza Stark edited their review of gene: PIBF1: Added comment: Another family reported.; Changed publications: 26167768, 30858804, 29695797, 33004012
Ciliopathies v0.213 PIBF1 Zornitza Stark Publications for gene: PIBF1 were set to PMID:26167768; 30858804; 29695797
Ciliopathies v0.212 PIBF1 Zornitza Stark reviewed gene: PIBF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33004012; Phenotypes: Joubert syndrome 33, OMIM #617767; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4948 PIBF1 Zornitza Stark Publications for gene: PIBF1 were set to 26167768; 30858804; 29695797
Mackenzie's Mission_Reproductive Carrier Screening v0.31 ACADM Sarah Righetti changed review comment from: MUTATIONAL AND CLINICAL SPECTRUM: Most common variant is NM_000016.6:c.985A>G p.K329E (p.K304E in mature protein) seen hom/chet in patients with classical MCAD deficiency, also seen chet in asymptomatic siblings. Beware existence of pseudodeficiency alleles (e.g. chet c.199T>C p.Y67H) where individuals have reduced enzymatic activity and so are positive on NBS but do not usually have clinical symptoms.

TREATMENT: Covered on NBS, generally very successful treatment with mainly dietary management. However 3 neonates in past year at WCH who have had cardiac/respiratory arrests before 48 hours (i.e. prior to NBS results being available). There are a number of babies who have died or had brain damage as a result of hypoglycemia prior to the test being taken.

Summary: GREEN; meets MM panel inclusion criteria where early diagnosis can lead to more effective treatment. Counsel accordingly.
Sources: Expert Review; to: Mutational and clinical spectrum: Most common variant is NM_000016.6:c.985A>G p.K329E (p.K304E in mature protein) seen hom/chet in patients with classical MCAD deficiency, also seen chet in asymptomatic siblings. Beware existence of pseudodeficiency alleles (e.g. chet c.199T>C p.Y67H) where individuals have reduced enzymatic activity and so are positive on NBS but do not usually have clinical symptoms.

Treatment: Covered on NBS, generally very successful treatment with mainly dietary management. However 3 neonates in past year at WCH who have had cardiac/respiratory arrests before 48 hours (i.e. prior to NBS results being available). There are a number of babies who have died or had brain damage as a result of hypoglycemia prior to the test being taken.

Summary: GREEN; meets MM panel inclusion criteria where early diagnosis can lead to more effective treatment. Counsel accordingly.
Sources: Expert Review
Mackenzie's Mission_Reproductive Carrier Screening v0.31 KCNE1 Seb Lunke changed review comment from: Comment by Ivan Macciocca:
as reported in Circulation. 2020 Feb 11;141(6):418-428 PMID: 31983240, by the International, Multicentered LQTS ClinGen Working Group:
Genetic evidence associating this gene with disease causality was also based on a candidate gene approach and was limited in scope. There is strong evidence for a role of KCNE1 in acquired LQTS which led the panel to classify it as having limited evidence for disease causality for unprovoked LQTS, although studies in large families with variant
segregation is lacking. Furthermore, several case reports have identified homozygous or compound heterozygous rare variants in KCNE1 in patients with Jervell and Lange-Nielsen syndrome; however, parents or siblings carrying only 1 allele have reported normal phenotypes, suggesting an association of this gene with an autosomal-recessive form of LQTS.

Comment by Zornitza Stark:
Rated as MODERATE by ClinGen for bi-allelic disease. Evidence for mono-allelic disease is limited.

Additional: Technically challenging as only coding exon has reduced mappability and putative (but disputed) pseudogene KCNE1B that was introduced in GRCh38, but is not present in GRCh37/hg19 (PMID31527855, PMID30936463); to: Comment by Ivan Macciocca:
as reported in Circulation. 2020 Feb 11;141(6):418-428 PMID: 31983240, by the International, Multicentered LQTS ClinGen Working Group:
Genetic evidence associating this gene with disease causality was also based on a candidate gene approach and was limited in scope. There is strong evidence for a role of KCNE1 in acquired LQTS which led the panel to classify it as having limited evidence for disease causality for unprovoked LQTS, although studies in large families with variant
segregation is lacking. Furthermore, several case reports have identified homozygous or compound heterozygous rare variants in KCNE1 in patients with Jervell and Lange-Nielsen syndrome; however, parents or siblings carrying only 1 allele have reported normal phenotypes, suggesting an association of this gene with an autosomal-recessive form of LQTS.

Comment by Zornitza Stark:
Rated as MODERATE by ClinGen for bi-allelic disease. Evidence for mono-allelic disease is limited.

Additional: Technically challenging as only coding exon has reduced mappability and putative (but disputed) pseudogene KCNE1B that was introduced in GRCh38, but is not present in GRCh37/hg19 (PMID31527855, PMID30936463)

Association with Long-QT is questionable. Remains GREEN for Deafness, but on balance does not currently meet inclusion criteria for Mackenzie's Mission
Mackenzie's Mission_Reproductive Carrier Screening v0.31 KCNE1 Seb Lunke Classified gene: KCNE1 as Amber List (moderate evidence)
Mackenzie's Mission_Reproductive Carrier Screening v0.31 KCNE1 Seb Lunke Gene: kcne1 has been classified as Amber List (Moderate Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.30 KCNE1 Seb Lunke reviewed gene: KCNE1: Rating: AMBER; Mode of pathogenicity: None; Publications: 31527855, 30936463, 31983240; Phenotypes: Long QT syndrome 5, MIM# 613695, Jervell and Lange-Nielsen syndrome 2, MIM# 612347, Acquired LQTS; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mackenzie's Mission_Reproductive Carrier Screening v0.30 PIBF1 Sarah Righetti reviewed gene: PIBF1: Rating: AMBER; Mode of pathogenicity: None; Publications: 26167768, 29695797, 30858804, 33004012; Phenotypes: JOUBERT SYNDROME 33, OMIM# 617767; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mackenzie's Mission_Reproductive Carrier Screening v0.30 PIBF1 Sarah Righetti Deleted their review
Mackenzie's Mission_Reproductive Carrier Screening v0.30 B9D1 Seb Lunke Marked gene: B9D1 as ready
Mackenzie's Mission_Reproductive Carrier Screening v0.30 B9D1 Seb Lunke Gene: b9d1 has been classified as Amber List (Moderate Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.30 B9D1 Seb Lunke Classified gene: B9D1 as Amber List (moderate evidence)
Mackenzie's Mission_Reproductive Carrier Screening v0.30 B9D1 Seb Lunke Gene: b9d1 has been classified as Amber List (Moderate Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.29 ACADM Seb Lunke Marked gene: ACADM as ready
Mackenzie's Mission_Reproductive Carrier Screening v0.29 ACADM Seb Lunke Gene: acadm has been classified as Green List (High Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.29 ACADM Seb Lunke Classified gene: ACADM as Green List (high evidence)
Mackenzie's Mission_Reproductive Carrier Screening v0.29 ACADM Seb Lunke Gene: acadm has been classified as Green List (High Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.28 ACADM Sarah Righetti gene: ACADM was added
gene: ACADM was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Expert Review
Mode of inheritance for gene: ACADM was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ACADM were set to Acyl-CoA dehydrogenase, medium chain, deficiency of, MIM #201450
Review for gene: ACADM was set to GREEN
Added comment: MUTATIONAL AND CLINICAL SPECTRUM: Most common variant is NM_000016.6:c.985A>G p.K329E (p.K304E in mature protein) seen hom/chet in patients with classical MCAD deficiency, also seen chet in asymptomatic siblings. Beware existence of pseudodeficiency alleles (e.g. chet c.199T>C p.Y67H) where individuals have reduced enzymatic activity and so are positive on NBS but do not usually have clinical symptoms.

TREATMENT: Covered on NBS, generally very successful treatment with mainly dietary management. However 3 neonates in past year at WCH who have had cardiac/respiratory arrests before 48 hours (i.e. prior to NBS results being available). There are a number of babies who have died or had brain damage as a result of hypoglycemia prior to the test being taken.

Summary: GREEN; meets MM panel inclusion criteria where early diagnosis can lead to more effective treatment. Counsel accordingly.
Sources: Expert Review
Mackenzie's Mission_Reproductive Carrier Screening v0.28 B9D1 Sarah Righetti gene: B9D1 was added
gene: B9D1 was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Literature
Mode of inheritance for gene: B9D1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: B9D1 were set to 24886560; 21493627; 25920555
Phenotypes for gene: B9D1 were set to Meckel syndrome 9, MIM# 614209; Joubert syndrome 27, MIM# 617120
Added comment: PMID: 24886560 - 2 unrelated patients with mild Joubert syndrome (1 hom missense, 1 chet inframe deletion/missense). Authors suggest biallelic null variants are lethal.

PMID: 21493627 - 1 fetus with Meckel syndrome and chet for a splice/gene deletion. The splice variant proven to result in exon skipping -> PTC, but the deletion spans a large region including 18 other genes. Patient also had an additional variant in CEP290 called LP. Authors perform functional studies on patient cells but given the large deletion/CEP290 variant, results cannot be used.

PMID 25920555 - another report of digenic inheritance - not usable, patient was only heterozygous for a single B9D1 variant

Summary: 2 unrelated patients, AMBER
Sources: Literature
Mackenzie's Mission_Reproductive Carrier Screening v0.28 TRAC Seb Lunke Marked gene: TRAC as ready
Mackenzie's Mission_Reproductive Carrier Screening v0.28 TRAC Seb Lunke Gene: trac has been classified as Amber List (Moderate Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.28 TRAC Seb Lunke Classified gene: TRAC as Amber List (moderate evidence)
Mackenzie's Mission_Reproductive Carrier Screening v0.28 TRAC Seb Lunke Gene: trac has been classified as Amber List (Moderate Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.27 ABCC6 Seb Lunke Marked gene: ABCC6 as ready
Mackenzie's Mission_Reproductive Carrier Screening v0.27 ABCC6 Seb Lunke Gene: abcc6 has been classified as Green List (High Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.27 SERPINA1 Seb Lunke Marked gene: SERPINA1 as ready
Mackenzie's Mission_Reproductive Carrier Screening v0.27 SERPINA1 Seb Lunke Gene: serpina1 has been classified as Green List (High Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.27 PIBF1 Sarah Righetti gene: PIBF1 was added
gene: PIBF1 was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Literature
Mode of inheritance for gene: PIBF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIBF1 were set to 26167768; 29695797; 30858804; 33004012
Phenotypes for gene: PIBF1 were set to OMIM# 617767: JOUBERT SYNDROME 33; JBTS33
Review for gene: PIBF1 was set to AMBER
Added comment: Seven Joubert families, four with the same founder variant (all Hutterite)
Sources: Literature
Mendeliome v0.4947 PIBF1 Sarah Righetti reviewed gene: PIBF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33004012; Phenotypes: ; Mode of inheritance: None
Mackenzie's Mission_Reproductive Carrier Screening v0.27 TRAC Sarah Righetti changed review comment from: Two individuals from two unrelated consanguinous families with same homozygous truncating variant; to: Two unrelated individuals from two consanguinous families of Pakistani origin with same homozygous truncating variant
Mackenzie's Mission_Reproductive Carrier Screening v0.27 TRAC Sarah Righetti reviewed gene: TRAC: Rating: AMBER; Mode of pathogenicity: None; Publications: 21206088; Phenotypes: Immunodeficiency 7, TCR-alpha/beta deficient; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mackenzie's Mission_Reproductive Carrier Screening v0.27 ABCC6 Sarah Righetti reviewed gene: ABCC6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mackenzie's Mission_Reproductive Carrier Screening v0.27 KCNE1 Sarah Righetti reviewed gene: KCNE1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mackenzie's Mission_Reproductive Carrier Screening v0.27 SERPINA1 Sarah Righetti reviewed gene: SERPINA1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Emphysema-cirrhosis, due to AAT deficiency; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mackenzie's Mission_Reproductive Carrier Screening v0.27 CIB2 Seb Lunke Marked gene: CIB2 as ready
Mackenzie's Mission_Reproductive Carrier Screening v0.27 CIB2 Seb Lunke Gene: cib2 has been classified as Red List (Low Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.27 CIB2 Seb Lunke Classified gene: CIB2 as Red List (low evidence)
Mackenzie's Mission_Reproductive Carrier Screening v0.27 CIB2 Seb Lunke Gene: cib2 has been classified as Red List (Low Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.26 CBS Seb Lunke Marked gene: CBS as ready
Mackenzie's Mission_Reproductive Carrier Screening v0.26 CBS Seb Lunke Gene: cbs has been classified as Red List (Low Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.26 CBS Seb Lunke Classified gene: CBS as Red List (low evidence)
Mackenzie's Mission_Reproductive Carrier Screening v0.26 CBS Seb Lunke Gene: cbs has been classified as Red List (Low Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.25 CBS Seb Lunke reviewed gene: CBS: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.228 MYH2 Zornitza Stark Marked gene: MYH2 as ready
Arthrogryposis v0.228 MYH2 Zornitza Stark Gene: myh2 has been classified as Green List (High Evidence).
Arthrogryposis v0.228 MYH2 Zornitza Stark Phenotypes for gene: MYH2 were changed from to Proximal myopathy and ophthalmoplegia, MIM# 605637
Arthrogryposis v0.227 MYH2 Zornitza Stark Publications for gene: MYH2 were set to
Arthrogryposis v0.226 MYH2 Zornitza Stark Mode of inheritance for gene: MYH2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.225 MYH2 Zornitza Stark reviewed gene: MYH2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20418530, 15548556, 24193343, 11114175, 23489661, 32578970, 29934118, 28729039, 27490141, 27177998, 17434305; Phenotypes: Proximal myopathy and ophthalmoplegia, MIM# 605637; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4947 MYH2 Zornitza Stark Marked gene: MYH2 as ready
Mendeliome v0.4947 MYH2 Zornitza Stark Gene: myh2 has been classified as Green List (High Evidence).
Mendeliome v0.4947 MYH2 Zornitza Stark Phenotypes for gene: MYH2 were changed from to Proximal myopathy and ophthalmoplegia, MIM# 605637
Mendeliome v0.4946 MYH2 Zornitza Stark Publications for gene: MYH2 were set to
Mendeliome v0.4945 MYH2 Zornitza Stark Mode of inheritance for gene: MYH2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4944 MYH2 Zornitza Stark reviewed gene: MYH2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20418530, 15548556, 24193343, 11114175, 23489661, 32578970, 29934118, 28729039, 27490141, 27177998; Phenotypes: Proximal myopathy and ophthalmoplegia, MIM# 605637; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Arthrogryposis v0.225 KLHL41 Zornitza Stark Marked gene: KLHL41 as ready
Arthrogryposis v0.225 KLHL41 Zornitza Stark Gene: klhl41 has been classified as Green List (High Evidence).
Arthrogryposis v0.225 KLHL41 Zornitza Stark Phenotypes for gene: KLHL41 were changed from to Nemaline myopathy 9, MIM# 615731
Arthrogryposis v0.224 KLHL41 Zornitza Stark Publications for gene: KLHL41 were set to
Arthrogryposis v0.223 KLHL41 Zornitza Stark Mode of inheritance for gene: KLHL41 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.222 KLHL41 Zornitza Stark reviewed gene: KLHL41: Rating: GREEN; Mode of pathogenicity: None; Publications: 24268659, 30986853, 28939701, 28826497; Phenotypes: Nemaline myopathy 9, MIM# 615731; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4944 KLHL41 Zornitza Stark Marked gene: KLHL41 as ready
Mendeliome v0.4944 KLHL41 Zornitza Stark Gene: klhl41 has been classified as Green List (High Evidence).
Mendeliome v0.4944 KLHL41 Zornitza Stark Phenotypes for gene: KLHL41 were changed from to Nemaline myopathy 9, MIM# 615731
Mendeliome v0.4943 KLHL41 Zornitza Stark Publications for gene: KLHL41 were set to
Mendeliome v0.4942 KLHL41 Zornitza Stark Mode of inheritance for gene: KLHL41 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4941 KLHL41 Zornitza Stark reviewed gene: KLHL41: Rating: GREEN; Mode of pathogenicity: None; Publications: 24268659, 30986853, 28939701, 28826497; Phenotypes: Nemaline myopathy 9, MIM# 615731; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Multiple pterygium syndrome_Fetal akinesia sequence v0.6 KLHL40 Zornitza Stark Marked gene: KLHL40 as ready
Multiple pterygium syndrome_Fetal akinesia sequence v0.6 KLHL40 Zornitza Stark Gene: klhl40 has been classified as Green List (High Evidence).
Multiple pterygium syndrome_Fetal akinesia sequence v0.6 KLHL40 Zornitza Stark Tag founder tag was added to gene: KLHL40.
Multiple pterygium syndrome_Fetal akinesia sequence v0.6 KLHL40 Zornitza Stark Phenotypes for gene: KLHL40 were changed from to Nemaline myopathy 8, autosomal recessive, MIM# 615348
Multiple pterygium syndrome_Fetal akinesia sequence v0.5 KLHL40 Zornitza Stark Publications for gene: KLHL40 were set to
Multiple pterygium syndrome_Fetal akinesia sequence v0.4 KLHL40 Zornitza Stark Mode of inheritance for gene: KLHL40 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Multiple pterygium syndrome_Fetal akinesia sequence v0.3 KLHL40 Zornitza Stark reviewed gene: KLHL40: Rating: GREEN; Mode of pathogenicity: None; Publications: 23746549, 24960163, 32352246, 31908664, 27528495; Phenotypes: Nemaline myopathy 8, autosomal recessive, MIM# 615348; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4941 KLHL40 Zornitza Stark Tag founder tag was added to gene: KLHL40.
Mendeliome v0.4941 KLHL40 Zornitza Stark Marked gene: KLHL40 as ready
Mendeliome v0.4941 KLHL40 Zornitza Stark Gene: klhl40 has been classified as Green List (High Evidence).
Mendeliome v0.4941 KLHL40 Zornitza Stark Phenotypes for gene: KLHL40 were changed from to Nemaline myopathy 8, autosomal recessive, MIM# 615348
Mendeliome v0.4940 KLHL40 Zornitza Stark Publications for gene: KLHL40 were set to
Mendeliome v0.4939 KLHL40 Zornitza Stark Mode of inheritance for gene: KLHL40 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4938 KLHL40 Zornitza Stark reviewed gene: KLHL40: Rating: GREEN; Mode of pathogenicity: None; Publications: 23746549, 24960163, 32352246, 31908664, 27528495; Phenotypes: Nemaline myopathy 8, autosomal recessive, MIM# 615348; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.222 KLHL40 Zornitza Stark Tag founder tag was added to gene: KLHL40.
Arthrogryposis v0.222 KLHL40 Zornitza Stark Marked gene: KLHL40 as ready
Arthrogryposis v0.222 KLHL40 Zornitza Stark Gene: klhl40 has been classified as Green List (High Evidence).
Arthrogryposis v0.222 KLHL40 Zornitza Stark Phenotypes for gene: KLHL40 were changed from to Nemaline myopathy 8, autosomal recessive, MIM# 615348
Arthrogryposis v0.221 KLHL40 Zornitza Stark Publications for gene: KLHL40 were set to
Arthrogryposis v0.220 KLHL40 Zornitza Stark Mode of inheritance for gene: KLHL40 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.219 KLHL40 Zornitza Stark reviewed gene: KLHL40: Rating: GREEN; Mode of pathogenicity: None; Publications: 23746549, 24960163, 32352246, 31908664, 27528495; Phenotypes: Nemaline myopathy 8, autosomal recessive, MIM# 615348; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4938 MYO18B Zornitza Stark Marked gene: MYO18B as ready
Mendeliome v0.4938 MYO18B Zornitza Stark Gene: myo18b has been classified as Green List (High Evidence).
Mendeliome v0.4938 MYO18B Zornitza Stark Phenotypes for gene: MYO18B were changed from to Klippel-Feil syndrome 4, autosomal recessive, with myopathy and facial dysmorphism, MIM# 616549
Mendeliome v0.4937 MYO18B Zornitza Stark Publications for gene: MYO18B were set to
Mendeliome v0.4936 MYO18B Zornitza Stark Mode of inheritance for gene: MYO18B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4935 MYO18B Zornitza Stark reviewed gene: MYO18B: Rating: GREEN; Mode of pathogenicity: None; Publications: 25748484, 27858739, 32637634, 32184166, 27879346; Phenotypes: Klippel-Feil syndrome 4, autosomal recessive, with myopathy and facial dysmorphism, MIM# 616549; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Incidentalome v0.47 GLA Zornitza Stark Marked gene: GLA as ready
Incidentalome v0.47 GLA Zornitza Stark Gene: gla has been classified as Green List (High Evidence).
Incidentalome v0.47 GLA Zornitza Stark Phenotypes for gene: GLA were changed from to Fabry disease 301500; Fabry disease, cardiac variant 301500
Incidentalome v0.46 GLA Zornitza Stark Publications for gene: GLA were set to
Incidentalome v0.45 GLA Zornitza Stark Mode of pathogenicity for gene: GLA was changed from to Other
Incidentalome v0.44 GLA Zornitza Stark Mode of inheritance for gene: GLA 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)
Incidentalome v0.43 GLA Elena Savva reviewed gene: GLA: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 8878432, 31613176; Phenotypes: Fabry disease 301500, Fabry disease, cardiac variant 301500; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Genetic Epilepsy v0.880 ADGRV1 Zornitza Stark Marked gene: ADGRV1 as ready
Genetic Epilepsy v0.880 ADGRV1 Zornitza Stark Gene: adgrv1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.880 ADGRV1 Zornitza Stark changed review comment from: Bi-allelic variants in this gene are associated with Usher syndrome.

Some evidence that variants in this gene are implicated in epilepsy, based on animal model, presence in the recurrent 5q14.3 deletion, and over-representation of rare variants in myoclonic epilepsy cohorts (29266188) and identification in individual cases (29261713; 32962041). However, some of the variants do not meet pathogenicity criteria (present in pop datasets, no segregation information available) and contribution may be under a polygenic model.
Sources: Expert Review; to: Bi-allelic variants in this gene are associated with Usher syndrome.

Some evidence that mono-allelic variants in this gene are implicated in epilepsy, based on animal model, presence in the recurrent 5q14.3 deletion, and over-representation of rare variants in myoclonic epilepsy cohorts (29266188) and identification in individual cases (29261713; 32962041). However, some of the variants do not meet pathogenicity criteria (present in pop datasets, no segregation information available) and contribution may be under a polygenic model.
Sources: Expert Review
Genetic Epilepsy v0.880 ADGRV1 Zornitza Stark gene: ADGRV1 was added
gene: ADGRV1 was added to Genetic Epilepsy. Sources: Expert Review
Mode of inheritance for gene: ADGRV1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ADGRV1 were set to 29266188; 29261713; 32962041
Phenotypes for gene: ADGRV1 were set to Myoclonic epilepsy; febrile seizures; epilepsy
Review for gene: ADGRV1 was set to RED
Added comment: Bi-allelic variants in this gene are associated with Usher syndrome.

Some evidence that variants in this gene are implicated in epilepsy, based on animal model, presence in the recurrent 5q14.3 deletion, and over-representation of rare variants in myoclonic epilepsy cohorts (29266188) and identification in individual cases (29261713; 32962041). However, some of the variants do not meet pathogenicity criteria (present in pop datasets, no segregation information available) and contribution may be under a polygenic model.
Sources: Expert Review
Mendeliome v0.4935 MEGF10 Zornitza Stark Marked gene: MEGF10 as ready
Mendeliome v0.4935 MEGF10 Zornitza Stark Gene: megf10 has been classified as Green List (High Evidence).
Mendeliome v0.4935 MEGF10 Zornitza Stark Phenotypes for gene: MEGF10 were changed from to Myopathy, areflexia, respiratory distress, and dysphagia, early-onset, MIM# 614399
Mendeliome v0.4934 MEGF10 Zornitza Stark Publications for gene: MEGF10 were set to
Mendeliome v0.4933 MEGF10 Zornitza Stark Mode of inheritance for gene: MEGF10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4932 MEGF10 Zornitza Stark reviewed gene: MEGF10: Rating: GREEN; Mode of pathogenicity: None; Publications: 22101682, 22371254, 30802937; Phenotypes: Myopathy, areflexia, respiratory distress, and dysphagia, early-onset, MIM# 614399; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Heart Defect v0.73 ACTC1 Zornitza Stark Marked gene: ACTC1 as ready
Congenital Heart Defect v0.73 ACTC1 Zornitza Stark Gene: actc1 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.73 ACTC1 Zornitza Stark Phenotypes for gene: ACTC1 were changed from to Atrial septal defect 5, MIM# 612794
Congenital Heart Defect v0.72 ACTC1 Zornitza Stark Publications for gene: ACTC1 were set to
Congenital Heart Defect v0.71 ACTC1 Zornitza Stark Mode of inheritance for gene: ACTC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.70 ACTC1 Zornitza Stark reviewed gene: ACTC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 17947298, 31430208; Phenotypes: Atrial septal defect 5, MIM# 612794; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal Ciliopathies and Nephronophthisis v0.124 WDPCP Zornitza Stark Publications for gene: WDPCP were set to 20671153; 25427950
Renal Ciliopathies and Nephronophthisis v0.123 WDPCP Zornitza Stark Classified gene: WDPCP as Green List (high evidence)
Renal Ciliopathies and Nephronophthisis v0.123 WDPCP Zornitza Stark Gene: wdpcp has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v0.122 WDPCP Zornitza Stark edited their review of gene: WDPCP: Added comment: Four families reported with ciliopathy phenotypes, including BBS, OFD, syndromic retinopathy.; Changed rating: GREEN; Changed publications: 20671153, 25427950, 32055034, 29588463, 28289185
Polydactyly v0.180 WDPCP Zornitza Stark Publications for gene: WDPCP were set to 20671153; 25427950
Polydactyly v0.179 WDPCP Zornitza Stark Classified gene: WDPCP as Green List (high evidence)
Polydactyly v0.179 WDPCP Zornitza Stark Gene: wdpcp has been classified as Green List (High Evidence).
Polydactyly v0.178 WDPCP Zornitza Stark edited their review of gene: WDPCP: Added comment: Four families reported with ciliopathy phenotypes, including BBS, OFD, syndromic retinopathy.; Changed rating: GREEN; Changed publications: 20671153, 25427950, 32055034, 29588463, 28289185
Mendeliome v0.4932 WDPCP Zornitza Stark Publications for gene: WDPCP were set to 20671153; 25427950
Mendeliome v0.4931 WDPCP Zornitza Stark Classified gene: WDPCP as Green List (high evidence)
Mendeliome v0.4931 WDPCP Zornitza Stark Gene: wdpcp has been classified as Green List (High Evidence).
Mendeliome v0.4930 WDPCP Zornitza Stark commented on gene: WDPCP: Four families reported with ciliopathy phenotypes, including BBS, OFD, syndromic retinopathy.
Mendeliome v0.4930 WDPCP Zornitza Stark edited their review of gene: WDPCP: Changed rating: GREEN; Changed publications: 20671153, 25427950, 32055034, 29588463, 28289185; Changed phenotypes: Bardet-Biedl syndrome 15, MIM# 615992, OFD, Congenital heart defects, hamartomas of tongue, and polysyndactyly, 217085
Ciliopathies v0.212 WDPCP Zornitza Stark Phenotypes for gene: WDPCP were changed from Bardet-Biedl syndrome 15, MIM# 615992; OFD; Congenital heart defects, hamartomas of tongue, and polysyndactyly, 217085 to Bardet-Biedl syndrome 15, MIM# 615992; OFD; Congenital heart defects, hamartomas of tongue, and polysyndactyly, 217085
Ciliopathies v0.212 WDPCP Zornitza Stark Phenotypes for gene: WDPCP were changed from Bardet-Biedl syndrome 15, MIM# 615992 to Bardet-Biedl syndrome 15, MIM# 615992; OFD; Congenital heart defects, hamartomas of tongue, and polysyndactyly, 217085
Ciliopathies v0.211 WDPCP Zornitza Stark Publications for gene: WDPCP were set to 20671153; 25427950
Ciliopathies v0.210 WDPCP Zornitza Stark Classified gene: WDPCP as Green List (high evidence)
Ciliopathies v0.210 WDPCP Zornitza Stark Gene: wdpcp has been classified as Green List (High Evidence).
Ciliopathies v0.209 WDPCP Zornitza Stark edited their review of gene: WDPCP: Added comment: Four families reported with ciliopathy phenotypes, including BBS, OFD, syndromic retinopathy.; Changed rating: GREEN; Changed publications: 20671153, 25427950, 32055034, 29588463, 28289185
Skeletal dysplasia v0.56 WDPCP Zornitza Stark Classified gene: WDPCP as Green List (high evidence)
Skeletal dysplasia v0.56 WDPCP Zornitza Stark Gene: wdpcp has been classified as Green List (High Evidence).
Skeletal dysplasia v0.55 WDPCP Zornitza Stark changed review comment from: Two families reported; the first one with a BBS phenotype, and in the second one affected individual had polysyndactyly and tongue hamartomas, so phenotype consistent with OFD rather than BBS.; to: Four families reported with ciliopathy phenotypes, including BBS, OFD, syndromic retinopathy.
Intellectual disability syndromic and non-syndromic v0.3073 WDPCP Zornitza Stark Publications for gene: WDPCP were set to
Skeletal dysplasia v0.55 WDPCP Zornitza Stark edited their review of gene: WDPCP: Changed rating: GREEN; Changed publications: 20671153, 25427950, 32055034, 29588463, 28289185
Intellectual disability syndromic and non-syndromic v0.3072 WDPCP Zornitza Stark Classified gene: WDPCP as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3072 WDPCP Zornitza Stark Gene: wdpcp has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3071 WDPCP Zornitza Stark edited their review of gene: WDPCP: Changed rating: GREEN
Intellectual disability syndromic and non-syndromic v0.3071 WDPCP Zornitza Stark changed review comment from: Two families reported; the first one with a BBS phenotype, and in the second one affected individual had polysyndactyly and tongue hamartomas, so phenotype consistent with OFD rather than BBS.; to: At least four families reported with ciliopathy phenotypes (BBS, OFD, syndromic retinopathy).
Intellectual disability syndromic and non-syndromic v0.3071 WDPCP Zornitza Stark edited their review of gene: WDPCP: Changed publications: 20671153, 25427950, 32055034, 29588463, 28289185
Skeletal dysplasia v0.55 WDPCP Zornitza Stark Publications for gene: WDPCP were set to 28289185; 27158779; 25427950
Skeletal dysplasia v0.54 WDPCP Zornitza Stark Marked gene: WDPCP as ready
Skeletal dysplasia v0.54 WDPCP Zornitza Stark Gene: wdpcp has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v0.54 WDPCP Zornitza Stark Classified gene: WDPCP as Amber List (moderate evidence)
Skeletal dysplasia v0.54 WDPCP Zornitza Stark Gene: wdpcp has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3071 WDPCP Zornitza Stark Mode of inheritance for gene: WDPCP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3070 WDPCP Zornitza Stark Classified gene: WDPCP as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3070 WDPCP Zornitza Stark Gene: wdpcp has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v0.53 WDPCP Zornitza Stark reviewed gene: WDPCP: Rating: AMBER; Mode of pathogenicity: None; Publications: 20671153, 25427950; Phenotypes: Bardet-Biedl syndrome 15, MIM# 615992, OFD, Congenital heart defects, hamartomas of tongue, and polysyndactyly, 217085; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3069 WDPCP Zornitza Stark reviewed gene: WDPCP: Rating: AMBER; Mode of pathogenicity: None; Publications: 20671153, 25427950; Phenotypes: Bardet-Biedl syndrome 15, MIM# 615992, OFD, Congenital heart defects, hamartomas of tongue, and polysyndactyly, 217085; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.122 WDPCP Zornitza Stark Marked gene: WDPCP as ready
Renal Ciliopathies and Nephronophthisis v0.122 WDPCP Zornitza Stark Gene: wdpcp has been classified as Amber List (Moderate Evidence).
Renal Ciliopathies and Nephronophthisis v0.122 WDPCP Zornitza Stark Phenotypes for gene: WDPCP were changed from to Bardet-Biedl syndrome 15, MIM# 615992; OFD; Congenital heart defects, hamartomas of tongue, and polysyndactyly, 217085
Renal Ciliopathies and Nephronophthisis v0.121 WDPCP Zornitza Stark Publications for gene: WDPCP were set to
Renal Ciliopathies and Nephronophthisis v0.120 WDPCP Zornitza Stark Mode of inheritance for gene: WDPCP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.119 WDPCP Zornitza Stark Classified gene: WDPCP as Amber List (moderate evidence)
Renal Ciliopathies and Nephronophthisis v0.119 WDPCP Zornitza Stark Gene: wdpcp has been classified as Amber List (Moderate Evidence).
Renal Ciliopathies and Nephronophthisis v0.118 WDPCP Zornitza Stark reviewed gene: WDPCP: Rating: AMBER; Mode of pathogenicity: None; Publications: 20671153, 25427950; Phenotypes: Bardet-Biedl syndrome 15, MIM# 615992, OFD, Congenital heart defects, hamartomas of tongue, and polysyndactyly, 217085; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.178 WDPCP Zornitza Stark Phenotypes for gene: WDPCP were changed from to Bardet-Biedl syndrome 15, MIM# 615992; OFD; Congenital heart defects, hamartomas of tongue, and polysyndactyly, 217085
Polydactyly v0.177 WDPCP Zornitza Stark Publications for gene: WDPCP were set to
Polydactyly v0.176 WDPCP Zornitza Stark Classified gene: WDPCP as Amber List (moderate evidence)
Polydactyly v0.176 WDPCP Zornitza Stark Gene: wdpcp has been classified as Amber List (Moderate Evidence).
Polydactyly v0.175 WDPCP Zornitza Stark reviewed gene: WDPCP: Rating: AMBER; Mode of pathogenicity: None; Publications: 20671153, 25427950; Phenotypes: Bardet-Biedl syndrome 15, MIM# 615992, OFD, Congenital heart defects, hamartomas of tongue, and polysyndactyly, 217085; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4930 WDPCP Zornitza Stark Marked gene: WDPCP as ready
Mendeliome v0.4930 WDPCP Zornitza Stark Gene: wdpcp has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4930 WDPCP Zornitza Stark Phenotypes for gene: WDPCP were changed from Bardet-Biedl syndrome 15, MIM# 615992; OFD; Congenital heart defects, hamartomas of tongue, and polysyndactyly, 217085 to Bardet-Biedl syndrome 15, MIM# 615992; OFD; Congenital heart defects, hamartomas of tongue, and polysyndactyly, 217085
Mendeliome v0.4930 WDPCP Zornitza Stark Phenotypes for gene: WDPCP were changed from to Bardet-Biedl syndrome 15, MIM# 615992; OFD; Congenital heart defects, hamartomas of tongue, and polysyndactyly, 217085
Mendeliome v0.4929 WDPCP Zornitza Stark Publications for gene: WDPCP were set to
Mendeliome v0.4928 WDPCP Zornitza Stark Mode of inheritance for gene: WDPCP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4927 WDPCP Zornitza Stark Classified gene: WDPCP as Amber List (moderate evidence)
Mendeliome v0.4927 WDPCP Zornitza Stark Gene: wdpcp has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4926 WDPCP Zornitza Stark reviewed gene: WDPCP: Rating: AMBER; Mode of pathogenicity: None; Publications: 20671153, 25427950; Phenotypes: Bardet-Biedl syndrome 15, MIM# 615992, OFD; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Syndromic Retinopathy v0.148 TUBGCP6 Zornitza Stark Marked gene: TUBGCP6 as ready
Syndromic Retinopathy v0.148 TUBGCP6 Zornitza Stark Gene: tubgcp6 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.148 TUBGCP6 Zornitza Stark Phenotypes for gene: TUBGCP6 were changed from to Microcephaly and chorioretinopathy, autosomal recessive, 1, MIM# 251270
Syndromic Retinopathy v0.147 TUBGCP6 Zornitza Stark Publications for gene: TUBGCP6 were set to
Syndromic Retinopathy v0.146 TUBGCP6 Zornitza Stark Mode of inheritance for gene: TUBGCP6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Syndromic Retinopathy v0.145 TUBGCP6 Zornitza Stark reviewed gene: TUBGCP6: Rating: GREEN; Mode of pathogenicity: None; Publications: 22279524, 25344692; Phenotypes: Microcephaly and chorioretinopathy, autosomal recessive, 1, MIM# 251270; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4926 TUBGCP4 Zornitza Stark Marked gene: TUBGCP4 as ready
Mendeliome v0.4926 TUBGCP4 Zornitza Stark Gene: tubgcp4 has been classified as Green List (High Evidence).
Mendeliome v0.4926 TUBGCP4 Zornitza Stark Phenotypes for gene: TUBGCP4 were changed from to Microcephaly and chorioretinopathy, autosomal recessive, 3, MIM# 616335
Mendeliome v0.4925 TUBGCP4 Zornitza Stark Publications for gene: TUBGCP4 were set to
Mendeliome v0.4924 TUBGCP4 Zornitza Stark Mode of inheritance for gene: TUBGCP4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4923 TUBGCP4 Zornitza Stark reviewed gene: TUBGCP4: Rating: GREEN; Mode of pathogenicity: None; Publications: 25817018, 32270730; Phenotypes: Microcephaly and chorioretinopathy, autosomal recessive, 3, MIM# 616335; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Syndromic Retinopathy v0.145 TUBGCP4 Zornitza Stark Marked gene: TUBGCP4 as ready
Syndromic Retinopathy v0.145 TUBGCP4 Zornitza Stark Gene: tubgcp4 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.145 TUBGCP4 Zornitza Stark Phenotypes for gene: TUBGCP4 were changed from to Microcephaly and chorioretinopathy, autosomal recessive, 3, MIM# 616335
Syndromic Retinopathy v0.144 TUBGCP4 Zornitza Stark Publications for gene: TUBGCP4 were set to
Syndromic Retinopathy v0.143 TUBGCP4 Zornitza Stark Mode of inheritance for gene: TUBGCP4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Syndromic Retinopathy v0.142 TUBGCP4 Zornitza Stark reviewed gene: TUBGCP4: Rating: GREEN; Mode of pathogenicity: None; Publications: 25817018, 32270730; Phenotypes: Microcephaly and chorioretinopathy, autosomal recessive, 3, MIM# 616335; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Syndromic Retinopathy v0.142 TRNT1 Zornitza Stark changed review comment from: The disorders associated with this gene likely represent a spectrum rather than distinct conditions, therefore gene-disease association evidence assessed across publications. . RP/retinal dysfunction reported in more than 3 families, supportive functional data.; to: The disorders associated with this gene likely represent a spectrum rather than distinct conditions, therefore gene-disease association evidence assessed across publications. RP/retinal dysfunction reported in more than 3 families, supportive functional data.
Syndromic Retinopathy v0.142 TRNT1 Zornitza Stark changed review comment from: The disorders associated with this gene likely represent a spectrum. RP/retinal dysfunction reported in more than 3 families, supportive functional data.; to: The disorders associated with this gene likely represent a spectrum rather than distinct conditions, therefore gene-disease association evidence assessed across publications. . RP/retinal dysfunction reported in more than 3 families, supportive functional data.
Skeletal Ciliopathies v0.56 DYNC2LI1 Zornitza Stark Marked gene: DYNC2LI1 as ready
Skeletal Ciliopathies v0.56 DYNC2LI1 Zornitza Stark Gene: dync2li1 has been classified as Green List (High Evidence).
Skeletal Ciliopathies v0.56 DYNC2LI1 Zornitza Stark Phenotypes for gene: DYNC2LI1 were changed from to Short-rib thoracic dysplasia 15 with polydactyly (MIM#617088)
Skeletal Ciliopathies v0.55 DYNC2LI1 Zornitza Stark Publications for gene: DYNC2LI1 were set to
Skeletal Ciliopathies v0.54 DYNC2LI1 Zornitza Stark Mode of inheritance for gene: DYNC2LI1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Skeletal Ciliopathies v0.53 DYNC2LI1 Zornitza Stark reviewed gene: DYNC2LI1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33030252; Phenotypes: Short-rib thoracic dysplasia 15 with polydactyly (MIM#617088); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4923 DYNC2LI1 Zornitza Stark Marked gene: DYNC2LI1 as ready
Mendeliome v0.4923 DYNC2LI1 Zornitza Stark Gene: dync2li1 has been classified as Green List (High Evidence).
Mendeliome v0.4923 DYNC2LI1 Zornitza Stark Phenotypes for gene: DYNC2LI1 were changed from to Short-rib thoracic dysplasia 15 with polydactyly (MIM#617088)
Mendeliome v0.4922 DYNC2LI1 Zornitza Stark Publications for gene: DYNC2LI1 were set to
Mendeliome v0.4921 DYNC2LI1 Zornitza Stark Mode of inheritance for gene: DYNC2LI1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4920 SLC20A2 Zornitza Stark Phenotypes for gene: SLC20A2 were changed from Basal ganglia calcification, idiopathic, 1, MIM# 213600 to Basal ganglia calcification, idiopathic, 1, MIM# 213600; ?hereditary multiple exostoses
Mendeliome v0.4919 SLC20A2 Zornitza Stark Publications for gene: SLC20A2 were set to 22327515; 23334463
Intellectual disability syndromic and non-syndromic v0.3069 TRAPPC9 Zornitza Stark Tag SV/CNV tag was added to gene: TRAPPC9.
Intellectual disability syndromic and non-syndromic v0.3069 TRAPPC9 Zornitza Stark Publications for gene: TRAPPC9 were set to 30853973
Intellectual disability syndromic and non-syndromic v0.3068 TRAPPC9 Zornitza Stark reviewed gene: TRAPPC9: Rating: GREEN; Mode of pathogenicity: None; Publications: 22549410, 20004765, 20004763, 30853973, 29187737; Phenotypes: Mental retardation, autosomal recessive 13, MIM# 613192; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.489 TRAPPC9 Zornitza Stark Publications for gene: TRAPPC9 were set to 22549410; 20004765; 20004763; 30853973
Microcephaly v0.488 TRAPPC9 Zornitza Stark Tag SV/CNV tag was added to gene: TRAPPC9.
Microcephaly v0.488 TRAPPC9 Zornitza Stark edited their review of gene: TRAPPC9: Added comment: Note multiple intragenic CNVs reported for this gene.; Changed publications: 22549410, 20004765, 20004763, 30853973, 29187737
Mendeliome v0.4918 TRAPPC9 Zornitza Stark Publications for gene: TRAPPC9 were set to 22549410; 20004765; 20004763; 30853973
Mendeliome v0.4917 TRAPPC9 Zornitza Stark Tag SV/CNV tag was added to gene: TRAPPC9.
Mendeliome v0.4917 DYNC2LI1 Ain Roesley reviewed gene: DYNC2LI1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33030252; Phenotypes: Short-rib thoracic dysplasia 15 with polydactyly (MIM#617088); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4917 SLC20A2 Elena Savva reviewed gene: SLC20A2: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID 24209445, 23437308, 32705272, 27943094; Phenotypes: Basal ganglia calcification, idiopathic, 1213600, ?hereditary multiple exostoses; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Red cell disorders v0.2 Zornitza Stark Panel status changed from deleted to public
Red cell disorders v0.1 SF3B1 Zornitza Stark Added phenotypes 605590 Refractory anaemia with ring sideroblasts for gene: SF3B1
Publications for gene SF3B1 were updated from 21995386; 28188970 to 28188970; 21995386
Red cell disorders v0.1 HBE1 Zornitza Stark Added phenotypes Epsilon-gamma-delta-beta thalassaemia for gene: HBE1
Red cell disorders v0.1 GPX1 Zornitza Stark Added phenotypes 614164 Hemolytic anemia due to glutathione peroxidase deficiency for gene: GPX1
Red cell disorders v0.1 FTCD Zornitza Stark Added phenotypes 229100 Glutamate formiminotransferase deficiency for gene: FTCD
Red cell disorders v0.1 DKC1 Zornitza Stark Added phenotypes 305000 Dyskeratosis congenita, X-linked for gene: DKC1
Red cell disorders v0.1 CYB5A Zornitza Stark Added phenotypes 250790 Methemoglobinemia and ambiguous genitalia for gene: CYB5A
Publications for gene CYB5A were updated from 20080843; 8168836 to 8168836; 20080843
Red cell disorders v0.1 ATRX Zornitza Stark Added phenotypes 301040 Alpha-thalassemia/mental retardation syndrome for gene: ATRX
Publications for gene ATRX were updated from 19444090; 11449489; 17579672 to 19444090; 17579672; 11449489
Red cell disorders v0.1 TSR2 Zornitza Stark Added phenotypes 300946 ?Diamond-Blackfan anemia 14 with mandibulofacial dysostosis; ?Diamond-Blackfan anemia 14 with mandibulofacial dysostosis, 300946 for gene: TSR2
Publications for gene TSR2 were updated from 24942156; 20301769 to 20301769; 24942156
Red cell disorders v0.1 STEAP3 Zornitza Stark Added phenotypes hypochromic anaemia for gene: STEAP3
Red cell disorders v0.1 RPS28 Zornitza Stark Added phenotypes 606164 Diamond Blackfan anemia 15 with mandibulofacial dysostosis; Diamond Blackfan anemia 15 with mandibulofacial dysostosis, 606164 for gene: RPS28
Publications for gene RPS28 were updated from 24942156; 20301769 to 20301769; 24942156
Red cell disorders v0.1 RPL18 Zornitza Stark Added phenotypes Diamond-Blackfan anaemia for gene: RPL18
Red cell disorders v0.1 PGK1 Zornitza Stark Added phenotypes 300653 Phosphoglycerate kinase 1 deficiency for gene: PGK1
Publications for gene PGK1 were updated from 6412025; 16740138 to 16740138; 6412025
Red cell disorders v0.1 NHP2 Zornitza Stark Added phenotypes 613987 Dyskeratosis congenita, autosomal recessive 2 for gene: NHP2
Red cell disorders v0.1 NDUFB11 Zornitza Stark Added phenotypes sideroblastic anaemia for gene: NDUFB11
Red cell disorders v0.1 LARS2 Zornitza Stark Added phenotypes hydrops/sideroblastic anaemia for gene: LARS2
Red cell disorders v0.1 YARS2 Zornitza Stark Added phenotypes 613561 Myopathy, lactic acidosis, and sideroblastic anemia 2; Myopathy, lactic acidosis, and sideroblastic anemia 2, 613561 for gene: YARS2
Publications for gene YARS2 were updated from 23918765; 20598274; 22504945 to 23918765; 22504945; 20598274
Red cell disorders v0.1 XK Zornitza Stark Added phenotypes 300842 McLeod syndrome for gene: XK
Publications for gene XK were updated from 11761473; 17683354 to 17683354; 11761473
Red cell disorders v0.1 UMPS Zornitza Stark Added phenotypes 258900 Orotic aciduria with megaloblastic anaemia for gene: UMPS
Red cell disorders v0.1 TRNT1 Zornitza Stark Added phenotypes 616084 Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay; sideroblastic anaemia for gene: TRNT1
Red cell disorders v0.1 TPI1 Zornitza Stark Added phenotypes 615512 Hemolytic anemia due to triosephosphate isomerase deficiency; Enzyme Disorder; Hemolytic anemia due to triosephosphate isomerase deficiency,615512 for gene: TPI1
Publications for gene TPI1 were updated from 9338582; 11698297 to 11698297; 9338582
Red cell disorders v0.1 TMPRSS6 Zornitza Stark Added phenotypes Iron refractoryirondeficiencyanemia,206200; Iron-Refractory Iron Deficiency Anemia; 206200 Iron refractoryirondeficiencyanemia for gene: TMPRSS6
Red cell disorders v0.1 TF Zornitza Stark Added phenotypes Congenital hypotransferrinemia; Atransferrinemia, 209300; 209300 Congenital hypotransferrinemia for gene: TF
Publications for gene TF were updated from 11110675; 1862777; 8187613; 3472216; 10660486 to 8187613; 1862777; 10660486; 3472216; 11110675
Red cell disorders v0.1 TCN2 Zornitza Stark Added phenotypes megaloblastic bone marrow; thrombocytopenia; 275350 Transcobalamin II deficiency; Agammaglobulinemia; pancytopenia; neutropenic colitis; can have a presentation similar to severe combined immunodeficiency; failure to thrive; Transcobalamin II deficiency; neutropenia; hypotonia, myoclonic like movements, pallor, purpura, anaemia, thrombocytopenia, megaloblastosis, aplastic bone marrow for gene: TCN2
Publications for gene TCN2 were updated from 7849710; 10518276 to 10518276; 7849710
Red cell disorders v0.1 SPTB Zornitza Stark Added phenotypes 617948 Elliptocytosis-3; Spherocytosis,616649; Anemia, neonatal hemolytic, fatal and near-fatal; RBC membrane abnormality; 616649 Spherocytosis, type 2; 616649 Anemia, neonatal hemolytic, fatal and near-fatal; Elliptocytosis for gene: SPTB
Red cell disorders v0.1 SPTA1 Zornitza Stark Added phenotypes 270970 Spherocytosis, type 3; RBC membrane abnormality; 266140 Pyropoikilocytosis; Pyropoikilocytosis (BIALLELIC, autosomal or pseudoautosomal), 266140; 266140 Pyropoikilocytosis, 270970 Spherocytosis, type 3; Spherocytosis, type 3 (BIALLELIC, autosomal or pseudoautosomal), 270970; 130600 Elliptocytosis-2; Elliptocytosis-2 (MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown), 130600 for gene: SPTA1
Red cell disorders v0.1 SLC4A1 Zornitza Stark Added phenotypes 166900 Ovalocytosis, SA type, 185020 Cryohydrocytosis; RBC membrane abnormality; 166900 Ovalocytosis, SA type; Haemolytic Anemia; Cryohydrocytosis,185020; 612653 Spherocytosis, type 4; Ovalocytosis, SA type, 166900; Spherocytosis, type 4, 612653 for gene: SLC4A1
Red cell disorders v0.1 SLC2A1 Zornitza Stark Added phenotypes Stomatocytosis; 608885 Stomatin-deficient cryohydrocytosis with neurologic defects; 612126 GLUT1 deficiency without epilepsy and/or hemolytic anemia; Pyridoxine-refractory sideroblastic anemia for gene: SLC2A1
Red cell disorders v0.1 SLC25A38 Zornitza Stark Added phenotypes Anemia, sideroblastic, 2, pyridoxine-refractory, 205950; 205950 Pyridoxine refractory sideroblastic anaemia 2; 205950 Anemia, sideroblastic, 2, pyridoxine-refractory for gene: SLC25A38
Red cell disorders v0.1 SLC19A2 Zornitza Stark Added phenotypes 249270 Thiamine-Responsive Megaloblastic Anemia syndrome; Thiamine-Responsive Megaloblastic Anemia syndrome, 249270; 249270 Thiamine-responsive megaloblastic anemia syndrome for gene: SLC19A2
Red cell disorders v0.1 SLC11A2 Zornitza Stark Added phenotypes 206100 Anemia, hypochromic microcytic, with iron overload 1; Anemia, hypochromic microcytic, with iron overload 1, 206100 for gene: SLC11A2
Publications for gene SLC11A2 were updated from 15459009; 16439678; 16160008 to 16160008; 16439678; 15459009
Red cell disorders v0.1 SEC23B Zornitza Stark Added phenotypes Congenital Dyserythropoietic Anemia; ANEMIA, DYSERYTHROPOIETIC CONGENITAL, TYPE II; 224100 ANEMIA, DYSERYTHROPOIETIC CONGENITAL, TYPE II; Anemia, dyserythropoieticcongenital, type II, 224100; Congenital dyserythropoietic anemia type II; 224100 Congenital dyserythropoietic anaemia type 2 for gene: SEC23B
Red cell disorders v0.1 SBDS Zornitza Stark Added phenotypes 260400 Shwachman-Diamond syndrome; Shwachman-Diamond syndrome for gene: SBDS
Red cell disorders v0.1 RPS7 Zornitza Stark Added phenotypes Inherited Bone Marrow Failure Syndromes; Diamond Blackfan anemia; Diamond-Blackfan anemia 8, 612563; 612563 Diamond_Blackfan Anemia 8; DIAMOND-BLACKFAN ANEMIA 8; Diamond-Blackfan Anemia; 612563 Diamond-Blackfan anemia 8; Diamond_Blackfan Anemia 8 for gene: RPS7
Red cell disorders v0.1 RPS29 Zornitza Stark Added phenotypes Diamond-Blackfan anemia 13, 615909; 615909 Diamond-Blackfan anemia 13 for gene: RPS29
Red cell disorders v0.1 RPS27 Zornitza Stark Added phenotypes Diamond-Blackfan anemia; ?Diamond-Blackfan anemia 17, 617409; 617409 ?Diamond-Blackfan anemia 17, for gene: RPS27
Publications for gene RPS27 were updated from 23718193; 25424902 to 25424902; 23718193
Red cell disorders v0.1 RPS26 Zornitza Stark Added phenotypes Diamond-Blackfan anemia 10, 613309; Inherited Bone Marrow Failure Syndromes; Diamond-Blackfan anemia 10; Diamond Blackfan anemia; Diamond-Blackfan Anemia; 613309 Diamond_Blackfan Anemia 10; Diamond_Blackfan Anemia 10; 613309 Diamond-Blackfan anemia 10 for gene: RPS26
Publications for gene RPS26 were updated from 23812780; 20116044; 24942156 to 24942156; 20116044; 23812780
Red cell disorders v0.1 RPS24 Zornitza Stark Added phenotypes Inherited Bone Marrow Failure Syndromes; Diamond-Blackfan Anemia 3; Diamond-blackfan anemia 3, 610629; Diamond Blackfan anemia; Diamond-Blackfan Anemia; DIAMOND-BLACKFAN ANEMIA 3; Diamond_Blackfan Anemia 3; 610629 Diamond_Blackfan Anemia 3; 610629 Diamond-blackfan anemia 3 for gene: RPS24
Red cell disorders v0.1 RPS19 Zornitza Stark Added phenotypes Inherited Bone Marrow Failure Syndromes; Diamond Blackfan anemia; 105650 Diamond-Blackfan anemia 1; 105650 Diamond_Blackfan Anemia 1; Diamond-Blackfan Anemia; DIAMOND-BLACKFAN ANEMIA 1; Diamond-Blackfan anemia 1, 105650; Diamond_Blackfan Anemia for gene: RPS19
Red cell disorders v0.1 RPS17 Zornitza Stark Added phenotypes Diamond-Blackfan anemia 4, 612527; 612527 Diamond-Blackfan anemia 4 for gene: RPS17
Publications for gene RPS17 were updated from 19953637; 19061985; 17647292; 22045982 to 17647292; 22045982; 19953637; 19061985
Red cell disorders v0.1 RPS10 Zornitza Stark Added phenotypes 613308 Diamond-Blackfan anemia 9; Inherited Bone Marrow Failure Syndromes; Diamond Blackfan anemia; DIAMOND-BLACKFAN ANEMIA 9; Diamond-Blackfan Anemia 9; Diamond-Blackfan Anemia; Diamond-Blackfan anemia 9, 613308; 613308 Diamond_Blackfan Anemia 9; Diamond_Blackfan Anemia 9 for gene: RPS10
Red cell disorders v0.1 RPL9 Zornitza Stark Added phenotypes N/A Diamond-Blackfan anemia; Diamond-Blackfan anemia; ?Diamond-Blackfan anaemia for gene: RPL9
Red cell disorders v0.1 RPL5 Zornitza Stark Added phenotypes Inherited Bone Marrow Failure Syndromes; Diamond Blackfan anemia; 612561 Diamond-Blackfan anemia 6; Diamond-Blackfan anemia 6, 612561; Diamond-Blackfan Anemia 6; 612561 Diamond_Blackfan Anemia 6; Diamond-Blackfan Anemia; DIAMOND-BLACKFAN ANEMIA 6; Diamond_Blackfan Anemia 6 for gene: RPL5
Red cell disorders v0.1 RPL35A Zornitza Stark Added phenotypes Inherited Bone Marrow Failure Syndromes; DIAMOND-BLACKFAN ANEMIA 5; Diamond-Blackfan anemia 5, 612528; 612528 Diamond-Blackfan anemia 5; Diamond Blackfan anemia; Diamond-Blackfan Anemia; Diamond-Blackfan Anemia 5; 612528 Diamond_Blackfan Anemia 5; Diamond_Blackfan Anemia 5 for gene: RPL35A
Red cell disorders v0.1 RPL31 Zornitza Stark Added phenotypes N/A ? Diamond-Blackfan Anaemia for gene: RPL31
Red cell disorders v0.1 RPL27 Zornitza Stark Added phenotypes Diamond-Blackfan anemia; Diamond-Blackfan anemia 16, 617408 for gene: RPL27
Red cell disorders v0.1 RPL26 Zornitza Stark Added phenotypes ?Diamond-Blackfan anemia 11, 614900; 614900 ?Diamond-Blackfan anemia 11 for gene: RPL26
Red cell disorders v0.1 RPL15 Zornitza Stark Added phenotypes 615550 ?Diamond-Blackfan anaemia 12; ?Diamond-Blackfan anemia 12, 615550; 615550 ?Diamond-Blackfan anemia 1 for gene: RPL15
Red cell disorders v0.1 RPL11 Zornitza Stark Added phenotypes Diamond_Blackfan Anemia 7; Inherited Bone Marrow Failure Syndromes; Diamond Blackfan anemia; Diamond-Blackfan Anemia; 612562 Diamond-Blackfan anemia 7; Diamond-Blackfan Anemia 7; 612562 Diamond_Blackfan Anemia 7; DIAMOND-BLACKFAN ANEMIA 7; Diamond-Blackfan anemia 7, 612562 for gene: RPL11
Red cell disorders v0.1 RHAG Zornitza Stark Added phenotypes Stomatocytosis; Anemia, hemolytic, Rh-null, regulator type (BIALLELIC, autosomal or pseudoautosomal), 268150; 185000 Overhydrated hereditary stomatocytosis; Overhydrated hereditary stomatocytosis (MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown), 185000; 268150 Anemia, hemolytic, Rh-null, regulator type for gene: RHAG
Red cell disorders v0.1 PUS1 Zornitza Stark Added phenotypes 600462 Myopathy, lactic acidosis, and sideroblastic anemia 1; Myopathy, Lactic Acidosis, and Sideroblastic Anemia, 600462; 600462 Myopathy, Lactic Acidosis, and Sideroblastic Anemia for gene: PUS1
Red cell disorders v0.1 PKLR Zornitza Stark Added phenotypes Enzyme Disorder; PYRUVATE KINASE DEFICIENCY; 266200 Pyruvate kinase deficiency; Pyruvate kinase deficiency, 266200; 266200 PYRUVATE KINASE DEFICIENCY; Pyruvate kinase deficiency for gene: PKLR
Red cell disorders v0.1 PIEZO1 Zornitza Stark Added phenotypes 194380 Stomatocytosis; Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema, 194380; Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema; Stomatocytosis; Dehydrated hereditary stomatocytosis; 616843 Lymphatic malformation 6; 194380 Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema; Hereditary xerocytosis for gene: PIEZO1
Red cell disorders v0.1 PFKM Zornitza Stark Added phenotypes Glycogen storage disease VII, 232800; 232800 Glycogen storage disease VII for gene: PFKM
Red cell disorders v0.1 NT5C3A Zornitza Stark Added phenotypes Anemia, hemolytic, due to UMPH1 deficiency, 266120; 266120 Anemia, hemolytic, due to UMPH1 deficiency for gene: NT5C3A
Publications for gene NT5C3A were updated from 12714505; 11369620 to 11369620; 12714505
Red cell disorders v0.1 MTRR Zornitza Stark Added phenotypes Homocystinuria-megaloblastic anemia, cbl E type, 236270; 236270 Homocystinuria-megaloblastic anemia, cbl E type for gene: MTRR
Publications for gene MTRR were updated from 15714522; 12555939 to 12555939; 15714522
Red cell disorders v0.1 MTR Zornitza Stark Added phenotypes Homocystinuria-megaloblastic anemia, cblG complementation type, 250940; 250940 Homocystinuria-megaloblastic anemia, cblG complementation type for gene: MTR
Red cell disorders v0.1 LPIN2 Zornitza Stark Added phenotypes Congenital dyserythropoietic anemia; Microcytic anemia; Majeed syndrome, 609628; 609628 Microcytic anemia; CDA; Majeed syndrome; 609628 Majeed syndrome for gene: LPIN2
Publications for gene LPIN2 were updated from 15994876; 17330256 to 17330256; 15994876
Red cell disorders v0.1 KLF1 Zornitza Stark Added phenotypes 613673 Congenital dyserythropoietic anaemia type 4; Congenital Dyserythropoietic Anemia; 613673 Congenital Dyserythropoietic Anemia; Dyserythropoietic anemia, congenital, type IV, 613673; Dyserythropoietic anemia, congenital, type IV for gene: KLF1
Red cell disorders v0.1 KIF23 Zornitza Stark Added phenotypes Enzyme Disorder; Anaemia, dyserythropoietic congenital, type III; Congenital dyserythropoietic anemia (CDA); Congenital dyserythropoietic anemia type III; 605064 Congenital dyserythropoietic anaemia type 3; CDA III for gene: KIF23
Red cell disorders v0.1 KCNN4 Zornitza Stark Added phenotypes Hereditary Xerocytosis; 616689 Dehydrated hereditary stomatocytosis 2 for gene: KCNN4
Red cell disorders v0.1 HSPA9 Zornitza Stark Added phenotypes sideroblastic anaemia; 182170 Sideroblastic anaemia 4; 182170 sideroblastic anaemia type 4; Sideroblastic anaemia type 4, 182170 for gene: HSPA9
Red cell disorders v0.1 HK1 Zornitza Stark Added phenotypes 235700 Enzyme Disorder; Hemolytic anemia due to hexokinase deficiency, 235700; 235700 Hemolytic anemia due to hexokinase deficiency; Hemolytic anemia due to hexokinase deficiency; Enzyme Disorder for gene: HK1
Publications for gene HK1 were updated from 12393545; 7655856 to 7655856; 12393545
Red cell disorders v0.1 HBG2 Zornitza Stark Added phenotypes Cyanosis, transient neonatal, 613977; 141749 Globin Disorder; Globin Disorder; Fetal hemoglobin quantitative trait locus 1; 141749 Hereditary persistance of fetal haemoglobin; Fetal hemoglobin quantitative trait locus 1,141749 for gene: HBG2
Red cell disorders v0.1 HBG1 Zornitza Stark Added phenotypes 141749 Globin Disorder; Globin Disorder; Fetal hemoglobin quantitative trait locus 1; 141749 Hereditary persistance of fetal haemoglobin; Fetal hemoglobin quantitative trait locus 1, 141749 for gene: HBG1
Red cell disorders v0.1 HBD Zornitza Stark Added phenotypes Thalassemia due to Hb Lepore; Thalassemia,delta; Thalassemiadue to HbLepore; 141749 Delta-beta thalassaemia, thalassaemia due to Hb Lepore; Thalassemia, delta for gene: HBD
Red cell disorders v0.1 HBB Zornitza Stark Added phenotypes Sickle cell anemia (BIALLELIC, autosomal or pseudoautosomal),603903; Erythremias, beta-; 603902 Thalassemia-beta, dominant inclusion-body; 613985 Thalassemia, beta; Thalassemias, beta-,(BIALLELIC, autosomal or pseudoautosomal), 613985; 603902 Dominand inclusion body beta thalassaemia; 603903 Sickle cell disease; Hereditary persistence of fetal hemoglobin,(MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown),141749; 141749 Delta-beta thalassaemia; Heinz body anemias, beta- (MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown), 140700; Globin Disorder; Thalassemia-beta, dominant inclusion-body, 603902; Delta-beta thalassemia (MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown), 141749; 613985 Beta thalassaemia; Methemoglobinemias, beta- for gene: HBB
Red cell disorders v0.1 HBA2 Zornitza Stark Added phenotypes Hypochromic microcytic anemia; Hemoglobin H disease, nondeletional, 613978; Globin Disorder; 604131 Alpha thalassaemia; Erythrocytosis; 60413 Thalassemia, alpha; Heinz body anemia,140700; Thalassemia, alpha-, 604131 for gene: HBA2
Red cell disorders v0.1 HBA1 Zornitza Stark Added phenotypes Thalassemias, alpha-, 604131; 604131 Thalassemias, alpha; Erythremias, alpha-; Heinz body anemias, alpha-, 140700; Globin Disorder; 604131 Alpha thalassaemia; Hemoglobin H disease, nondeletional, 613978; Methemoglobinemias, alpha- for gene: HBA1
Red cell disorders v0.1 GSS Zornitza Stark Added phenotypes 231900 Enzyme Disorder; Hemolytic anemia due to glutathione synthetase deficiency, 231900; Enzyme Disorder; 266130 Glutathione synthetase deficiency; Glutathione synthetase deficiency, 266130; Hemolytic anemia due to glutathione synthetase deficiency for gene: GSS
Red cell disorders v0.1 GSR Zornitza Stark Added phenotypes Hemolytic anemia due to glutathione reductase deficiency; Enzyme Disorder; NA Enzyme Disorder for gene: GSR
Red cell disorders v0.1 GPI Zornitza Stark Added phenotypes 613470 Hemolytic anemia, nonspherocytic, due to glucose phosphate isomerase deficiency; Hemolytic anemia, nonspherocytic, due to glucose phosphate isomerase deficiency, 613470 for gene: GPI
Red cell disorders v0.1 GLRX5 Zornitza Stark Added phenotypes 616860 Pyridoxine refractory sideroblastic anaemia 3; Anemia, sideroblastic, pyridoxine-refractory, autosomal recessive, 205950; 205950 Anemia, sideroblastic, pyridoxine-refractory, autosomal recessive for gene: GLRX5
Publications for gene GLRX5 were updated from 25342667; 20364084; 17485548 to 20364084; 25342667; 17485548
Red cell disorders v0.1 GIF Zornitza Stark Added phenotypes 261000 Intrinsic factor deficiency for gene: GIF
Red cell disorders v0.1 GCLC Zornitza Stark Added phenotypes 230450 Glutamate-cysteine ligase deficiency; Hemolytic anemia due to gamma-glutamylcysteine synthetase deficiency, 230450; Enzyme Disorder; Glutamate-cysteine ligase deficiency; 230450 Hemolytic anemia due to gamma-glutamylcysteine synthetase deficiency for gene: GCLC
Red cell disorders v0.1 GATA1 Zornitza Stark Added phenotypes Thrombocytopenia, X-linked, with or without dyserythropoietic anemia 300367; 300367 Thrombocytopenia, X-linked, with or without dyserythropoietic anemia; Myelodysplastic syndrome (MDS), Paediatric; Diamond-Blackfan anaemia; Anemia, X-linked, with/without neutropenia and/or platelet abnormalities 300835; 300835 Thrombocytopenia, X-linked, with or without dyserythropoietic anemia; Diamond Blackfan Anaemia; 300367 Diamond Blackfan Anaemia; Anemia, X-linked, with/without neutropenia and/or platelet abnormalities; Thrombocytopenia, X-linked, with or without dyserythropoietic anemia, 300367 for gene: GATA1
Publications for gene GATA1 were updated from 22706301; 24766296; 30228860 to 30228860; 24766296; 22706301
Red cell disorders v0.1 G6PD Zornitza Stark Added phenotypes 300908 Hemolytic anemia, G6PD deficient (favism); Enzyme Disorder; 300908 Hemolytic anemia due to G6PD deficiency; Hemolytic anemia due to G6PD deficiency, 300908 for gene: G6PD
Red cell disorders v0.1 EPB42 Zornitza Stark Added phenotypes Spherocytosis, type 5, 612690; 612690 Hereditary spherocytosis type 5; RBC membrane abnormality; Hereditary spherocytosis type 5; 612690 Spherocytosis, type 5; EPB42-related hereditary spherocytosis; Minkowski-Chauffard disease; Spherocytosis, Recessive; Elliptocytosis for gene: EPB42
Publications for gene EPB42 were updated from 1558976; 7772513; 12176912 to 12176912; 7772513; 1558976
Red cell disorders v0.1 EPB41 Zornitza Stark Added phenotypes Elliptocytosis-1,611804; RBC membrane abnormality; 611804 Hereditary elliptocytosis; 611804 Elliptocytosis-1; Elliptocytosis; Hereditary elliptocytosis for gene: EPB41
Red cell disorders v0.1 DHFR Zornitza Stark Added phenotypes Megaloblastic anemia due to dihydrofolate reductase deficiency, 613839; 613839 Megaloblastic anemia due to dihydrofolate reductase deficiency for gene: DHFR
Publications for gene DHFR were updated from 21310276; 21310277 to 21310277; 21310276
Red cell disorders v0.1 CYB5R3 Zornitza Stark Added phenotypes Methaemoglobinaemia; 250800 Methemoglobinemia; Methaemoglobinaemia type I and II, 250800; 250800 Methaemoglobinaemia type I and II for gene: CYB5R3
Red cell disorders v0.1 CUBN Zornitza Stark Added phenotypes Megaloblastic anemia-1, Finnish type, 261100; Megaloblastic Anemia; 261100 Megaloblastic anemia-1, Finnish type for gene: CUBN
Red cell disorders v0.1 COX4I2 Zornitza Stark Added phenotypes Exocrine Pancreatic Insufficiency, Dyserythropoietic Anemia, and Calvarial Hyperostosis; Exocrine pancreatic insufficiency, dyserythropoietic anemia, and calvarial hyperostosis, 612714; 612714 Exocrine Pancreatic Insufficiency, Dyserythropoietic Anemia, and Calvarial Hyperostosis; Exocrine Pancreatic Insufficiency, Dyserythropoietic Anemia, andCalvarial Hyperostosis; 612714 Exocrine pancreatic insufficiency, dyserythropoietic anemia, and calvarial hyperostosis; Exocrine pancreatic insufficiency, dyserythropoietic anemia, and calvarial hyperostosis for gene: COX4I2
Red cell disorders v0.1 CDAN1 Zornitza Stark Added phenotypes 224120 Dyserythropoietic anemia, congenital, type Ia; 224120 Congenital dyserythropoietic anaemia type 1a; Dyserythropoietic anemia, congenital, type Ia, 224120 for gene: CDAN1
Red cell disorders v0.1 CD59 Zornitza Stark Added phenotypes Dyskeratosis congenita, X-linked, 305000; 305000 Dyskeratosis congenita, X-linked for gene: CD59
Publications for gene CD59 were updated from 23149847; 1382994; 24382084 to 1382994; 24382084; 23149847
Red cell disorders v0.1 C15orf41 Zornitza Stark Added phenotypes 615631 Congenital dyserythropoietic anaemia type 1b; Congenital Dyserythropoietic Anemia; 615631 Congenital Dyserythropoietic Anemia; Dyserythropoietic anemia, congenital, type Ib, 615631; Dyserythropoietic anemia, congenital, type Ib for gene: C15orf41
Publications for gene C15orf41 were updated from 29885034; 29031773; 23716552 to 29031773; 23716552; 29885034
Red cell disorders v0.1 ANK1 Zornitza Stark Added phenotypes Spherocytosis, type 1; Spherocytosis, type 1,182900; RBC membrane abnormality; 182900 Spherocytosis, type 1; 182900 RBC membrane abnormality for gene: ANK1
Publications for gene ANK1 were updated from 9590147; 7883994; 11167760 to 7883994; 9590147; 11167760
Red cell disorders v0.1 AMN Zornitza Stark Added phenotypes 261100 Megaloblastic anemia-1, Norwegian type; Megaloblastic anemia-1, Norwegian type, 261100 for gene: AMN
Red cell disorders v0.1 ALDOA Zornitza Stark Added phenotypes Enzyme Disorder; 611881 Aldolase A deficiency; Aldolase A deficiency; Glycogen storage disease; 611881 Glycogen storage disease XII; Glycogen storage disease XII, 611881; Glycogen storage disease due to aldolase A deficiency for gene: ALDOA
Publications for gene ALDOA were updated from 7331996; 8598869 to 8598869; 7331996
Red cell disorders v0.1 ALAS2 Zornitza Stark Added phenotypes Anemia, sideroblastic, 1 300751; Anemia, sideroblastic, 1, 300751; 300751 Sideroblastic anaemia 1; 300751 Anemia, sideroblastic, 1 for gene: ALAS2
Red cell disorders v0.1 AK1 Zornitza Stark Added phenotypes 612631 Hemolytic anemia due to adenylate kinase deficiency; Hemolytic anemia due to adenylate kinase deficiency, 612631 for gene: AK1
Red cell disorders v0.1 ADA2 Zornitza Stark Added phenotypes Diamond Blackfan anaemia for gene: ADA2
Red cell disorders v0.1 ABCG8 Zornitza Stark Added phenotypes 210250 sitosterolaemia; sitosterolaemia for gene: ABCG8
Red cell disorders v0.1 ABCG5 Zornitza Stark Added phenotypes 210250 sitosterolaemia; sitosterolaemia for gene: ABCG5
Red cell disorders v0.1 ABCB7 Zornitza Stark Added phenotypes 301310 Sideroblastic anaemia; Anemia, sideroblastic, with ataxia; Anemia, sideroblastic, with ataxia, 301310; 301310 Sideroblastic Anemia and Ataxia; Sideroblastic Anemia and Ataxia for gene: ABCB7
Publications for gene ABCB7 were updated from 11050011; 11843825; 4045952 to 11843825; 4045952; 11050011
Mendeliome v0.4917 TRAPPC9 Elena Savva edited their review of gene: TRAPPC9: Added comment: PMID: 29187737 - multiple intragenic CNVs reported for this gene; Changed publications: PMID: 29187737
Syndromic Retinopathy v0.142 TRNT1 Zornitza Stark Marked gene: TRNT1 as ready
Syndromic Retinopathy v0.142 TRNT1 Zornitza Stark Gene: trnt1 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.142 TRNT1 Zornitza Stark Phenotypes for gene: TRNT1 were changed from Retinitis pigmentosa and erythrocytic microcytosis to Retinitis pigmentosa and erythrocytic microcytosis, MIM# 616959; Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay, MIM# 616084
Syndromic Retinopathy v0.141 TRNT1 Zornitza Stark Publications for gene: TRNT1 were set to
Syndromic Retinopathy v0.140 TRNT1 Zornitza Stark reviewed gene: TRNT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26494905, 28390992, 27389523; Phenotypes: Retinitis pigmentosa and erythrocytic microcytosis, MIM# 616959, Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay, MIM# 616084; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Syndromic Retinopathy v0.140 TREX1 Zornitza Stark Marked gene: TREX1 as ready
Syndromic Retinopathy v0.140 TREX1 Zornitza Stark Gene: trex1 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.140 TREX1 Zornitza Stark Phenotypes for gene: TREX1 were changed from to Vasculopathy, retinal, with cerebral leukodystrophy, MIM# 192315
Syndromic Retinopathy v0.139 TREX1 Zornitza Stark Publications for gene: TREX1 were set to
Syndromic Retinopathy v0.138 TREX1 Zornitza Stark Mode of inheritance for gene: TREX1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Syndromic Retinopathy v0.137 TREX1 Zornitza Stark reviewed gene: TREX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 17660820; Phenotypes: Vasculopathy, retinal, with cerebral leukodystrophy, MIM# 192315; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v0.53 GPC6 Zornitza Stark Marked gene: GPC6 as ready
Skeletal dysplasia v0.53 GPC6 Zornitza Stark Gene: gpc6 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.53 GPC6 Zornitza Stark Phenotypes for gene: GPC6 were changed from Omodysplasia 1 258315 to Omodysplasia 1 MIM#258315
Skeletal dysplasia v0.52 GPC6 Zornitza Stark Publications for gene: GPC6 were set to
Skeletal dysplasia v0.51 GPC6 Zornitza Stark Tag SV/CNV tag was added to gene: GPC6.
Skeletal dysplasia v0.51 GPC6 Zornitza Stark reviewed gene: GPC6: Rating: GREEN; Mode of pathogenicity: None; Publications: 19481194, 32655339; Phenotypes: Omodysplasia 1 MIM#258315; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4917 GPC6 Zornitza Stark Publications for gene: GPC6 were set to 19481194
Differences of Sex Development v0.172 Tiong Tan Panel name changed from Disorders of Sex Differentiation to Differences of Sex Development
Syndromic Retinopathy v0.137 TMEM216 Zornitza Stark Marked gene: TMEM216 as ready
Syndromic Retinopathy v0.137 TMEM216 Zornitza Stark Gene: tmem216 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.137 TMEM216 Zornitza Stark Phenotypes for gene: TMEM216 were changed from to Joubert syndrome 2, MIM# 608091
Syndromic Retinopathy v0.136 TMEM216 Zornitza Stark Publications for gene: TMEM216 were set to
Syndromic Retinopathy v0.135 TMEM216 Zornitza Stark Mode of inheritance for gene: TMEM216 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Syndromic Retinopathy v0.134 TMEM216 Zornitza Stark reviewed gene: TMEM216: Rating: GREEN; Mode of pathogenicity: None; Publications: 32687549, 20512146; Phenotypes: Joubert syndrome 2, MIM# 608091; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4916 GPC6 Elena Savva reviewed gene: GPC6: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 19481194, 32655339; Phenotypes: Omodysplasia 1 MIM#258315; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mackenzie's Mission_Reproductive Carrier Screening v0.25 CD81 Zornitza Stark edited their review of gene: CD81: Changed rating: RED
Brain Channelopathies v0.28 Bryony Thompson Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Mackenzie's Mission_Reproductive Carrier Screening v0.25 CD81 Zornitza Stark Marked gene: CD81 as ready
Mackenzie's Mission_Reproductive Carrier Screening v0.25 CD81 Zornitza Stark Gene: cd81 has been classified as Red List (Low Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.25 CD81 Zornitza Stark Publications for gene: CD81 were set to
Mackenzie's Mission_Reproductive Carrier Screening v0.24 CD81 Zornitza Stark Classified gene: CD81 as Red List (low evidence)
Mackenzie's Mission_Reproductive Carrier Screening v0.24 CD81 Zornitza Stark Gene: cd81 has been classified as Red List (Low Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.23 CD81 Zornitza Stark commented on gene: CD81: Discussed with Edwin Kirk, downgrade to RED for MM panel.
Mackenzie's Mission_Reproductive Carrier Screening v0.23 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
Renal Tubulointerstitial Disease v0.26 Bryony Thompson Panel types changed to Victorian Clinical Genetics Services; KidGen; Royal Melbourne Hospital; Rare Disease
Mackenzie's Mission_Reproductive Carrier Screening v0.23 CD81 Zornitza Stark reviewed gene: CD81: Rating: AMBER; Mode of pathogenicity: None; Publications: 20237408; Phenotypes: Immunodeficiency, common variable, 6, MIM# 613496; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4916 FKBP14 Zornitza Stark Marked gene: FKBP14 as ready
Mendeliome v0.4916 FKBP14 Zornitza Stark Gene: fkbp14 has been classified as Green List (High Evidence).
Mendeliome v0.4916 FKBP14 Zornitza Stark Phenotypes for gene: FKBP14 were changed from to Ehlers-Danlos syndrome, kyphoscoliotic type, 2, MIM# 614557
Mendeliome v0.4915 FKBP14 Zornitza Stark Publications for gene: FKBP14 were set to
Mendeliome v0.4914 FKBP14 Zornitza Stark Mode of inheritance for gene: FKBP14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4913 FKBP14 Zornitza Stark reviewed gene: FKBP14: Rating: GREEN; Mode of pathogenicity: None; Publications: 22265013, 24773188, 27149304, 31132235, 30561154, 28617417; Phenotypes: Ehlers-Danlos syndrome, kyphoscoliotic type, 2, MIM# 614557; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.879 EPG5 Zornitza Stark Marked gene: EPG5 as ready
Genetic Epilepsy v0.879 EPG5 Zornitza Stark Gene: epg5 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.879 EPG5 Zornitza Stark Publications for gene: EPG5 were set to 23222957; 26917586
Genetic Epilepsy v0.878 EPG5 Zornitza Stark Phenotypes for gene: EPG5 were changed from to Vici syndrome, MIM# 242840
Intellectual disability syndromic and non-syndromic v0.3068 EPG5 Zornitza Stark Phenotypes for gene: EPG5 were changed from Vici syndrome, MIM# 242840 to Vici syndrome, MIM# 242840
Genetic Epilepsy v0.878 EPG5 Zornitza Stark Publications for gene: EPG5 were set to
Intellectual disability syndromic and non-syndromic v0.3068 EPG5 Zornitza Stark Marked gene: EPG5 as ready
Intellectual disability syndromic and non-syndromic v0.3068 EPG5 Zornitza Stark Gene: epg5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3068 EPG5 Zornitza Stark Phenotypes for gene: EPG5 were changed from to Vici syndrome, MIM# 242840
Genetic Epilepsy v0.877 EPG5 Zornitza Stark Mode of inheritance for gene: EPG5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.876 EPG5 Zornitza Stark reviewed gene: EPG5: Rating: GREEN; Mode of pathogenicity: None; Publications: 23222957, 26917586; Phenotypes: Vici syndrome, MIM# 242840; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3067 EPG5 Zornitza Stark Publications for gene: EPG5 were set to
Intellectual disability syndromic and non-syndromic v0.3066 EPG5 Zornitza Stark Mode of inheritance for gene: EPG5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3065 EPG5 Zornitza Stark reviewed gene: EPG5: Rating: GREEN; Mode of pathogenicity: None; Publications: 23222957, 26917586; Phenotypes: Vici syndrome, MIM# 242840; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v0.168 EPG5 Zornitza Stark Marked gene: EPG5 as ready
Combined Immunodeficiency v0.168 EPG5 Zornitza Stark Gene: epg5 has been classified as Green List (High Evidence).
Combined Immunodeficiency v0.168 EPG5 Zornitza Stark Phenotypes for gene: EPG5 were changed from to Vici syndrome, MIM# 242840
Combined Immunodeficiency v0.167 EPG5 Zornitza Stark Publications for gene: EPG5 were set to
Combined Immunodeficiency v0.166 EPG5 Zornitza Stark Mode of inheritance for gene: EPG5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v0.165 EPG5 Zornitza Stark reviewed gene: EPG5: Rating: GREEN; Mode of pathogenicity: None; Publications: 23222957, 26917586; Phenotypes: Vici syndrome, MIM# 242840; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cataract v0.236 EPG5 Zornitza Stark Marked gene: EPG5 as ready
Cataract v0.236 EPG5 Zornitza Stark Gene: epg5 has been classified as Green List (High Evidence).
Cataract v0.236 EPG5 Zornitza Stark Classified gene: EPG5 as Green List (high evidence)
Cataract v0.236 EPG5 Zornitza Stark Gene: epg5 has been classified as Green List (High Evidence).
Cataract v0.235 EPG5 Zornitza Stark gene: EPG5 was added
gene: EPG5 was added to Cataract. Sources: Expert Review
Mode of inheritance for gene: EPG5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EPG5 were set to 23222957; 26917586
Phenotypes for gene: EPG5 were set to Vici syndrome, MIM# 242840
Review for gene: EPG5 was set to GREEN
Added comment: Vici syndrome is a rare congenital multisystem disorder characterized by agenesis of the corpus callosum (ACC), cataracts, pigmentary defects, progressive cardiomyopathy, and variable immunodeficiency. Affected individuals also have profound psychomotor retardation and hypotonia due to a myopathy. Well established gene disease association, over 50 families reported.
Sources: Expert Review
Callosome v0.223 EPG5 Zornitza Stark Marked gene: EPG5 as ready
Callosome v0.223 EPG5 Zornitza Stark Gene: epg5 has been classified as Green List (High Evidence).
Callosome v0.223 EPG5 Zornitza Stark Phenotypes for gene: EPG5 were changed from Vici syndrome, MIM# 242840 to Vici syndrome, MIM# 242840
Callosome v0.223 EPG5 Zornitza Stark Phenotypes for gene: EPG5 were changed from to Vici syndrome, MIM# 242840
Callosome v0.222 EPG5 Zornitza Stark Publications for gene: EPG5 were set to
Callosome v0.221 EPG5 Zornitza Stark Mode of inheritance for gene: EPG5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Callosome v0.220 EPG5 Zornitza Stark reviewed gene: EPG5: Rating: GREEN; Mode of pathogenicity: None; Publications: 23222957, 26917586; Phenotypes: Vici syndrome, MIM# 242840; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4913 EPG5 Zornitza Stark Marked gene: EPG5 as ready
Mendeliome v0.4913 EPG5 Zornitza Stark Gene: epg5 has been classified as Green List (High Evidence).
Mendeliome v0.4913 EPG5 Zornitza Stark Phenotypes for gene: EPG5 were changed from to Vici syndrome, MIM# 242840
Mendeliome v0.4912 EPG5 Zornitza Stark Publications for gene: EPG5 were set to
Mendeliome v0.4911 EPG5 Zornitza Stark Mode of inheritance for gene: EPG5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4910 EPG5 Zornitza Stark reviewed gene: EPG5: Rating: GREEN; Mode of pathogenicity: None; Publications: 23222957, 26917586; Phenotypes: Vici syndrome, MIM# 242840, vacuolar myopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4910 LMX1B Zornitza Stark Marked gene: LMX1B as ready
Mendeliome v0.4910 LMX1B Zornitza Stark Gene: lmx1b has been classified as Green List (High Evidence).
Mendeliome v0.4910 LMX1B Zornitza Stark Phenotypes for gene: LMX1B were changed from to Nail-patella syndrome (MIM#161200); LMX1B-related nephropathy
Mendeliome v0.4909 LMX1B Zornitza Stark Publications for gene: LMX1B were set to
Mendeliome v0.4908 LMX1B Zornitza Stark Mode of inheritance for gene: LMX1B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mackenzie's Mission_Reproductive Carrier Screening v0.23 SEMA4A Zornitza Stark reviewed gene: SEMA4A: Rating: AMBER; Mode of pathogenicity: None; Publications: 16199541; Phenotypes: Cone-rod dystrophy 10, 610283, Retinitis pigmentosa 35, 610282; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4907 SEMA4A Zornitza Stark Marked gene: SEMA4A as ready
Mendeliome v0.4907 SEMA4A Zornitza Stark Gene: sema4a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4907 SEMA4A Zornitza Stark Phenotypes for gene: SEMA4A were changed from to Cone-rod dystrophy 10, 610283; Retinitis pigmentosa 35, 610282
Mendeliome v0.4906 SEMA4A Zornitza Stark Publications for gene: SEMA4A were set to
Mendeliome v0.4905 SEMA4A Zornitza Stark Mode of inheritance for gene: SEMA4A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4904 SEMA4A Zornitza Stark Classified gene: SEMA4A as Amber List (moderate evidence)
Mendeliome v0.4904 SEMA4A Zornitza Stark Gene: sema4a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4903 SEMA4A Zornitza Stark reviewed gene: SEMA4A: Rating: AMBER; Mode of pathogenicity: None; Publications: 16199541, 28805479, 23360997, 15277503; Phenotypes: Cone-rod dystrophy 10, 610283, Retinitis pigmentosa 35, 610282; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cone-rod Dystrophy v0.22 SEMA4A Zornitza Stark Marked gene: SEMA4A as ready
Cone-rod Dystrophy v0.22 SEMA4A Zornitza Stark Gene: sema4a has been classified as Amber List (Moderate Evidence).
Cone-rod Dystrophy v0.22 SEMA4A Zornitza Stark Publications for gene: SEMA4A were set to 30679166
Cone-rod Dystrophy v0.21 SEMA4A Zornitza Stark Mode of inheritance for gene: SEMA4A was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Cone-rod Dystrophy v0.20 SEMA4A Zornitza Stark Classified gene: SEMA4A as Amber List (moderate evidence)
Cone-rod Dystrophy v0.20 SEMA4A Zornitza Stark Gene: sema4a has been classified as Amber List (Moderate Evidence).
Cone-rod Dystrophy v0.19 SEMA4A Zornitza Stark reviewed gene: SEMA4A: Rating: AMBER; Mode of pathogenicity: None; Publications: 16199541, 28805479, 23360997, 15277503; Phenotypes: Cone-rod dystrophy 10, 610283, Retinitis pigmentosa 35, 610282; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinitis pigmentosa v0.81 SEMA4A Zornitza Stark Marked gene: SEMA4A as ready
Retinitis pigmentosa v0.81 SEMA4A Zornitza Stark Gene: sema4a has been classified as Amber List (Moderate Evidence).
Retinitis pigmentosa v0.81 SEMA4A Zornitza Stark Mode of inheritance for gene: SEMA4A was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Retinitis pigmentosa v0.80 SEMA4A Zornitza Stark edited their review of gene: SEMA4A: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinitis pigmentosa v0.80 SEMA4A Zornitza Stark changed review comment from: Bi-allelic variants: two families with RP reported in PMID 16199541, none since.

Mono-allelic variants: p.Arg713Gln reported in 4 individuals in PMID 16199541, however note this variant is present in >10,000 heterozygotes in gnomad and 299 homozygotes and did not segregate with disease in PMID 28805479.; to: Bi-allelic variants: two individuals with RP, and two with cone-rod dystrophy reported in PMID 16199541, none since.

Mono-allelic variants: p.Arg713Gln reported in 4 individuals in PMID 16199541, however note this variant is present in >10,000 heterozygotes in gnomad and 299 homozygotes and did not segregate with disease in PMID 28805479.
Retinitis pigmentosa v0.80 SEMA4A Zornitza Stark Publications for gene: SEMA4A were set to
Retinitis pigmentosa v0.79 SEMA4A Zornitza Stark Classified gene: SEMA4A as Amber List (moderate evidence)
Retinitis pigmentosa v0.79 SEMA4A Zornitza Stark Gene: sema4a has been classified as Amber List (Moderate Evidence).
Retinitis pigmentosa v0.78 SEMA4A Zornitza Stark reviewed gene: SEMA4A: Rating: AMBER; Mode of pathogenicity: None; Publications: 16199541, 28805479, 23360997, 15277503; Phenotypes: Retinitis pigmentosa 35, MIM# 610282; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4903 LMX1B Teresa Zhao reviewed gene: LMX1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 27450397; Phenotypes: Nail-patella syndrome (MIM#161200), LMX1B-related nephropathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hypophosphataemia or rickets v0.22 PHEX Zornitza Stark Marked gene: PHEX as ready
Hypophosphataemia or rickets v0.22 PHEX Zornitza Stark Gene: phex has been classified as Green List (High Evidence).
Hypophosphataemia or rickets v0.22 PHEX Zornitza Stark Tag SV/CNV tag was added to gene: PHEX.
Mendeliome v0.4903 JPH2 Zornitza Stark Marked gene: JPH2 as ready
Mendeliome v0.4903 JPH2 Zornitza Stark Gene: jph2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4903 JPH2 Zornitza Stark Phenotypes for gene: JPH2 were changed from to Cardiomyopathy, hypertrophic, MIM#613873; dilated cardiomyopathy
Mendeliome v0.4902 JPH2 Zornitza Stark Publications for gene: JPH2 were set to
Mendeliome v0.4901 JPH2 Zornitza Stark Mode of inheritance for gene: JPH2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4900 JPH2 Zornitza Stark Classified gene: JPH2 as Amber List (moderate evidence)
Mendeliome v0.4900 JPH2 Zornitza Stark Gene: jph2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4899 JPH2 Zornitza Stark reviewed gene: JPH2: Rating: AMBER; Mode of pathogenicity: None; Publications: 30681346, 17509612, 23973696, 26869393, 28393127, 30235249, 31227780; Phenotypes: Cardiomyopathy, hypertrophic, MIM#613873, dilated cardiomyopathy; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v0.21 JPH2 Zornitza Stark Marked gene: JPH2 as ready
Cardiomyopathy_Paediatric v0.21 JPH2 Zornitza Stark Gene: jph2 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v0.21 JPH2 Zornitza Stark Phenotypes for gene: JPH2 were changed from to Cardiomyopathy, hypertrophic, MIM#613873
Cardiomyopathy_Paediatric v0.20 JPH2 Zornitza Stark Publications for gene: JPH2 were set to
Cardiomyopathy_Paediatric v0.19 JPH2 Zornitza Stark Classified gene: JPH2 as Amber List (moderate evidence)
Cardiomyopathy_Paediatric v0.19 JPH2 Zornitza Stark Gene: jph2 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v0.18 JPH2 Zornitza Stark reviewed gene: JPH2: Rating: AMBER; Mode of pathogenicity: None; Publications: 30681346, 17509612, 23973696, 26869393, 28393127, 30235249; Phenotypes: Cardiomyopathy, hypertrophic, MIM#613873; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Syndromic Retinopathy v0.134 RIMS2 Zornitza Stark Marked gene: RIMS2 as ready
Syndromic Retinopathy v0.134 RIMS2 Zornitza Stark Gene: rims2 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.134 RIMS2 Zornitza Stark Classified gene: RIMS2 as Green List (high evidence)
Syndromic Retinopathy v0.134 RIMS2 Zornitza Stark Gene: rims2 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.133 RIMS2 Zornitza Stark gene: RIMS2 was added
gene: RIMS2 was added to Syndromic Retinopathy. Sources: Expert Review
Mode of inheritance for gene: RIMS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RIMS2 were set to 32470375
Phenotypes for gene: RIMS2 were set to Cone-rod synaptic disorder syndrome, congenital nonprogressive, MIM# 618970
Review for gene: RIMS2 was set to GREEN
Added comment: Biallelic LoF variants reported with syndromic congenital cone-rod synaptic disease in 7 individuals from 4 families. Several individuals had autism. One had night blindness.
Sources: Expert Review
Mendeliome v0.4899 RGR Zornitza Stark Tag disputed tag was added to gene: RGR.
Mendeliome v0.4899 RGR Zornitza Stark Marked gene: RGR as ready
Mendeliome v0.4899 RGR Zornitza Stark Gene: rgr has been classified as Red List (Low Evidence).
Mendeliome v0.4899 RGR Zornitza Stark Phenotypes for gene: RGR were changed from to Retinitis pigmentosa 44, MIM# 613769
Mendeliome v0.4898 RGR Zornitza Stark Publications for gene: RGR were set to
Mendeliome v0.4897 RGR Zornitza Stark Mode of inheritance for gene: RGR was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4896 RGR Zornitza Stark Classified gene: RGR as Red List (low evidence)
Mendeliome v0.4896 RGR Zornitza Stark Gene: rgr has been classified as Red List (Low Evidence).
Mendeliome v0.4895 RGR Zornitza Stark reviewed gene: RGR: Rating: RED; Mode of pathogenicity: None; Publications: 10581022, 30347075, 27748892, 27623334; Phenotypes: Retinitis pigmentosa 44, MIM# 613769; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Retinitis pigmentosa v0.78 RGR Zornitza Stark Marked gene: RGR as ready
Retinitis pigmentosa v0.78 RGR Zornitza Stark Gene: rgr has been classified as Red List (Low Evidence).
Retinitis pigmentosa v0.78 RGR Zornitza Stark Publications for gene: RGR were set to
Retinitis pigmentosa v0.77 RGR Zornitza Stark Classified gene: RGR as Red List (low evidence)
Retinitis pigmentosa v0.77 RGR Zornitza Stark Gene: rgr has been classified as Red List (Low Evidence).
Retinitis pigmentosa v0.76 RGR Zornitza Stark Tag disputed tag was added to gene: RGR.
Retinitis pigmentosa v0.76 RGR Zornitza Stark reviewed gene: RGR: Rating: RED; Mode of pathogenicity: None; Publications: 10581022, 30347075, 27748892, 27623334; Phenotypes: Retinitis pigmentosa 44, MIM# 613769; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4895 RDH11 Zornitza Stark Marked gene: RDH11 as ready
Mendeliome v0.4895 RDH11 Zornitza Stark Gene: rdh11 has been classified as Red List (Low Evidence).
Mendeliome v0.4895 RDH11 Zornitza Stark gene: RDH11 was added
gene: RDH11 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: RDH11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RDH11 were set to 24916380; 15634683; 30731079; 18326732
Phenotypes for gene: RDH11 were set to Retinal dystrophy, juvenile cataracts, and short stature syndrome, MIM# 616108
Review for gene: RDH11 was set to RED
Added comment: Single family reported with compound heterozygous LOF variants segregating with disease in three siblings. Some functional data, but note mouse KO did not have eye phenotype.
Sources: Expert list
Syndromic Retinopathy v0.132 RDH11 Zornitza Stark Marked gene: RDH11 as ready
Syndromic Retinopathy v0.132 RDH11 Zornitza Stark Gene: rdh11 has been classified as Red List (Low Evidence).
Syndromic Retinopathy v0.132 RDH11 Zornitza Stark Phenotypes for gene: RDH11 were changed from to Retinal dystrophy, juvenile cataracts, and short stature syndrome, MIM# 616108
Syndromic Retinopathy v0.131 RDH11 Zornitza Stark Publications for gene: RDH11 were set to
Syndromic Retinopathy v0.130 RDH11 Zornitza Stark Mode of inheritance for gene: RDH11 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Syndromic Retinopathy v0.129 RDH11 Zornitza Stark Classified gene: RDH11 as Red List (low evidence)
Syndromic Retinopathy v0.129 RDH11 Zornitza Stark Gene: rdh11 has been classified as Red List (Low Evidence).
Syndromic Retinopathy v0.128 RDH11 Zornitza Stark reviewed gene: RDH11: Rating: RED; Mode of pathogenicity: None; Publications: 24916380, 15634683, 30731079, 18326732; Phenotypes: Retinal dystrophy, juvenile cataracts, and short stature syndrome, MIM# 616108; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4894 CEP112 Zornitza Stark Marked gene: CEP112 as ready
Mendeliome v0.4894 CEP112 Zornitza Stark Gene: cep112 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4894 CEP112 Zornitza Stark Phenotypes for gene: CEP112 were changed from Acephalic spermatozoa; infertility to Spermatogenic failure 44, MIM#619044; Acephalic spermatozoa; infertility
Mendeliome v0.4893 CEP112 Zornitza Stark reviewed gene: CEP112: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Spermatogenic failure 44, MIM#619044; Mode of inheritance: None
Mendeliome v0.4893 SVIL Zornitza Stark Phenotypes for gene: SVIL were changed from myopathy to Myofibrillar myopathy, MIM#619040
Mendeliome v0.4892 SVIL Zornitza Stark edited their review of gene: SVIL: Changed rating: AMBER; Changed phenotypes: Myofibrillar myopathy, MIM#619040
Macular Dystrophy/Stargardt Disease v0.26 PRDM13 Zornitza Stark Publications for gene: PRDM13 were set to 29258872; 28973654; 26507665
Macular Dystrophy/Stargardt Disease v0.25 PRDM13 Zornitza Stark reviewed gene: PRDM13: Rating: GREEN; Mode of pathogenicity: None; Publications: 30710461; Phenotypes: Retinal dystrophy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4892 PRDM13 Zornitza Stark Tag SV/CNV tag was added to gene: PRDM13.
Tag 5'UTR tag was added to gene: PRDM13.
Macular Dystrophy/Stargardt Disease v0.25 PRDM13 Zornitza Stark Marked gene: PRDM13 as ready
Macular Dystrophy/Stargardt Disease v0.25 PRDM13 Zornitza Stark Gene: prdm13 has been classified as Green List (High Evidence).
Macular Dystrophy/Stargardt Disease v0.25 PRDM13 Zornitza Stark Tag 5'UTR tag was added to gene: PRDM13.
Retinitis pigmentosa v0.76 POMGNT1 Zornitza Stark edited their review of gene: POMGNT1: Changed phenotypes: Retinitis pigmentosa 76, MIM#617123
Retinitis pigmentosa v0.76 POMGNT1 Zornitza Stark Marked gene: POMGNT1 as ready
Retinitis pigmentosa v0.76 POMGNT1 Zornitza Stark Gene: pomgnt1 has been classified as Green List (High Evidence).
Retinitis pigmentosa v0.76 POMGNT1 Zornitza Stark Phenotypes for gene: POMGNT1 were changed from Retinitis pigmentosa 76 to Retinitis pigmentosa 76, MIM#617123
Retinitis pigmentosa v0.75 POMGNT1 Zornitza Stark Publications for gene: POMGNT1 were set to
Retinitis pigmentosa v0.74 POMGNT1 Zornitza Stark reviewed gene: POMGNT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27391550, 26908613; Phenotypes: Retinitis pigmentosa; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Syndromic Retinopathy v0.128 PNPLA6 Zornitza Stark edited their review of gene: PNPLA6: Changed publications: 24355708, 25033069
Syndromic Retinopathy v0.128 PNPLA6 Zornitza Stark changed review comment from: Ataxia is part of the phenotype.
Sources: Expert list; to: Choreoretinal dystrophy is part of the phenotype.
Sources: Expert list
Syndromic Retinopathy v0.128 PLK4 Zornitza Stark changed review comment from: Microcephaly and chorioretinopathy, autosomal recessive, 2, MIM# 616171; to: Microcephaly and chorioretinopathy, autosomal recessive, 2, MIM# 616171, three unrelated families reported.
Cone-rod Dystrophy v0.19 PDE6H Zornitza Stark Marked gene: PDE6H as ready
Cone-rod Dystrophy v0.19 PDE6H Zornitza Stark Gene: pde6h has been classified as Red List (Low Evidence).
Cone-rod Dystrophy v0.19 PDE6H Zornitza Stark Phenotypes for gene: PDE6H were changed from Retinal Cone Dystrophy 3, 610024; Achromatopsia 6, 610024 to Retinal Cone Dystrophy 3, 610024
Cone-rod Dystrophy v0.18 PDE6H Zornitza Stark Publications for gene: PDE6H were set to 30679166
Cone-rod Dystrophy v0.17 PDE6H Zornitza Stark Mode of inheritance for gene: PDE6H was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cone-rod Dystrophy v0.16 PDE6H Zornitza Stark Classified gene: PDE6H as Red List (low evidence)
Cone-rod Dystrophy v0.16 PDE6H Zornitza Stark Gene: pde6h has been classified as Red List (Low Evidence).
Cone-rod Dystrophy v0.15 PDE6H Zornitza Stark reviewed gene: PDE6H: Rating: RED; Mode of pathogenicity: None; Publications: 15629837, 22901948; Phenotypes: Retinal cone dystrophy 3, MIM# 610024; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Syndromic Retinopathy v0.128 PAX2 Zornitza Stark Marked gene: PAX2 as ready
Syndromic Retinopathy v0.128 PAX2 Zornitza Stark Gene: pax2 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.128 PAX2 Zornitza Stark Phenotypes for gene: PAX2 were changed from to Papillorenal syndrome, MIM# 120330
Syndromic Retinopathy v0.127 PAX2 Zornitza Stark Mode of inheritance for gene: PAX2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Syndromic Retinopathy v0.126 PAX2 Zornitza Stark reviewed gene: PAX2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Papillorenal syndrome, MIM# 120330; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Vitreoretinopathy v0.10 P3H2 Zornitza Stark Marked gene: P3H2 as ready
Vitreoretinopathy v0.10 P3H2 Zornitza Stark Gene: p3h2 has been classified as Green List (High Evidence).
Mendeliome v0.4892 GPC6 Zornitza Stark Marked gene: GPC6 as ready
Mendeliome v0.4892 GPC6 Zornitza Stark Gene: gpc6 has been classified as Green List (High Evidence).
Mendeliome v0.4892 GPC6 Zornitza Stark Tag SV/CNV tag was added to gene: GPC6.
Mendeliome v0.4892 GPC6 Zornitza Stark Phenotypes for gene: GPC6 were changed from to Omodysplasia 1 (MIM#258315), AR
Mendeliome v0.4891 GPC6 Zornitza Stark Publications for gene: GPC6 were set to
Mendeliome v0.4890 GPC6 Zornitza Stark Mode of inheritance for gene: GPC6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4889 GPC6 Kristin Rigbye reviewed gene: GPC6: Rating: GREEN; Mode of pathogenicity: None; Publications: 19481194; Phenotypes: Omodysplasia 1 (MIM#258315), AR; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Syndromic Retinopathy v0.126 TINF2 Zornitza Stark Marked gene: TINF2 as ready
Syndromic Retinopathy v0.126 TINF2 Zornitza Stark Gene: tinf2 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.126 TINF2 Zornitza Stark Classified gene: TINF2 as Green List (high evidence)
Syndromic Retinopathy v0.126 TINF2 Zornitza Stark Gene: tinf2 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.125 TINF2 Zornitza Stark gene: TINF2 was added
gene: TINF2 was added to Syndromic Retinopathy. Sources: Expert list
Mode of inheritance for gene: TINF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TINF2 were set to 18252230; 21477109; 28095086; 28866069; 29749240; 30478948
Phenotypes for gene: TINF2 were set to Revesz syndrome, 268130
Review for gene: TINF2 was set to GREEN
Added comment: Bilateral exudative retinopathy is a defining feature of Revesz syndrome, in addition to other manifestations such as bone marrow failure, intracranial calcification and cerebellar hypoplasia. Multiple (>3) unrelated cases reported in literature with retinal findings.
Sources: Expert list
Retinitis pigmentosa v0.74 SPATA7 Zornitza Stark Marked gene: SPATA7 as ready
Retinitis pigmentosa v0.74 SPATA7 Zornitza Stark Gene: spata7 has been classified as Green List (High Evidence).
Retinitis pigmentosa v0.74 SPATA7 Zornitza Stark Publications for gene: SPATA7 were set to
Retinitis pigmentosa v0.73 SPATA7 Zornitza Stark reviewed gene: SPATA7: Rating: GREEN; Mode of pathogenicity: None; Publications: 31908400, 32799588; Phenotypes: Leber congenital amaurosis 3, MIM#604232, Autosomal recessive juvenile retinitis pigmentosa, MIM#604232; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4889 SPATA7 Zornitza Stark Marked gene: SPATA7 as ready
Mendeliome v0.4889 SPATA7 Zornitza Stark Gene: spata7 has been classified as Green List (High Evidence).
Mendeliome v0.4889 SPATA7 Zornitza Stark Phenotypes for gene: SPATA7 were changed from to Leber congenital amaurosis 3, MIM#604232; Autosomal recessive juvenile retinitis pigmentosa, MIM#604232
Mendeliome v0.4888 SPATA7 Zornitza Stark Publications for gene: SPATA7 were set to
Mendeliome v0.4887 SPATA7 Zornitza Stark Mode of inheritance for gene: SPATA7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4886 SPATA7 Chern Lim reviewed gene: SPATA7: Rating: GREEN; Mode of pathogenicity: None; Publications: 31908400, 32799588; Phenotypes: Leber congenital amaurosis 3, MIM#604232, Autosomal recessive juvenile retinitis pigmentosa, MIM#604232; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Renal Ciliopathies and Nephronophthisis v0.118 PKHD1 Zornitza Stark Marked gene: PKHD1 as ready
Renal Ciliopathies and Nephronophthisis v0.118 PKHD1 Zornitza Stark Gene: pkhd1 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v0.118 PKHD1 Zornitza Stark Classified gene: PKHD1 as Green List (high evidence)
Renal Ciliopathies and Nephronophthisis v0.118 PKHD1 Zornitza Stark Gene: pkhd1 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v0.117 PKHD1 Zornitza Stark gene: PKHD1 was added
gene: PKHD1 was added to Renal Ciliopathies and Nephronophthisis. Sources: Expert Review
Mode of inheritance for gene: PKHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PKHD1 were set to Polycystic kidney disease 4, with or without hepatic disease, MIM# 263200
Review for gene: PKHD1 was set to GREEN
Added comment: Included due to possible phenotypic overlap.
Sources: Expert Review
Mendeliome v0.4886 KIRREL3 Zornitza Stark Marked gene: KIRREL3 as ready
Mendeliome v0.4886 KIRREL3 Zornitza Stark Gene: kirrel3 has been classified as Red List (Low Evidence).
Mendeliome v0.4886 KIRREL3 Zornitza Stark gene: KIRREL3 was added
gene: KIRREL3 was added to Mendeliome. Sources: Expert list
refuted tags were added to gene: KIRREL3.
Mode of inheritance for gene: KIRREL3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIRREL3 were set to 19012874
Phenotypes for gene: KIRREL3 were set to Intellectual disability
Review for gene: KIRREL3 was set to RED
Added comment: Variants associated with ID have now been re-classified based on population frequency.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.3065 KIRREL3 Zornitza Stark Tag refuted tag was added to gene: KIRREL3.
Mendeliome v0.4885 NEUROD1 Zornitza Stark Marked gene: NEUROD1 as ready
Mendeliome v0.4885 NEUROD1 Zornitza Stark Gene: neurod1 has been classified as Green List (High Evidence).
Mendeliome v0.4885 NEUROD1 Zornitza Stark Phenotypes for gene: NEUROD1 were changed from to Maturity-onset diabetes of the young 6, MIM#606394; Retinitis pigmentosa, retinopathy, permanent neonatal diabetes
Mendeliome v0.4884 NEUROD1 Zornitza Stark Publications for gene: NEUROD1 were set to
Mendeliome v0.4883 NEUROD1 Zornitza Stark Mode of inheritance for gene: NEUROD1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4882 NEUROD1 Zornitza Stark reviewed gene: NEUROD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25477324, 25684977, 22784109, 29521454; Phenotypes: Maturity-onset diabetes of the young 6, MIM#606394, Retinitis pigmentosa, retinopathy, permanent neonatal diabetes; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Retinitis pigmentosa v0.73 NEUROD1 Zornitza Stark Marked gene: NEUROD1 as ready
Retinitis pigmentosa v0.73 NEUROD1 Zornitza Stark Gene: neurod1 has been classified as Green List (High Evidence).
Retinitis pigmentosa v0.73 NEUROD1 Zornitza Stark Phenotypes for gene: NEUROD1 were changed from ?retinitis pigmentosa; neonatal diabetes, systematic neurological abnormalities, and early-onset retinal dystrophy to Retinitis pigmentosa; Retinopathy; Permanent neonatal diabetes
Retinitis pigmentosa v0.72 NEUROD1 Zornitza Stark changed review comment from: Mono-allelic variants in this gene are associated with MODY.

Rare reports of bi-allelic variants, sometimes with permanent neonatal diabetes, but RP/retinopathy reported in three unrelated individuals.; to: Mono-allelic variants in this gene are associated with MODY.

Rare reports of bi-allelic variants, sometimes with permanent neonatal diabetes, but RP/retinopathy reported in three unrelated individuals. Functional data to support gene's role in retina.
Retinitis pigmentosa v0.72 NEUROD1 Zornitza Stark edited their review of gene: NEUROD1: Changed rating: GREEN
Retinitis pigmentosa v0.72 NEUROD1 Zornitza Stark reviewed gene: NEUROD1: Rating: ; Mode of pathogenicity: None; Publications: 25477324, 25684977, 22784109, 29521454; Phenotypes: Retinitis pigmentosa, Retinopathy, Permanent neonatal diabetes; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Syndromic Retinopathy v0.124 MTTP Zornitza Stark Marked gene: MTTP as ready
Syndromic Retinopathy v0.124 MTTP Zornitza Stark Gene: mttp has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.124 MTTP Zornitza Stark Phenotypes for gene: MTTP were changed from to Abetalipoproteinemia, MIM# 200100
Syndromic Retinopathy v0.123 MTTP Zornitza Stark Mode of inheritance for gene: MTTP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Syndromic Retinopathy v0.122 MTTP Zornitza Stark reviewed gene: MTTP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Abetalipoproteinemia, MIM# 200100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Syndromic Retinopathy v0.122 MFN2 Zornitza Stark Marked gene: MFN2 as ready
Syndromic Retinopathy v0.122 MFN2 Zornitza Stark Gene: mfn2 has been classified as Amber List (Moderate Evidence).
Syndromic Retinopathy v0.122 MFN2 Zornitza Stark Phenotypes for gene: MFN2 were changed from to Charcot-Marie-Tooth disease, axonal, type 2A2A, MIM# 609260; Charcot-Marie-Tooth disease, axonal, type 2A2B, MIM# 617087
Syndromic Retinopathy v0.121 MFN2 Zornitza Stark Publications for gene: MFN2 were set to
Syndromic Retinopathy v0.120 MFN2 Zornitza Stark Mode of inheritance for gene: MFN2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Syndromic Retinopathy v0.119 MFN2 Zornitza Stark Classified gene: MFN2 as Amber List (moderate evidence)
Syndromic Retinopathy v0.119 MFN2 Zornitza Stark Gene: mfn2 has been classified as Amber List (Moderate Evidence).
Syndromic Retinopathy v0.118 MFN2 Zornitza Stark reviewed gene: MFN2: Rating: AMBER; Mode of pathogenicity: None; Publications: 30922813, 28487236, 21707411, 22957060; Phenotypes: Charcot-Marie-Tooth disease, axonal, type 2A2A, MIM# 609260, Charcot-Marie-Tooth disease, axonal, type 2A2B, MIM# 617087; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Syndromic Retinopathy v0.118 LAMA1 Zornitza Stark Marked gene: LAMA1 as ready
Syndromic Retinopathy v0.118 LAMA1 Zornitza Stark Gene: lama1 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.118 LAMA1 Zornitza Stark Phenotypes for gene: LAMA1 were changed from to Poretti-Boltshauser syndrome, MIM# 615960
Syndromic Retinopathy v0.117 LAMA1 Zornitza Stark Mode of inheritance for gene: LAMA1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Syndromic Retinopathy v0.116 LAMA1 Zornitza Stark reviewed gene: LAMA1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Poretti-Boltshauser syndrome, MIM# 615960; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Syndromic Retinopathy v0.116 INVS Zornitza Stark Marked gene: INVS as ready
Syndromic Retinopathy v0.116 INVS Zornitza Stark Gene: invs has been classified as Amber List (Moderate Evidence).
Syndromic Retinopathy v0.116 INVS Zornitza Stark Phenotypes for gene: INVS were changed from Nephronophthisis 2, infantile to Nephronophthisis 2, infantile, MIM#602088
Syndromic Retinopathy v0.115 INVS Zornitza Stark Publications for gene: INVS were set to
Syndromic Retinopathy v0.114 INVS Zornitza Stark Classified gene: INVS as Amber List (moderate evidence)
Syndromic Retinopathy v0.114 INVS Zornitza Stark Gene: invs has been classified as Amber List (Moderate Evidence).
Syndromic Retinopathy v0.113 INVS Zornitza Stark reviewed gene: INVS: Rating: AMBER; Mode of pathogenicity: None; Publications: 16522655; Phenotypes: Nephronophthisis 2, infantile, MIM# 602088; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Syndromic Retinopathy v0.113 IKBKG Zornitza Stark Marked gene: IKBKG as ready
Syndromic Retinopathy v0.113 IKBKG Zornitza Stark Gene: ikbkg has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.113 IKBKG Zornitza Stark Classified gene: IKBKG as Green List (high evidence)
Syndromic Retinopathy v0.113 IKBKG Zornitza Stark Gene: ikbkg has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.112 IKBKG Zornitza Stark gene: IKBKG was added
gene: IKBKG was added to Syndromic Retinopathy. Sources: Expert list
Mode of inheritance for gene: IKBKG was set to Other
Phenotypes for gene: IKBKG were set to Incontinentia pigmenti, MIM# 308300
Review for gene: IKBKG was set to GREEN
Added comment: Well established gene-disease association. Eye involvement is variable, but retinal abnormalities are common including retinal vascular proliferation, retinal ischaemia, retinal bleeding, retinal fibrosis, retinal detachment, foveal hypoplasia, foveal disorganisation.
Sources: Expert list
Syndromic Retinopathy v0.111 IFT81 Zornitza Stark Marked gene: IFT81 as ready
Syndromic Retinopathy v0.111 IFT81 Zornitza Stark Gene: ift81 has been classified as Amber List (Moderate Evidence).
Syndromic Retinopathy v0.111 IFT81 Zornitza Stark Phenotypes for gene: IFT81 were changed from to Short-rib thoracic dysplasia 19 with or without polydactyly, MIM# 617895
Syndromic Retinopathy v0.110 IFT81 Zornitza Stark Publications for gene: IFT81 were set to
Syndromic Retinopathy v0.109 IFT81 Zornitza Stark Mode of inheritance for gene: IFT81 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Syndromic Retinopathy v0.108 IFT81 Zornitza Stark Classified gene: IFT81 as Amber List (moderate evidence)
Syndromic Retinopathy v0.108 IFT81 Zornitza Stark Gene: ift81 has been classified as Amber List (Moderate Evidence).
Syndromic Retinopathy v0.107 IFT81 Zornitza Stark changed review comment from: Gene has been predominantly associated with severe short-rib thoracic dysplasia with no retinopathy reported. Isolated retinopathy reported in one individual, PMID 28460050, and an NCL-like phenotype in another in PMID 26275418. Overall, good evidence this is a ciliopathy gene, but moderate evidence of retinal phenotype.; to: Gene has been predominantly associated with severe short-rib thoracic dysplasia with no retinopathy reported. Isolated retinopathy reported in one individual, PMID 28460050, and an NCL-like phenotype in another in PMID 26275418. Overall, good evidence this is a ciliopathy gene, but moderate evidence for retinal phenotype.
Syndromic Retinopathy v0.107 IFT81 Zornitza Stark reviewed gene: IFT81: Rating: AMBER; Mode of pathogenicity: None; Publications: 28460050, 26275418, 27666822, 32783357; Phenotypes: Short-rib thoracic dysplasia 19 with or without polydactyly, MIM# 617895; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinitis pigmentosa v0.71 IFT172 Zornitza Stark Marked gene: IFT172 as ready
Retinitis pigmentosa v0.71 IFT172 Zornitza Stark Gene: ift172 has been classified as Green List (High Evidence).
Retinitis pigmentosa v0.71 IFT172 Zornitza Stark Phenotypes for gene: IFT172 were changed from Retinitis pigmentosa 71 to Retinitis pigmentosa 71, MIM#616394
Retinitis pigmentosa v0.70 IFT172 Zornitza Stark Publications for gene: IFT172 were set to
Retinitis pigmentosa v0.69 IFT172 Zornitza Stark reviewed gene: IFT172: Rating: GREEN; Mode of pathogenicity: None; Publications: 25168386, 29659833; Phenotypes: Retinitis pigmentosa 71, MIM# 616394; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Foveal Hypoplasia v0.5 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Congenital Stationary Night Blindness v0.7 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Retinal Disorders Superpanel v1.80 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Cone-rod Dystrophy v0.14 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Mendeliome v0.4882 DNAAF4 Zornitza Stark Tag SV/CNV tag was added to gene: DNAAF4.
Tag founder tag was added to gene: DNAAF4.
Mendeliome v0.4882 DNAAF4 Zornitza Stark Marked gene: DNAAF4 as ready
Mendeliome v0.4882 DNAAF4 Zornitza Stark Gene: dnaaf4 has been classified as Green List (High Evidence).
Mendeliome v0.4882 DNAAF4 Zornitza Stark Phenotypes for gene: DNAAF4 were changed from to Ciliary dyskinesia, primary, 25, MIM# 615482
Mendeliome v0.4881 DNAAF4 Zornitza Stark Publications for gene: DNAAF4 were set to
Mendeliome v0.4880 DNAAF4 Zornitza Stark Mode of inheritance for gene: DNAAF4 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4880 DNAAF4 Zornitza Stark Mode of inheritance for gene: DNAAF4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4879 DNAAF4 Zornitza Stark reviewed gene: DNAAF4: Rating: GREEN; Mode of pathogenicity: None; Publications: 23872636; Phenotypes: Ciliary dyskinesia, primary, 25, MIM# 615482; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.134 DNAAF4 Zornitza Stark Tag SV/CNV tag was added to gene: DNAAF4.
Tag founder tag was added to gene: DNAAF4.
Heterotaxy v0.112 DNAAF4 Zornitza Stark Marked gene: DNAAF4 as ready
Heterotaxy v0.112 DNAAF4 Zornitza Stark Gene: dnaaf4 has been classified as Green List (High Evidence).
Heterotaxy v0.112 DNAAF4 Zornitza Stark Tag SV/CNV tag was added to gene: DNAAF4.
Tag founder tag was added to gene: DNAAF4.
Heterotaxy v0.112 DNAAF4 Zornitza Stark Phenotypes for gene: DNAAF4 were changed from to Ciliary dyskinesia, primary, 25, MIM# 615482
Heterotaxy v0.111 DNAAF4 Zornitza Stark Publications for gene: DNAAF4 were set to
Heterotaxy v0.110 DNAAF4 Zornitza Stark Mode of inheritance for gene: DNAAF4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.109 DNAAF4 Zornitza Stark reviewed gene: DNAAF4: Rating: GREEN; Mode of pathogenicity: None; Publications: 23872636; Phenotypes: Ciliary dyskinesia, primary, 25, MIM# 615482; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.134 DNAAF4 Zornitza Stark Publications for gene: DNAAF4 were set to
Ciliary Dyskinesia v0.133 DNAAF4 Zornitza Stark changed review comment from: Note there is a common 3.5kb affecting exon 7, possible founder effect.; to: Well established gene-disease association, multiple families and animal model. Note there is a common 3.5kb affecting exon 7, possible founder effect.
Ciliary Dyskinesia v0.133 DNAAF4 Zornitza Stark edited their review of gene: DNAAF4: Changed publications: 23872636
Ciliary Dyskinesia v0.133 DNAAF4 Zornitza Stark Marked gene: DNAAF4 as ready
Ciliary Dyskinesia v0.133 DNAAF4 Zornitza Stark Gene: dnaaf4 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.133 DNAAF4 Zornitza Stark Phenotypes for gene: DNAAF4 were changed from to Ciliary dyskinesia, primary, 25, MIM# 615482
Ciliary Dyskinesia v0.132 DNAAF4 Zornitza Stark Mode of inheritance for gene: DNAAF4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.131 DNAAF4 Zornitza Stark reviewed gene: DNAAF4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 25, MIM# 615482; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4879 MAG Zornitza Stark Phenotypes for gene: MAG were changed from Spastic paraplegia 75, autosomal recessive, MIM# 616680 to Spastic paraplegia 75, autosomal recessive, MIM# 616680; Cerebellar ataxia
Mendeliome v0.4878 MAG Zornitza Stark changed review comment from: Spastic paraplegia-75 is an autosomal recessive, slowly progressive neurodegenerative disorder characterized by onset of spastic paraplegia and cognitive impairment in childhood. Eight unrelated families reported.; to: Spastic paraplegia-75 is an autosomal recessive, slowly progressive neurodegenerative disorder characterized by onset of spastic paraplegia and cognitive impairment in childhood. Eight unrelated families reported with variable combinations of psychomotor delay, ataxia, eye movement abnormalities, spasticity, dystonia, and neuropathic symptoms.
Hereditary Spastic Paraplegia v0.155 MAG Zornitza Stark Deleted their comment
Hereditary Spastic Paraplegia v0.155 MAG Zornitza Stark changed review comment from: Spastic paraplegia-75 is an autosomal recessive, slowly progressive neurodegenerative disorder characterized by onset of spastic paraplegia and cognitive impairment in childhood. Eight unrelated families reported.; to: Spastic paraplegia-75 is an autosomal recessive, slowly progressive neurodegenerative disorder characterized by onset of spastic paraplegia and cognitive impairment in childhood. Eight unrelated families reported with variable combinations of psychomotor delay, ataxia, eye movement abnormalities, spasticity, dystonia, and neuropathic symptoms.
Hereditary Spastic Paraplegia v0.155 MAG Zornitza Stark Phenotypes for gene: MAG were changed from Spastic paraplegia 75, autosomal recessive, 616680 to Spastic paraplegia 75, autosomal recessive, 616680; Cerebellar ataxia
Hereditary Spastic Paraplegia v0.154 MAG Zornitza Stark edited their review of gene: MAG: Changed phenotypes: Spastic paraplegia 75, autosomal recessive, MIM# 616680, Cerebellar ataxia
Hereditary Spastic Paraplegia v0.154 MAG Zornitza Stark edited their review of gene: MAG: Added comment: Four more individuals reported with variable combinations of psychomotor delay, ataxia, eye movement abnormalities, spasticity, dystonia, and neuropathic symptoms.; Changed publications: 24482476, 26179919, 31402626, 32629324, 32629324
Ataxia v0.263 MAG Zornitza Stark Publications for gene: MAG were set to 32629324; 32340215
Ataxia v0.262 MAG Zornitza Stark edited their review of gene: MAG: Added comment: Four more individuals reported with variable combinations of psychomotor delay, ataxia, eye movement abnormalities, spasticity, dystonia, and neuropathic symptoms.; Changed publications: 32629324, 32340215, 32629324; Changed phenotypes: Spastic paraplegia 75, autosomal recessive, MIM# 616680, Cerebellar ataxia, Oculomotor apraxia
Intellectual disability syndromic and non-syndromic v0.3065 HK1 Zornitza Stark Phenotypes for gene: HK1 were changed from to Neurodevelopmental disorder with visual defects and brain anomalies, MIM# 618547
Intellectual disability syndromic and non-syndromic v0.3064 HK1 Zornitza Stark reviewed gene: HK1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with visual defects and brain anomalies, MIM# 618547; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Syndromic Retinopathy v0.106 HCCS Zornitza Stark Marked gene: HCCS as ready
Syndromic Retinopathy v0.106 HCCS Zornitza Stark Gene: hccs has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.106 HCCS Zornitza Stark Classified gene: HCCS as Green List (high evidence)
Syndromic Retinopathy v0.106 HCCS Zornitza Stark Gene: hccs has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.105 HCCS Zornitza Stark gene: HCCS was added
gene: HCCS was added to Syndromic Retinopathy. Sources: Expert list
Mode of inheritance for gene: HCCS was set to Other
Phenotypes for gene: HCCS were set to Linear skin defects with multiple congenital anomalies 1, MIM# 309801
Review for gene: HCCS was set to GREEN
Added comment: Complex disorder typically associated with microphthalmia and structural eye abnormalities, however pigmentary retinopathy also reported.
Sources: Expert list
Mendeliome v0.4878 GZF1 Zornitza Stark Marked gene: GZF1 as ready
Mendeliome v0.4878 GZF1 Zornitza Stark Gene: gzf1 has been classified as Green List (High Evidence).
Mendeliome v0.4878 GZF1 Zornitza Stark Phenotypes for gene: GZF1 were changed from to Joint laxity, short stature, and myopia, MIM# 617662; Larsen-like syndrome
Mendeliome v0.4877 GZF1 Zornitza Stark Publications for gene: GZF1 were set to
Mendeliome v0.4876 GZF1 Zornitza Stark Mode of inheritance for gene: GZF1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4875 GZF1 Zornitza Stark reviewed gene: GZF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33009817, 28475863; Phenotypes: Joint laxity, short stature, and myopia, MIM# 617662, Larsen-like syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v0.51 GZF1 Zornitza Stark Phenotypes for gene: GZF1 were changed from Larsen syndrome to Joint laxity, short stature, and myopia, MIM# 617662; Larsen-like syndrome
Skeletal dysplasia v0.50 GZF1 Zornitza Stark Publications for gene: GZF1 were set to 28475863
Skeletal dysplasia v0.49 GZF1 Zornitza Stark Classified gene: GZF1 as Green List (high evidence)
Skeletal dysplasia v0.49 GZF1 Zornitza Stark Gene: gzf1 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.48 GZF1 Zornitza Stark reviewed gene: GZF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33009817, 28475863; Phenotypes: Joint laxity, short stature, and myopia, MIM# 617662; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Stickler Syndrome v0.6 GZF1 Zornitza Stark Marked gene: GZF1 as ready
Stickler Syndrome v0.6 GZF1 Zornitza Stark Gene: gzf1 has been classified as Green List (High Evidence).
Stickler Syndrome v0.6 GZF1 Zornitza Stark Phenotypes for gene: GZF1 were changed from to Joint laxity, short stature, and myopia, MIM# 617662
Stickler Syndrome v0.5 GZF1 Zornitza Stark Publications for gene: GZF1 were set to
Stickler Syndrome v0.4 GZF1 Zornitza Stark Mode of inheritance for gene: GZF1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Stickler Syndrome v0.3 GZF1 Zornitza Stark reviewed gene: GZF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33009817, 28475863; Phenotypes: Joint laxity, short stature, and myopia, MIM# 617662; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Syndromic Retinopathy v0.104 GRN Zornitza Stark changed review comment from: Bi-allelic variants cause CLN, retinal degeneration prominent. However, also reports of retinal abnormalities with mono-allelic variants, which are typically associated with a frontotemporal dementia phenotype.; to: Bi-allelic variants cause CLN, retinal degeneration prominent. However, also limited reports of retinal abnormalities with mono-allelic variants, which are typically associated with a frontotemporal dementia phenotype.
Syndromic Retinopathy v0.104 GRN Zornitza Stark Publications for gene: GRN were set to
Syndromic Retinopathy v0.103 GRN Zornitza Stark edited their review of gene: GRN: Added comment: Bi-allelic variants cause CLN, retinal degeneration prominent. However, also reports of retinal abnormalities with mono-allelic variants, which are typically associated with a frontotemporal dementia phenotype.; Changed publications: 31855245, 28404863, 30922528
Congenital Stationary Night Blindness v0.6 GNB3 Zornitza Stark Phenotypes for gene: GNB3 were changed from Night blindness, congenital stationary, type 1h to Night blindness, congenital stationary, type 1H, MIM# 617024
Congenital Stationary Night Blindness v0.5 GNB3 Zornitza Stark Marked gene: GNB3 as ready
Congenital Stationary Night Blindness v0.5 GNB3 Zornitza Stark Gene: gnb3 has been classified as Green List (High Evidence).
Congenital Stationary Night Blindness v0.5 GNB3 Zornitza Stark Publications for gene: GNB3 were set to
Congenital Stationary Night Blindness v0.4 GNB3 Zornitza Stark reviewed gene: GNB3: Rating: GREEN; Mode of pathogenicity: None; Publications: 27063057, 17065478; Phenotypes: Night blindness, congenital stationary, type 1H, MIM# 617024; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4875 ITFG2 Zornitza Stark Marked gene: ITFG2 as ready
Mendeliome v0.4875 ITFG2 Zornitza Stark Gene: itfg2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4875 ITFG2 Zornitza Stark Classified gene: ITFG2 as Amber List (moderate evidence)
Mendeliome v0.4875 ITFG2 Zornitza Stark Gene: itfg2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4874 ITFG2 Zornitza Stark gene: ITFG2 was added
gene: ITFG2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ITFG2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ITFG2 were set to 28397838; https://doi.org/10.1038/s41525-020-00150-z
Phenotypes for gene: ITFG2 were set to Neurodevelopmental abnormality; Intellectual disability; Developmental regression; Ataxia
Review for gene: ITFG2 was set to AMBER
Added comment: ITFG2 was suggested to be a candidate gene for autosomal recessive ID in the study by Harripaul et al (2018 - PMID: 28397838). The authors performed microarray and exome sequencing in 192 consanguineous families and identified a homozygous ITGF2 stopgain variant (NM_018463.3:c.472G>T / p.Glu158*) along with 3 additional variants segregating with ID within an investigated family (PK51). Cheema et al (2020 - https://doi.org/10.1038/s41525-020-00150-z) report briefly on a male, born to consanguineous parents presenting with NDD, seizures, regression and ataxia. There was a similarly affected female sibling. Evaluation of ROH revealed a homozygous ITFG2 nonsense variant [NM_018463.3:c.361C>T / p.(Gln121*)]. Families in this study were investigated by trio WES or WGS. Evaluation of data of the same lab revealed 3 additional unrelated subjects with overlapping phenotypes, notably NDD and ataxia. These individuals were - each - homozygous for pLoF variants [NM_018463.3:c.848-1G>A; NM_018463.3:c.704dupC, p.(Ala236fs), NM_018463.3:c.1000_1001delAT, p.(Ile334fs)]. As discussed in OMIM, ITFG2 encodes a subunit of the KICSTOR protein complex, having a role in regulating nutrient sensing by MTOR complex-1 (Wolfson et al 2017 - PMID : 28199306).

Rated Amber as Cheema et al report on diagnostic outcomes and multiple candidate genes as part of a heterogenous cohort and details are therefore limited.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3064 ITFG2 Zornitza Stark Marked gene: ITFG2 as ready
Intellectual disability syndromic and non-syndromic v0.3064 ITFG2 Zornitza Stark Added comment: Comment when marking as ready: Agree with Amber rating, considering reported as part of heterogenous cohort reporting diagnostic outcomes and multiple candidate genes.
Intellectual disability syndromic and non-syndromic v0.3064 ITFG2 Zornitza Stark Gene: itfg2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3064 ITFG2 Zornitza Stark Classified gene: ITFG2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3064 ITFG2 Zornitza Stark Gene: itfg2 has been classified as Amber List (Moderate Evidence).
Polymicrogyria and Schizencephaly v0.155 Zornitza Stark Panel types changed to Australian Genomics; Victorian Clinical Genetics Services; Rare Disease
Callosome v0.220 SHMT2 Zornitza Stark Marked gene: SHMT2 as ready
Callosome v0.220 SHMT2 Zornitza Stark Gene: shmt2 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.154 SHMT2 Zornitza Stark Marked gene: SHMT2 as ready
Polymicrogyria and Schizencephaly v0.154 SHMT2 Zornitza Stark Gene: shmt2 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.154 SHMT2 Zornitza Stark Classified gene: SHMT2 as Green List (high evidence)
Polymicrogyria and Schizencephaly v0.154 SHMT2 Zornitza Stark Gene: shmt2 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.153 SHMT2 Zornitza Stark gene: SHMT2 was added
gene: SHMT2 was added to Polymicrogyria and Schizencephaly. Sources: Literature
Mode of inheritance for gene: SHMT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SHMT2 were set to 33015733
Phenotypes for gene: SHMT2 were set to Congenital microcephaly; Infantile axial hypotonia; Spastic paraparesis; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum; Abnormal cortical gyration; Hypertrophic cardiomyopathy; Abnormality of the face; Proximal placement of thumb; 2-3 toe syndactyly
Review for gene: SHMT2 was set to GREEN
Added comment: García‑Cazorla et al. (2020 - PMID: 33015733) report 5 individuals (from 4 families) with a novel brain and heart developmental syndrome caused by biallelic SHMT2 pathogenic variants.

All affected subjects presented similar phenotype incl. microcephaly at birth (5/5 with OFC < -2 SD though in 2/5 cases N OFC was observed later), DD and ID (1/5 mild-moderate, 1/5 moderate, 3/5 severe), motor dysfunction in the form of spastic (5/5) paraparesis, ataxia/dysmetria (3/4), intention tremor (in 3/?) and/or peripheral neuropathy (2 sibs). They exhibited corpus callosum hypoplasia (5/5) and perisylvian microgyria-like pattern (4/5). Cardiac problems were reported in all, with hypertrophic cardiomyopathy in 4/5 (from 3 families) and atrial-SD in the 5th individual (1/5). Common dysmorphic features incl. long palpebral/fissures, eversion of lateral third of lower eylids, arched eyebrows, long eyelashes, thin upper lip, short Vth finger, fetal pads, mild 2-3 toe syndactyly, proximally placed thumbs.

Biallelic variants were identified following exome sequencing in all (other investigations not mentioned). Identified variants were in all cases missense SNVs or in-frame del, which together with evidence from population databases and mouse model might suggest a hypomorphic effect of variants and intolerance/embryonic lethality for homozygous LoF ones.

SHMT2 encodes the mitohondrial form of serine hydroxymethyltransferase. The enzyme transfers one-carbon units from serine to tetrahydrofolate (THF) and generates glycine and 5,10,methylene-THF.

Mitochondrial defect was suggested by presence of ragged red fibers in myocardial biopsy of one patient. Quadriceps and myocardial biopsies of the same individual were overall suggestive of myopathic changes.

While plasma metabolites were within N range and SHMT2 protein levels not significantly altered in patient fibroblasts, the authors provide evidence for impaired enzymatic function eg. presence of the SHMT2 substrate (THF) in patient but not control (mitochondria-enriched) fibroblasts , decrease in glycine/serine ratios, impared folate metabolism. Patient fibroblasts displayed impaired oxidative capacity (reduced ATP levels in a medium without glucose, diminished oxygen consumption rates). Mitochondrial membrane potential and ROS levels were also suggestive of redox malfunction.

Shmt2 ko in mice was previously shown to be embryonically lethal attributed to severe mitochondrial respiration defects, although there was no observed brain metabolic defect.

The authors performed Shmt2 knockdown in motoneurons in Drosophila, demonstrating neuromuscular junction (# of satellite boutons) and motility defects (climbing distance/velocity).
Sources: Literature
Callosome v0.220 SHMT2 Zornitza Stark Classified gene: SHMT2 as Green List (high evidence)
Callosome v0.220 SHMT2 Zornitza Stark Gene: shmt2 has been classified as Green List (High Evidence).
Callosome v0.219 SHMT2 Zornitza Stark gene: SHMT2 was added
gene: SHMT2 was added to Callosome. Sources: Literature
Mode of inheritance for gene: SHMT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SHMT2 were set to 33015733
Phenotypes for gene: SHMT2 were set to Congenital microcephaly; Infantile axial hypotonia; Spastic paraparesis; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum; Abnormal cortical gyration; Hypertrophic cardiomyopathy; Abnormality of the face; Proximal placement of thumb; 2-3 toe syndactyly
Review for gene: SHMT2 was set to GREEN
Added comment: García‑Cazorla et al. (2020 - PMID: 33015733) report 5 individuals (from 4 families) with a novel brain and heart developmental syndrome caused by biallelic SHMT2 pathogenic variants.

All affected subjects presented similar phenotype incl. microcephaly at birth (5/5 with OFC < -2 SD though in 2/5 cases N OFC was observed later), DD and ID (1/5 mild-moderate, 1/5 moderate, 3/5 severe), motor dysfunction in the form of spastic (5/5) paraparesis, ataxia/dysmetria (3/4), intention tremor (in 3/?) and/or peripheral neuropathy (2 sibs). They exhibited corpus callosum hypoplasia (5/5) and perisylvian microgyria-like pattern (4/5). Cardiac problems were reported in all, with hypertrophic cardiomyopathy in 4/5 (from 3 families) and atrial-SD in the 5th individual (1/5). Common dysmorphic features incl. long palpebral/fissures, eversion of lateral third of lower eylids, arched eyebrows, long eyelashes, thin upper lip, short Vth finger, fetal pads, mild 2-3 toe syndactyly, proximally placed thumbs.

Biallelic variants were identified following exome sequencing in all (other investigations not mentioned). Identified variants were in all cases missense SNVs or in-frame del, which together with evidence from population databases and mouse model might suggest a hypomorphic effect of variants and intolerance/embryonic lethality for homozygous LoF ones.

SHMT2 encodes the mitohondrial form of serine hydroxymethyltransferase. The enzyme transfers one-carbon units from serine to tetrahydrofolate (THF) and generates glycine and 5,10,methylene-THF.

Mitochondrial defect was suggested by presence of ragged red fibers in myocardial biopsy of one patient. Quadriceps and myocardial biopsies of the same individual were overall suggestive of myopathic changes.

While plasma metabolites were within N range and SHMT2 protein levels not significantly altered in patient fibroblasts, the authors provide evidence for impaired enzymatic function eg. presence of the SHMT2 substrate (THF) in patient but not control (mitochondria-enriched) fibroblasts , decrease in glycine/serine ratios, impared folate metabolism. Patient fibroblasts displayed impaired oxidative capacity (reduced ATP levels in a medium without glucose, diminished oxygen consumption rates). Mitochondrial membrane potential and ROS levels were also suggestive of redox malfunction.

Shmt2 ko in mice was previously shown to be embryonically lethal attributed to severe mitochondrial respiration defects, although there was no observed brain metabolic defect.

The authors performed Shmt2 knockdown in motoneurons in Drosophila, demonstrating neuromuscular junction (# of satellite boutons) and motility defects (climbing distance/velocity).
Sources: Literature
Mitochondrial disease v0.510 SHMT2 Zornitza Stark Marked gene: SHMT2 as ready
Mitochondrial disease v0.510 SHMT2 Zornitza Stark Gene: shmt2 has been classified as Green List (High Evidence).
Mitochondrial disease v0.510 SHMT2 Zornitza Stark Classified gene: SHMT2 as Green List (high evidence)
Mitochondrial disease v0.510 SHMT2 Zornitza Stark Gene: shmt2 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v0.154 SHMT2 Zornitza Stark Marked gene: SHMT2 as ready
Hereditary Spastic Paraplegia v0.154 SHMT2 Zornitza Stark Gene: shmt2 has been classified as Green List (High Evidence).
Mitochondrial disease v0.509 SHMT2 Zornitza Stark gene: SHMT2 was added
gene: SHMT2 was added to Mitochondrial disease. Sources: Literature
Mode of inheritance for gene: SHMT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SHMT2 were set to 33015733
Phenotypes for gene: SHMT2 were set to Congenital microcephaly; Infantile axial hypotonia; Spastic paraparesis; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum; Abnormal cortical gyration; Hypertrophic cardiomyopathy; Abnormality of the face; Proximal placement of thumb; 2-3 toe syndactyly
Review for gene: SHMT2 was set to GREEN
Added comment: García‑Cazorla et al. (2020 - PMID: 33015733) report 5 individuals (from 4 families) with a novel brain and heart developmental syndrome caused by biallelic SHMT2 pathogenic variants.

All affected subjects presented similar phenotype incl. microcephaly at birth (5/5 with OFC < -2 SD though in 2/5 cases N OFC was observed later), DD and ID (1/5 mild-moderate, 1/5 moderate, 3/5 severe), motor dysfunction in the form of spastic (5/5) paraparesis, ataxia/dysmetria (3/4), intention tremor (in 3/?) and/or peripheral neuropathy (2 sibs). They exhibited corpus callosum hypoplasia (5/5) and perisylvian microgyria-like pattern (4/5). Cardiac problems were reported in all, with hypertrophic cardiomyopathy in 4/5 (from 3 families) and atrial-SD in the 5th individual (1/5). Common dysmorphic features incl. long palpebral/fissures, eversion of lateral third of lower eylids, arched eyebrows, long eyelashes, thin upper lip, short Vth finger, fetal pads, mild 2-3 toe syndactyly, proximally placed thumbs.

Biallelic variants were identified following exome sequencing in all (other investigations not mentioned). Identified variants were in all cases missense SNVs or in-frame del, which together with evidence from population databases and mouse model might suggest a hypomorphic effect of variants and intolerance/embryonic lethality for homozygous LoF ones.

SHMT2 encodes the mitohondrial form of serine hydroxymethyltransferase. The enzyme transfers one-carbon units from serine to tetrahydrofolate (THF) and generates glycine and 5,10,methylene-THF.

Mitochondrial defect was suggested by presence of ragged red fibers in myocardial biopsy of one patient. Quadriceps and myocardial biopsies of the same individual were overall suggestive of myopathic changes.

While plasma metabolites were within N range and SHMT2 protein levels not significantly altered in patient fibroblasts, the authors provide evidence for impaired enzymatic function eg. presence of the SHMT2 substrate (THF) in patient but not control (mitochondria-enriched) fibroblasts , decrease in glycine/serine ratios, impared folate metabolism. Patient fibroblasts displayed impaired oxidative capacity (reduced ATP levels in a medium without glucose, diminished oxygen consumption rates). Mitochondrial membrane potential and ROS levels were also suggestive of redox malfunction.

Shmt2 ko in mice was previously shown to be embryonically lethal attributed to severe mitochondrial respiration defects, although there was no observed brain metabolic defect.

The authors performed Shmt2 knockdown in motoneurons in Drosophila, demonstrating neuromuscular junction (# of satellite boutons) and motility defects (climbing distance/velocity).
Sources: Literature
Hereditary Spastic Paraplegia v0.154 SHMT2 Zornitza Stark Classified gene: SHMT2 as Green List (high evidence)
Hereditary Spastic Paraplegia v0.154 SHMT2 Zornitza Stark Gene: shmt2 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v0.153 SHMT2 Zornitza Stark gene: SHMT2 was added
gene: SHMT2 was added to Hereditary Spastic Paraplegia - paediatric. Sources: Literature
Mode of inheritance for gene: SHMT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SHMT2 were set to 33015733
Phenotypes for gene: SHMT2 were set to Congenital microcephaly; Infantile axial hypotonia; Spastic paraparesis; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum; Abnormal cortical gyration; Hypertrophic cardiomyopathy; Abnormality of the face; Proximal placement of thumb; 2-3 toe syndactyly
Review for gene: SHMT2 was set to GREEN
Added comment: García‑Cazorla et al. (2020 - PMID: 33015733) report 5 individuals (from 4 families) with a novel brain and heart developmental syndrome caused by biallelic SHMT2 pathogenic variants.

All affected subjects presented similar phenotype incl. microcephaly at birth (5/5 with OFC < -2 SD though in 2/5 cases N OFC was observed later), DD and ID (1/5 mild-moderate, 1/5 moderate, 3/5 severe), motor dysfunction in the form of spastic (5/5) paraparesis, ataxia/dysmetria (3/4), intention tremor (in 3/?) and/or peripheral neuropathy (2 sibs). They exhibited corpus callosum hypoplasia (5/5) and perisylvian microgyria-like pattern (4/5). Cardiac problems were reported in all, with hypertrophic cardiomyopathy in 4/5 (from 3 families) and atrial-SD in the 5th individual (1/5). Common dysmorphic features incl. long palpebral/fissures, eversion of lateral third of lower eylids, arched eyebrows, long eyelashes, thin upper lip, short Vth finger, fetal pads, mild 2-3 toe syndactyly, proximally placed thumbs.

Biallelic variants were identified following exome sequencing in all (other investigations not mentioned). Identified variants were in all cases missense SNVs or in-frame del, which together with evidence from population databases and mouse model might suggest a hypomorphic effect of variants and intolerance/embryonic lethality for homozygous LoF ones.

SHMT2 encodes the mitohondrial form of serine hydroxymethyltransferase. The enzyme transfers one-carbon units from serine to tetrahydrofolate (THF) and generates glycine and 5,10,methylene-THF.

Mitochondrial defect was suggested by presence of ragged red fibers in myocardial biopsy of one patient. Quadriceps and myocardial biopsies of the same individual were overall suggestive of myopathic changes.

While plasma metabolites were within N range and SHMT2 protein levels not significantly altered in patient fibroblasts, the authors provide evidence for impaired enzymatic function eg. presence of the SHMT2 substrate (THF) in patient but not control (mitochondria-enriched) fibroblasts , decrease in glycine/serine ratios, impared folate metabolism. Patient fibroblasts displayed impaired oxidative capacity (reduced ATP levels in a medium without glucose, diminished oxygen consumption rates). Mitochondrial membrane potential and ROS levels were also suggestive of redox malfunction.

Shmt2 ko in mice was previously shown to be embryonically lethal attributed to severe mitochondrial respiration defects, although there was no observed brain metabolic defect.

The authors performed Shmt2 knockdown in motoneurons in Drosophila, demonstrating neuromuscular junction (# of satellite boutons) and motility defects (climbing distance/velocity).
Sources: Literature
Cardiomyopathy_Paediatric v0.18 SHMT2 Zornitza Stark Marked gene: SHMT2 as ready
Cardiomyopathy_Paediatric v0.18 SHMT2 Zornitza Stark Gene: shmt2 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.18 SHMT2 Zornitza Stark Classified gene: SHMT2 as Green List (high evidence)
Cardiomyopathy_Paediatric v0.18 SHMT2 Zornitza Stark Gene: shmt2 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.17 SHMT2 Zornitza Stark gene: SHMT2 was added
gene: SHMT2 was added to Cardiomyopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: SHMT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SHMT2 were set to 33015733
Phenotypes for gene: SHMT2 were set to Congenital microcephaly; Infantile axial hypotonia; Spastic paraparesis; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum; Abnormal cortical gyration; Hypertrophic cardiomyopathy; Abnormality of the face; Proximal placement of thumb; 2-3 toe syndactyly
Review for gene: SHMT2 was set to GREEN
Added comment: García‑Cazorla et al. (2020 - PMID: 33015733) report 5 individuals (from 4 families) with a novel brain and heart developmental syndrome caused by biallelic SHMT2 pathogenic variants.

All affected subjects presented similar phenotype incl. microcephaly at birth (5/5 with OFC < -2 SD though in 2/5 cases N OFC was observed later), DD and ID (1/5 mild-moderate, 1/5 moderate, 3/5 severe), motor dysfunction in the form of spastic (5/5) paraparesis, ataxia/dysmetria (3/4), intention tremor (in 3/?) and/or peripheral neuropathy (2 sibs). They exhibited corpus callosum hypoplasia (5/5) and perisylvian microgyria-like pattern (4/5). Cardiac problems were reported in all, with hypertrophic cardiomyopathy in 4/5 (from 3 families) and atrial-SD in the 5th individual (1/5). Common dysmorphic features incl. long palpebral/fissures, eversion of lateral third of lower eylids, arched eyebrows, long eyelashes, thin upper lip, short Vth finger, fetal pads, mild 2-3 toe syndactyly, proximally placed thumbs.

Biallelic variants were identified following exome sequencing in all (other investigations not mentioned). Identified variants were in all cases missense SNVs or in-frame del, which together with evidence from population databases and mouse model might suggest a hypomorphic effect of variants and intolerance/embryonic lethality for homozygous LoF ones.

SHMT2 encodes the mitohondrial form of serine hydroxymethyltransferase. The enzyme transfers one-carbon units from serine to tetrahydrofolate (THF) and generates glycine and 5,10,methylene-THF.

Mitochondrial defect was suggested by presence of ragged red fibers in myocardial biopsy of one patient. Quadriceps and myocardial biopsies of the same individual were overall suggestive of myopathic changes.

While plasma metabolites were within N range and SHMT2 protein levels not significantly altered in patient fibroblasts, the authors provide evidence for impaired enzymatic function eg. presence of the SHMT2 substrate (THF) in patient but not control (mitochondria-enriched) fibroblasts , decrease in glycine/serine ratios, impared folate metabolism. Patient fibroblasts displayed impaired oxidative capacity (reduced ATP levels in a medium without glucose, diminished oxygen consumption rates). Mitochondrial membrane potential and ROS levels were also suggestive of redox malfunction.

Shmt2 ko in mice was previously shown to be embryonically lethal attributed to severe mitochondrial respiration defects, although there was no observed brain metabolic defect.

The authors performed Shmt2 knockdown in motoneurons in Drosophila, demonstrating neuromuscular junction (# of satellite boutons) and motility defects (climbing distance/velocity).
Sources: Literature
Microcephaly v0.488 SHMT2 Zornitza Stark Marked gene: SHMT2 as ready
Microcephaly v0.488 SHMT2 Zornitza Stark Gene: shmt2 has been classified as Green List (High Evidence).
Microcephaly v0.488 SHMT2 Zornitza Stark Classified gene: SHMT2 as Green List (high evidence)
Microcephaly v0.488 SHMT2 Zornitza Stark Gene: shmt2 has been classified as Green List (High Evidence).
Microcephaly v0.487 SHMT2 Zornitza Stark gene: SHMT2 was added
gene: SHMT2 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: SHMT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SHMT2 were set to 33015733
Phenotypes for gene: SHMT2 were set to Congenital microcephaly; Infantile axial hypotonia; Spastic paraparesis; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum; Abnormal cortical gyration; Hypertrophic cardiomyopathy; Abnormality of the face; Proximal placement of thumb; 2-3 toe syndactyly
Review for gene: SHMT2 was set to GREEN
Added comment: García‑Cazorla et al. (2020 - PMID: 33015733) report 5 individuals (from 4 families) with a novel brain and heart developmental syndrome caused by biallelic SHMT2 pathogenic variants.

All affected subjects presented similar phenotype incl. microcephaly at birth (5/5 with OFC < -2 SD though in 2/5 cases N OFC was observed later), DD and ID (1/5 mild-moderate, 1/5 moderate, 3/5 severe), motor dysfunction in the form of spastic (5/5) paraparesis, ataxia/dysmetria (3/4), intention tremor (in 3/?) and/or peripheral neuropathy (2 sibs). They exhibited corpus callosum hypoplasia (5/5) and perisylvian microgyria-like pattern (4/5). Cardiac problems were reported in all, with hypertrophic cardiomyopathy in 4/5 (from 3 families) and atrial-SD in the 5th individual (1/5). Common dysmorphic features incl. long palpebral/fissures, eversion of lateral third of lower eylids, arched eyebrows, long eyelashes, thin upper lip, short Vth finger, fetal pads, mild 2-3 toe syndactyly, proximally placed thumbs.

Biallelic variants were identified following exome sequencing in all (other investigations not mentioned). Identified variants were in all cases missense SNVs or in-frame del, which together with evidence from population databases and mouse model might suggest a hypomorphic effect of variants and intolerance/embryonic lethality for homozygous LoF ones.

SHMT2 encodes the mitohondrial form of serine hydroxymethyltransferase. The enzyme transfers one-carbon units from serine to tetrahydrofolate (THF) and generates glycine and 5,10,methylene-THF.

Mitochondrial defect was suggested by presence of ragged red fibers in myocardial biopsy of one patient. Quadriceps and myocardial biopsies of the same individual were overall suggestive of myopathic changes.

While plasma metabolites were within N range and SHMT2 protein levels not significantly altered in patient fibroblasts, the authors provide evidence for impaired enzymatic function eg. presence of the SHMT2 substrate (THF) in patient but not control (mitochondria-enriched) fibroblasts , decrease in glycine/serine ratios, impared folate metabolism. Patient fibroblasts displayed impaired oxidative capacity (reduced ATP levels in a medium without glucose, diminished oxygen consumption rates). Mitochondrial membrane potential and ROS levels were also suggestive of redox malfunction.

Shmt2 ko in mice was previously shown to be embryonically lethal attributed to severe mitochondrial respiration defects, although there was no observed brain metabolic defect.

The authors performed Shmt2 knockdown in motoneurons in Drosophila, demonstrating neuromuscular junction (# of satellite boutons) and motility defects (climbing distance/velocity).
Sources: Literature
Mendeliome v0.4873 SHMT2 Zornitza Stark Marked gene: SHMT2 as ready
Mendeliome v0.4873 SHMT2 Zornitza Stark Gene: shmt2 has been classified as Green List (High Evidence).
Mendeliome v0.4873 SHMT2 Zornitza Stark Classified gene: SHMT2 as Green List (high evidence)
Mendeliome v0.4873 SHMT2 Zornitza Stark Gene: shmt2 has been classified as Green List (High Evidence).
Mendeliome v0.4872 SHMT2 Zornitza Stark gene: SHMT2 was added
gene: SHMT2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SHMT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SHMT2 were set to 33015733
Phenotypes for gene: SHMT2 were set to Congenital microcephaly; Infantile axial hypotonia; Spastic paraparesis; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum; Abnormal cortical gyration; Hypertrophic cardiomyopathy; Abnormality of the face; Proximal placement of thumb; 2-3 toe syndactyly
Review for gene: SHMT2 was set to GREEN
Added comment: García‑Cazorla et al. (2020 - PMID: 33015733) report 5 individuals (from 4 families) with a novel brain and heart developmental syndrome caused by biallelic SHMT2 pathogenic variants.

All affected subjects presented similar phenotype incl. microcephaly at birth (5/5 with OFC < -2 SD though in 2/5 cases N OFC was observed later), DD and ID (1/5 mild-moderate, 1/5 moderate, 3/5 severe), motor dysfunction in the form of spastic (5/5) paraparesis, ataxia/dysmetria (3/4), intention tremor (in 3/?) and/or peripheral neuropathy (2 sibs). They exhibited corpus callosum hypoplasia (5/5) and perisylvian microgyria-like pattern (4/5). Cardiac problems were reported in all, with hypertrophic cardiomyopathy in 4/5 (from 3 families) and atrial-SD in the 5th individual (1/5). Common dysmorphic features incl. long palpebral/fissures, eversion of lateral third of lower eylids, arched eyebrows, long eyelashes, thin upper lip, short Vth finger, fetal pads, mild 2-3 toe syndactyly, proximally placed thumbs.

Biallelic variants were identified following exome sequencing in all (other investigations not mentioned). Identified variants were in all cases missense SNVs or in-frame del, which together with evidence from population databases and mouse model might suggest a hypomorphic effect of variants and intolerance/embryonic lethality for homozygous LoF ones.

SHMT2 encodes the mitohondrial form of serine hydroxymethyltransferase. The enzyme transfers one-carbon units from serine to tetrahydrofolate (THF) and generates glycine and 5,10,methylene-THF.

Mitochondrial defect was suggested by presence of ragged red fibers in myocardial biopsy of one patient. Quadriceps and myocardial biopsies of the same individual were overall suggestive of myopathic changes.

While plasma metabolites were within N range and SHMT2 protein levels not significantly altered in patient fibroblasts, the authors provide evidence for impaired enzymatic function eg. presence of the SHMT2 substrate (THF) in patient but not control (mitochondria-enriched) fibroblasts , decrease in glycine/serine ratios, impared folate metabolism. Patient fibroblasts displayed impaired oxidative capacity (reduced ATP levels in a medium without glucose, diminished oxygen consumption rates). Mitochondrial membrane potential and ROS levels were also suggestive of redox malfunction.

Shmt2 ko in mice was previously shown to be embryonically lethal attributed to severe mitochondrial respiration defects, although there was no observed brain metabolic defect.

The authors performed Shmt2 knockdown in motoneurons in Drosophila, demonstrating neuromuscular junction (# of satellite boutons) and motility defects (climbing distance/velocity).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3063 SHMT2 Zornitza Stark Marked gene: SHMT2 as ready
Intellectual disability syndromic and non-syndromic v0.3063 SHMT2 Zornitza Stark Gene: shmt2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3063 SHMT2 Zornitza Stark Classified gene: SHMT2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3063 SHMT2 Zornitza Stark Gene: shmt2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3062 ITFG2 Konstantinos Varvagiannis gene: ITFG2 was added
gene: ITFG2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ITFG2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ITFG2 were set to 28397838; https://doi.org/10.1038/s41525-020-00150-z
Phenotypes for gene: ITFG2 were set to Neurodevelopmental abnormality; Intellectual disability; Developmental regression; Ataxia
Penetrance for gene: ITFG2 were set to Complete
Review for gene: ITFG2 was set to AMBER
Added comment: ITFG2 was suggested to be a candidate gene for autosomal recessive ID in the study by Harripaul et al (2018 - PMID: 28397838). The authors performed microarray and exome sequencing in 192 consanguineous families and identified a homozygous ITGF2 stopgain variant (NM_018463.3:c.472G>T / p.Glu158*) along with 3 additional variants segregating with ID within an investigated family (PK51).

Cheema et al (2020 - https://doi.org/10.1038/s41525-020-00150-z) report briefly on a male, born to consanguineous parents presenting with NDD, seizures, regression and ataxia. There was a similarly affected female sibling. Evaluation of ROH revealed a homozygous ITFG2 nonsense variant [NM_018463.3:c.361C>T / p.(Gln121*)]. Families in this study were investigated by trio WES or WGS.

Evaluation of data of the same lab revealed 3 additional unrelated subjects with overlapping phenotypes, notably NDD and ataxia. These individuals were - each - homozygous for pLoF variants [NM_018463.3:c.848-1G>A; NM_018463.3:c.704dupC, p.(Ala236fs), NM_018463.3:c.1000_1001delAT, p.(Ile334fs)].

As discussed in OMIM, ITFG2 encodes a subunit of the KICSTOR protein complex, having a role in regulating nutrient sensing by MTOR complex-1 (Wolfson et al 2017 - PMID : 28199306).

Please consider inclusion in the ID panel with amber rating, pending further details.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3062 SHMT2 Konstantinos Varvagiannis gene: SHMT2 was added
gene: SHMT2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SHMT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SHMT2 were set to 33015733
Phenotypes for gene: SHMT2 were set to Congenital microcephaly; Infantile axial hypotonia; Spastic paraparesis; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum; Abnormal cortical gyration; Hypertrophic cardiomyopathy; Abnormality of the face; Proximal placement of thumb; 2-3 toe syndactyly
Penetrance for gene: SHMT2 were set to Complete
Review for gene: SHMT2 was set to GREEN
Added comment: García‑Cazorla et al. (2020 - PMID: 33015733) report 5 individuals (from 4 families) with a novel brain and heart developmental syndrome caused by biallelic SHMT2 pathogenic variants.

All affected subjects presented similar phenotype incl. microcephaly at birth (5/5 with OFC < -2 SD though in 2/5 cases N OFC was observed later), DD and ID (1/5 mild-moderate, 1/5 moderate, 3/5 severe), motor dysfunction in the form of spastic (5/5) paraparesis, ataxia/dysmetria (3/4), intention tremor (in 3/?) and/or peripheral neuropathy (2 sibs). They exhibited corpus callosum hypoplasia (5/5) and perisylvian microgyria-like pattern (4/5). Cardiac problems were reported in all, with hypertrophic cardiomyopathy in 4/5 (from 3 families) and atrial-SD in the 5th individual (1/5). Common dysmorphic features incl. long palpebral/fissures, eversion of lateral third of lower eylids, arched eyebrows, long eyelashes, thin upper lip, short Vth finger, fetal pads, mild 2-3 toe syndactyly, proximally placed thumbs.

Biallelic variants were identified following exome sequencing in all (other investigations not mentioned). Identified variants were in all cases missense SNVs or in-frame del, which together with evidence from population databases and mouse model might suggest a hypomorphic effect of variants and intolerance/embryonic lethality for homozygous LoF ones.

SHMT2 encodes the mitohondrial form of serine hydroxymethyltransferase. The enzyme transfers one-carbon units from serine to tetrahydrofolate (THF) and generates glycine and 5,10,methylene-THF.

Mitochondrial defect was suggested by presence of ragged red fibers in myocardial biopsy of one patient. Quadriceps and myocardial biopsies of the same individual were overall suggestive of myopathic changes.

While plasma metabolites were within N range and SHMT2 protein levels not significantly altered in patient fibroblasts, the authors provide evidence for impaired enzymatic function eg. presence of the SHMT2 substrate (THF) in patient but not control (mitochondria-enriched) fibroblasts , decrease in glycine/serine ratios, impared folate metabolism. Patient fibroblasts displayed impaired oxidative capacity (reduced ATP levels in a medium without glucose, diminished oxygen consumption rates). Mitochondrial membrane potential and ROS levels were also suggestive of redox malfunction.

Shmt2 ko in mice was previously shown to be embryonically lethal attributed to severe mitochondrial respiration defects, although there was no observed brain metabolic defect.

The authors performed Shmt2 knockdown in motoneurons in Drosophila, demonstrating neuromuscular junction (# of satellite boutons) and motility defects (climbing distance/velocity).

Overall this gene can be considered for inclusion with (probably) green rating in gene panels for ID, metabolic / mitochondrial disorders, cardiomyopathy, congenital microcephaly, corpus callosum anomalies, etc.
Sources: Literature
Bardet Biedl syndrome v0.78 IFT172 Zornitza Stark Marked gene: IFT172 as ready
Bardet Biedl syndrome v0.78 IFT172 Zornitza Stark Gene: ift172 has been classified as Green List (High Evidence).
Bardet Biedl syndrome v0.78 IFT172 Zornitza Stark Phenotypes for gene: IFT172 were changed from to Bardet-Biedl syndrome
Bardet Biedl syndrome v0.77 IFT172 Zornitza Stark Publications for gene: IFT172 were set to
Bardet Biedl syndrome v0.76 IFT172 Zornitza Stark Mode of inheritance for gene: IFT172 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Bardet Biedl syndrome v0.75 MKS1 Zornitza Stark Marked gene: MKS1 as ready
Bardet Biedl syndrome v0.75 MKS1 Zornitza Stark Gene: mks1 has been classified as Green List (High Evidence).
Bardet Biedl syndrome v0.75 MKS1 Zornitza Stark Phenotypes for gene: MKS1 were changed from to Bardet-Biedl syndrome 13, MIM# 615990
Bardet Biedl syndrome v0.74 MKS1 Zornitza Stark Publications for gene: MKS1 were set to
Bardet Biedl syndrome v0.73 MKS1 Zornitza Stark Mode of inheritance for gene: MKS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Bardet Biedl syndrome v0.72 MKS1 Zornitza Stark reviewed gene: MKS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 18327255, 24608809; Phenotypes: Bardet-Biedl syndrome 13, MIM# 615990; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Bardet Biedl syndrome v0.72 BBS9 Zornitza Stark Marked gene: BBS9 as ready
Bardet Biedl syndrome v0.72 BBS9 Zornitza Stark Gene: bbs9 has been classified as Green List (High Evidence).
Bardet Biedl syndrome v0.72 BBS9 Zornitza Stark Phenotypes for gene: BBS9 were changed from to Bardet-Biedl syndrome 9, MIM#615986
Bardet Biedl syndrome v0.71 BBS9 Zornitza Stark Publications for gene: BBS9 were set to
Bardet Biedl syndrome v0.70 BBS9 Zornitza Stark Mode of inheritance for gene: BBS9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Bardet Biedl syndrome v0.69 BBS9 Zornitza Stark reviewed gene: BBS9: Rating: GREEN; Mode of pathogenicity: None; Publications: 16380913, 22353939, 32686083, 32037757; Phenotypes: Bardet-Biedl syndrome 9, MIM#615986; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Bardet Biedl syndrome v0.69 BBS7 Zornitza Stark Marked gene: BBS7 as ready
Bardet Biedl syndrome v0.69 BBS7 Zornitza Stark Gene: bbs7 has been classified as Green List (High Evidence).
Bardet Biedl syndrome v0.69 BBS7 Zornitza Stark Phenotypes for gene: BBS7 were changed from to Bardet-Biedl syndrome 7, MIM# 615984
Bardet Biedl syndrome v0.68 BBS7 Zornitza Stark Publications for gene: BBS7 were set to
Bardet Biedl syndrome v0.67 BBS7 Zornitza Stark Mode of inheritance for gene: BBS7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Bardet Biedl syndrome v0.66 BBS7 Zornitza Stark reviewed gene: BBS7: Rating: GREEN; Mode of pathogenicity: None; Publications: 12567324, 21937992, 19797195; Phenotypes: Bardet-Biedl syndrome 7, MIM# 615984; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Syndromic Retinopathy v0.103 EXOSC2 Zornitza Stark Marked gene: EXOSC2 as ready
Syndromic Retinopathy v0.103 EXOSC2 Zornitza Stark Gene: exosc2 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.103 EXOSC2 Zornitza Stark Phenotypes for gene: EXOSC2 were changed from to Short stature, hearing loss, retinitis pigmentosa, and distinctive facies, MIM# 617763
Syndromic Retinopathy v0.102 EXOSC2 Zornitza Stark Publications for gene: EXOSC2 were set to
Syndromic Retinopathy v0.101 EXOSC2 Zornitza Stark Mode of inheritance for gene: EXOSC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4871 DHX38 Zornitza Stark Marked gene: DHX38 as ready
Mendeliome v0.4871 DHX38 Zornitza Stark Gene: dhx38 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4871 DHX38 Zornitza Stark Phenotypes for gene: DHX38 were changed from to Retinitis pigmentosa 84, MIM# 618220
Mendeliome v0.4870 DHX38 Zornitza Stark Publications for gene: DHX38 were set to
Mendeliome v0.4869 DHX38 Zornitza Stark Mode of inheritance for gene: DHX38 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4868 DHX38 Zornitza Stark Classified gene: DHX38 as Amber List (moderate evidence)
Mendeliome v0.4868 DHX38 Zornitza Stark Gene: dhx38 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4867 DHX38 Zornitza Stark reviewed gene: DHX38: Rating: AMBER; Mode of pathogenicity: None; Publications: 24737827, 30208423; Phenotypes: Retinitis pigmentosa 84, MIM# 618220; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinitis pigmentosa v0.69 DHX38 Zornitza Stark Marked gene: DHX38 as ready
Retinitis pigmentosa v0.69 DHX38 Zornitza Stark Gene: dhx38 has been classified as Amber List (Moderate Evidence).
Retinitis pigmentosa v0.69 DHX38 Zornitza Stark Phenotypes for gene: DHX38 were changed from Retinitis pigmentosa 84, 618220 to Retinitis pigmentosa 84, MIM#618220
Retinitis pigmentosa v0.68 DHX38 Zornitza Stark Publications for gene: DHX38 were set to
Retinitis pigmentosa v0.67 DHX38 Zornitza Stark Classified gene: DHX38 as Amber List (moderate evidence)
Retinitis pigmentosa v0.67 DHX38 Zornitza Stark Gene: dhx38 has been classified as Amber List (Moderate Evidence).
Retinitis pigmentosa v0.66 DHX38 Zornitza Stark reviewed gene: DHX38: Rating: AMBER; Mode of pathogenicity: None; Publications: 24737827, 30208423; Phenotypes: Retinitis pigmentosa 84, MIM# 618220; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Macular Dystrophy/Stargardt Disease v0.24 CTNNA1 Zornitza Stark edited their review of gene: CTNNA1: Changed rating: GREEN
Macular Dystrophy/Stargardt Disease v0.24 CTNNA1 Zornitza Stark reviewed gene: CTNNA1: Rating: ; Mode of pathogenicity: None; Publications: 26691986; Phenotypes: Macular dystrophy, butterfly-shaped pigmentary, 2, MIM# 608970; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4867 CCT2 Zornitza Stark Marked gene: CCT2 as ready
Mendeliome v0.4867 CCT2 Zornitza Stark Gene: cct2 has been classified as Red List (Low Evidence).
Mendeliome v0.4867 CCT2 Zornitza Stark gene: CCT2 was added
gene: CCT2 was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: CCT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCT2 were set to 27645772; 29450543
Phenotypes for gene: CCT2 were set to Leber's congenital amaurosis
Review for gene: CCT2 was set to RED
Added comment: Single family reported with compound het missense variants, functional data, including animal model.
Sources: NHS GMS
Retinitis pigmentosa v0.66 CCT2 Zornitza Stark Marked gene: CCT2 as ready
Retinitis pigmentosa v0.66 CCT2 Zornitza Stark Gene: cct2 has been classified as Red List (Low Evidence).
Retinitis pigmentosa v0.66 CCT2 Zornitza Stark gene: CCT2 was added
gene: CCT2 was added to Retinitis pigmentosa_Autosomal Recessive/X-linked. Sources: NHS GMS
Mode of inheritance for gene: CCT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCT2 were set to 27645772; 29450543
Phenotypes for gene: CCT2 were set to Leber's congenital amaurosis
Review for gene: CCT2 was set to RED
Added comment: Single family reported with compound het missense variants, functional data, including animal model.
Sources: NHS GMS
Mendeliome v0.4866 CA4 Zornitza Stark Marked gene: CA4 as ready
Mendeliome v0.4866 CA4 Zornitza Stark Gene: ca4 has been classified as Red List (Low Evidence).
Mendeliome v0.4866 CA4 Zornitza Stark Phenotypes for gene: CA4 were changed from to Retinitis pigmentosa 17, MIM# 600852
Mendeliome v0.4865 CA4 Zornitza Stark Publications for gene: CA4 were set to
Mendeliome v0.4864 CA4 Zornitza Stark Mode of inheritance for gene: CA4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4863 CA4 Zornitza Stark Classified gene: CA4 as Red List (low evidence)
Mendeliome v0.4863 CA4 Zornitza Stark Gene: ca4 has been classified as Red List (Low Evidence).
Mendeliome v0.4862 CA4 Zornitza Stark reviewed gene: CA4: Rating: RED; Mode of pathogenicity: None; Publications: 15563508, 15090652, 17652713, 16260723; Phenotypes: Retinitis pigmentosa 17, MIM# 600852; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Syndromic Retinopathy v0.100 AIRE Zornitza Stark Marked gene: AIRE as ready
Syndromic Retinopathy v0.100 AIRE Zornitza Stark Gene: aire has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.100 AIRE Zornitza Stark Classified gene: AIRE as Green List (high evidence)
Syndromic Retinopathy v0.100 AIRE Zornitza Stark Gene: aire has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.99 AIRE Zornitza Stark gene: AIRE was added
gene: AIRE was added to Syndromic Retinopathy. Sources: NHS GMS
Mode of inheritance for gene: AIRE was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: AIRE were set to 27606815
Phenotypes for gene: AIRE were set to Autoimmune polyendocrinopathy syndrome , type I, with or without reversible metaphyseal dysplasia, MIM# 240300
Review for gene: AIRE was set to GREEN
Added comment: Retinopathy is a feature: peripheral pigmentary changes are noted in all cases, ranging from isolated patchy atrophy of the retinal pigment epithelium to a retinitis pigmentosa-like fundus. Macular atrophy with vision loss is found in most. The severity of ophthalmic findings is uncorrelated to that of systemic manifestations. An autoimmune origin with specific autoantibodies directed against corneal and/or retinal autoantigens is the main mechanism believed to be responsible for the ocular manifestations of APS1.
Sources: NHS GMS
Syndromic Retinopathy v0.98 ABCC6 Zornitza Stark Marked gene: ABCC6 as ready
Syndromic Retinopathy v0.98 ABCC6 Zornitza Stark Gene: abcc6 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.98 ABCC6 Zornitza Stark Phenotypes for gene: ABCC6 were changed from to Pseudoxanthoma elasticum, MIM#264800
Syndromic Retinopathy v0.97 ABCC6 Zornitza Stark Mode of inheritance for gene: ABCC6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Syndromic Retinopathy v0.96 ABCC6 Zornitza Stark reviewed gene: ABCC6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pseudoxanthoma elasticum, MIM#264800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Bardet Biedl syndrome v0.66 BBS5 Zornitza Stark Marked gene: BBS5 as ready
Bardet Biedl syndrome v0.66 BBS5 Zornitza Stark Gene: bbs5 has been classified as Green List (High Evidence).
Bardet Biedl syndrome v0.66 BBS5 Zornitza Stark Phenotypes for gene: BBS5 were changed from to Bardet-Biedl syndrome 5, MIM#615983
Bardet Biedl syndrome v0.65 BBS5 Zornitza Stark Publications for gene: BBS5 were set to
Bardet Biedl syndrome v0.64 BBS5 Zornitza Stark Mode of inheritance for gene: BBS5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Bardet Biedl syndrome v0.63 BBS5 Zornitza Stark reviewed gene: BBS5: Rating: GREEN; Mode of pathogenicity: None; Publications: 19252258, 15137946, 10053027, 15637713; Phenotypes: Bardet-Biedl syndrome 5, MIM#615983; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Bardet Biedl syndrome v0.63 BBS4 Zornitza Stark Marked gene: BBS4 as ready
Bardet Biedl syndrome v0.63 BBS4 Zornitza Stark Gene: bbs4 has been classified as Green List (High Evidence).
Bardet Biedl syndrome v0.63 BBS4 Zornitza Stark Phenotypes for gene: BBS4 were changed from to Bardet-Biedl syndrome 4, MIM#615982
Bardet Biedl syndrome v0.62 BBS4 Zornitza Stark Publications for gene: BBS4 were set to
Bardet Biedl syndrome v0.61 BBS4 Zornitza Stark Mode of inheritance for gene: BBS4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Bardet Biedl syndrome v0.60 BBS4 Zornitza Stark reviewed gene: BBS4: Rating: GREEN; Mode of pathogenicity: None; Publications: 12016587, 11381270; Phenotypes: Bardet-Biedl syndrome 4, MIM#615982; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3062 VPS41 Zornitza Stark Marked gene: VPS41 as ready
Intellectual disability syndromic and non-syndromic v0.3062 VPS41 Zornitza Stark Gene: vps41 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.3062 VPS41 Zornitza Stark gene: VPS41 was added
gene: VPS41 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: VPS41 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS41 were set to 32808683
Phenotypes for gene: VPS41 were set to Dystonia; intellectual disability
Review for gene: VPS41 was set to RED
Added comment: Single individual reported with homozygous canonical splice site variant resulting in exon 7 skipping, and global developmental delay and generalized dystonia. He attained a few words and voluntary limb movements but never sat unsupported. He had pale optic discs and an axonal neuropathy. From 6 years of age, his condition began to deteriorate, with reduced motor abilities and alertness. An MRI of the brain showed atrophy of the superior cerebellar vermis and slimming of the posterior limb of the corpus callosum. VPS41 is component of the HOPS complex and other genes in the complex have been implicated in movement disorders.
Sources: Literature
Mendeliome v0.4862 VPS41 Zornitza Stark Marked gene: VPS41 as ready
Mendeliome v0.4862 VPS41 Zornitza Stark Gene: vps41 has been classified as Red List (Low Evidence).
Mendeliome v0.4862 VPS41 Zornitza Stark gene: VPS41 was added
gene: VPS41 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: VPS41 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS41 were set to 32808683
Phenotypes for gene: VPS41 were set to Dystonia; intellectual disability
Review for gene: VPS41 was set to RED
Added comment: Single individual reported with homozygous canonical splice site variant resulting in exon 7 skipping, and global developmental delay and generalized dystonia. He attained a few words and voluntary limb movements but never sat unsupported. He had pale optic discs and an axonal neuropathy. From 6 years of age, his condition began to deteriorate, with reduced motor abilities and alertness. An MRI of the brain showed atrophy of the superior cerebellar vermis and slimming of the posterior limb of the corpus callosum. VPS41 is component of the HOPS complex and other genes in the complex have been implicated in movement disorders.
Sources: Literature
Dystonia and Chorea v0.149 VPS41 Zornitza Stark Marked gene: VPS41 as ready
Dystonia and Chorea v0.149 VPS41 Zornitza Stark Gene: vps41 has been classified as Red List (Low Evidence).
Dystonia and Chorea v0.149 VPS41 Zornitza Stark gene: VPS41 was added
gene: VPS41 was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: VPS41 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS41 were set to 32808683
Phenotypes for gene: VPS41 were set to Dystonia; intellectual disability
Review for gene: VPS41 was set to RED
Added comment: Single individual reported with homozygous canonical splice site variant resulting in exon 7 skipping, and global developmental delay and generalized dystonia. He attained a few words and voluntary limb movements but never sat unsupported. He had pale optic discs and an axonal neuropathy. From 6 years of age, his condition began to deteriorate, with reduced motor abilities and alertness. An MRI of the brain showed atrophy of the superior cerebellar vermis and slimming of the posterior limb of the corpus callosum. VPS41 is component of the HOPS complex and other genes in the complex have been implicated in movement disorders.
Sources: Literature
Mendeliome v0.4861 VPS16 Zornitza Stark edited their review of gene: VPS16: Changed rating: GREEN
Mendeliome v0.4861 VPS16 Zornitza Stark Marked gene: VPS16 as ready
Mendeliome v0.4861 VPS16 Zornitza Stark Gene: vps16 has been classified as Green List (High Evidence).
Mendeliome v0.4861 VPS16 Zornitza Stark Classified gene: VPS16 as Green List (high evidence)
Mendeliome v0.4861 VPS16 Zornitza Stark Gene: vps16 has been classified as Green List (High Evidence).
Mendeliome v0.4860 VPS16 Zornitza Stark gene: VPS16 was added
gene: VPS16 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: VPS16 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VPS16 were set to 32808683
Phenotypes for gene: VPS16 were set to Dystonia
Added comment: 18 individuals reported with high-impact variants in VPS16 and a progressive early onset dystonia (median age 12 years, range 3–50 years), with prominent oromandibular, bulbar, cervical, and upper limb involvement. Progressive generalization ensued, although most remained ambulant, and only a minority (16%) lost the ability to walk in adulthood. Additional clinical features of mild to moderate intellectual disability and neuropsychiatric symptoms were present in approximately one‐third. In 4 individuals, magnetic resonance imaging (MRI) showed bilateral and symmetrical hypointensity of the globi pallidi and sometimes also the midbrain and dentate nuclei, suggestive of iron deposition. Mild generalized cerebral atrophy was also apparent in 4 individuals.
Sources: Literature
Dystonia and Chorea v0.148 VPS16 Zornitza Stark Marked gene: VPS16 as ready
Dystonia and Chorea v0.148 VPS16 Zornitza Stark Gene: vps16 has been classified as Green List (High Evidence).
Dystonia and Chorea v0.148 VPS16 Zornitza Stark Classified gene: VPS16 as Green List (high evidence)
Dystonia and Chorea v0.148 VPS16 Zornitza Stark Gene: vps16 has been classified as Green List (High Evidence).
Dystonia and Chorea v0.147 VPS16 Zornitza Stark gene: VPS16 was added
gene: VPS16 was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: VPS16 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VPS16 were set to 32808683
Phenotypes for gene: VPS16 were set to Dystonia
Review for gene: VPS16 was set to GREEN
Added comment: 18 individuals reported with high-impact variants in VPS16 and a progressive early onset dystonia (median age 12 years, range 3–50 years), with prominent oromandibular, bulbar, cervical, and upper limb involvement. Progressive generalization ensued, although most remained ambulant, and only a minority (16%) lost the ability to walk in adulthood.

Additional clinical features of mild to moderate intellectual disability and neuropsychiatric symptoms were present in approximately one‐third. In 4 individuals, magnetic resonance imaging (MRI) showed bilateral and symmetrical hypointensity of the globi pallidi and sometimes also the midbrain and dentate nuclei, suggestive of iron deposition. Mild generalized cerebral atrophy was also apparent in 4 individuals.
Sources: Literature
Bardet Biedl syndrome v0.60 BBS2 Zornitza Stark Marked gene: BBS2 as ready
Bardet Biedl syndrome v0.60 BBS2 Zornitza Stark Gene: bbs2 has been classified as Green List (High Evidence).
Bardet Biedl syndrome v0.60 BBS2 Zornitza Stark Phenotypes for gene: BBS2 were changed from to Bardet-Biedl syndrome 2, MIM# 615981
Bardet Biedl syndrome v0.59 BBS2 Zornitza Stark Publications for gene: BBS2 were set to
Bardet Biedl syndrome v0.58 BBS2 Zornitza Stark Mode of inheritance for gene: BBS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Bardet Biedl syndrome v0.57 BBS2 Zornitza Stark reviewed gene: BBS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 11567139, 16823392, 28143435; Phenotypes: Bardet-Biedl syndrome 2, MIM# 615981; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Macular Dystrophy/Stargardt Disease v0.24 CFH Zornitza Stark Marked gene: CFH as ready
Macular Dystrophy/Stargardt Disease v0.24 CFH Zornitza Stark Gene: cfh has been classified as Green List (High Evidence).
Macular Dystrophy/Stargardt Disease v0.24 CFH Zornitza Stark Phenotypes for gene: CFH were changed from {Macular degeneration, age-related, 4} 610698; Basal laminar drusen, 126700 to Basal laminar drusen, 126700
Macular Dystrophy/Stargardt Disease v0.23 CFH Zornitza Stark Publications for gene: CFH were set to
Macular Dystrophy/Stargardt Disease v0.22 PRDM13 Zornitza Stark Mode of pathogenicity for gene: PRDM13 was changed from to Other
Macular Dystrophy/Stargardt Disease v0.21 PRDM13 Zornitza Stark Mode of inheritance for gene: PRDM13 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Macular Dystrophy/Stargardt Disease v0.20 RBP3 Zornitza Stark Marked gene: RBP3 as ready
Macular Dystrophy/Stargardt Disease v0.20 RBP3 Zornitza Stark Gene: rbp3 has been classified as Amber List (Moderate Evidence).
Macular Dystrophy/Stargardt Disease v0.20 RBP3 Zornitza Stark Phenotypes for gene: RBP3 were changed from ?Retinitis pigmentosa 66, 615233 to Retinitis pigmentosa 66, 615233
Macular Dystrophy/Stargardt Disease v0.19 RBP3 Zornitza Stark Publications for gene: RBP3 were set to
Macular Dystrophy/Stargardt Disease v0.18 FSCN2 Zornitza Stark Marked gene: FSCN2 as ready
Macular Dystrophy/Stargardt Disease v0.18 FSCN2 Zornitza Stark Gene: fscn2 has been classified as Red List (Low Evidence).
Macular Dystrophy/Stargardt Disease v0.18 FSCN2 Zornitza Stark Publications for gene: FSCN2 were set to
Macular Dystrophy/Stargardt Disease v0.17 PITPNM3 Zornitza Stark Marked gene: PITPNM3 as ready
Macular Dystrophy/Stargardt Disease v0.17 PITPNM3 Zornitza Stark Gene: pitpnm3 has been classified as Red List (Low Evidence).
Macular Dystrophy/Stargardt Disease v0.17 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Macular Dystrophy/Stargardt Disease v0.16 RS1 Zornitza Stark Marked gene: RS1 as ready
Macular Dystrophy/Stargardt Disease v0.16 RS1 Zornitza Stark Gene: rs1 has been classified as Green List (High Evidence).
Macular Dystrophy/Stargardt Disease v0.16 RS1 Zornitza Stark Phenotypes for gene: RS1 were changed from Developmental macular and foveal dystrophy (males with foveal schisis) to Retinoschisis, MIM#312700; Developmental macular and foveal dystrophy (males with foveal schisis)
Macular Dystrophy/Stargardt Disease v0.15 RS1 Zornitza Stark Publications for gene: RS1 were set to
Macular Dystrophy/Stargardt Disease v0.14 RS1 Zornitza Stark Mode of inheritance for gene: RS1 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Macular Dystrophy/Stargardt Disease v0.13 RS1 Zornitza Stark reviewed gene: RS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15932525, 23453514, 23847049; Phenotypes: Retinoschisis, MIM#312700; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Syndromic Retinopathy v0.96 MFSD8 Zornitza Stark Marked gene: MFSD8 as ready
Syndromic Retinopathy v0.96 MFSD8 Zornitza Stark Gene: mfsd8 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.96 MFSD8 Zornitza Stark Classified gene: MFSD8 as Green List (high evidence)
Syndromic Retinopathy v0.96 MFSD8 Zornitza Stark Gene: mfsd8 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.95 MFSD8 Zornitza Stark gene: MFSD8 was added
gene: MFSD8 was added to Syndromic Retinopathy. Sources: Expert Review
Mode of inheritance for gene: MFSD8 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MFSD8 were set to Ceroid lipofuscinosis, neuronal, 7 OMIM #610951
Review for gene: MFSD8 was set to GREEN
Added comment: Retinal degeneration is part of the phenotype.
Sources: Expert Review
Syndromic Retinopathy v0.94 ACBD5 Zornitza Stark Marked gene: ACBD5 as ready
Syndromic Retinopathy v0.94 ACBD5 Zornitza Stark Gene: acbd5 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.94 ACBD5 Zornitza Stark Phenotypes for gene: ACBD5 were changed from to Retinal dystrophy with leukodystrophy (MIM#618863)
Syndromic Retinopathy v0.93 ACBD5 Zornitza Stark Mode of inheritance for gene: ACBD5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Syndromic Retinopathy v0.92 ACBD5 Zornitza Stark 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
Syndromic Retinopathy v0.92 TPP1 Zornitza Stark Marked gene: TPP1 as ready
Syndromic Retinopathy v0.92 TPP1 Zornitza Stark Gene: tpp1 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.92 TPP1 Zornitza Stark Classified gene: TPP1 as Green List (high evidence)
Syndromic Retinopathy v0.92 TPP1 Zornitza Stark Gene: tpp1 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.91 TPP1 Zornitza Stark gene: TPP1 was added
gene: TPP1 was added to Syndromic Retinopathy. Sources: Expert Review
Mode of inheritance for gene: TPP1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TPP1 were set to Ceroid lipofuscinosis, neuronal, 2, OMIM #204500
Review for gene: TPP1 was set to GREEN
Added comment: Retinal degeneration is part of the phenotype.
Sources: Expert Review
Syndromic Retinopathy v0.90 PPT1 Zornitza Stark Marked gene: PPT1 as ready
Syndromic Retinopathy v0.90 PPT1 Zornitza Stark Gene: ppt1 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.90 PPT1 Zornitza Stark Classified gene: PPT1 as Green List (high evidence)
Syndromic Retinopathy v0.90 PPT1 Zornitza Stark Gene: ppt1 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.89 PPT1 Zornitza Stark gene: PPT1 was added
gene: PPT1 was added to Syndromic Retinopathy. Sources: Expert Review
Mode of inheritance for gene: PPT1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PPT1 were set to Ceroid lipofuscinosis, neuronal, 1, MIM#256730
Review for gene: PPT1 was set to GREEN
Added comment: Retinal degeneration is part of the phenotype.
Sources: Expert Review
Syndromic Retinopathy v0.88 GRN Zornitza Stark Marked gene: GRN as ready
Syndromic Retinopathy v0.88 GRN Zornitza Stark Gene: grn has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.88 GRN Zornitza Stark Classified gene: GRN as Green List (high evidence)
Syndromic Retinopathy v0.88 GRN Zornitza Stark Gene: grn has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.87 GRN Zornitza Stark gene: GRN was added
gene: GRN was added to Syndromic Retinopathy. Sources: Expert Review
Mode of inheritance for gene: GRN was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GRN were set to Ceroid lipofuscinosis, neuronal, 11, OMIM #614706
Review for gene: GRN was set to GREEN
Added comment: Retinal degeneration is part of the phenotype.
Sources: Expert Review
Syndromic Retinopathy v0.86 CTSF Zornitza Stark Marked gene: CTSF as ready
Syndromic Retinopathy v0.86 CTSF Zornitza Stark Gene: ctsf has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.86 CTSF Zornitza Stark Classified gene: CTSF as Green List (high evidence)
Syndromic Retinopathy v0.86 CTSF Zornitza Stark Gene: ctsf has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.85 CTSF Zornitza Stark gene: CTSF was added
gene: CTSF was added to Syndromic Retinopathy. Sources: Expert Review
Mode of inheritance for gene: CTSF was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CTSF were set to Ceroid lipofuscinosis, neuronal, 13, Kufs type OMIM #615362
Review for gene: CTSF was set to GREEN
Added comment: Retinal degeneration is a feature.
Sources: Expert Review
Syndromic Retinopathy v0.84 CTSD Zornitza Stark Marked gene: CTSD as ready
Syndromic Retinopathy v0.84 CTSD Zornitza Stark Gene: ctsd has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.84 CTSD Zornitza Stark Classified gene: CTSD as Green List (high evidence)
Syndromic Retinopathy v0.84 CTSD Zornitza Stark Gene: ctsd has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.83 CTSD Zornitza Stark gene: CTSD was added
gene: CTSD was added to Syndromic Retinopathy. Sources: Expert Review
Mode of inheritance for gene: CTSD was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CTSD were set to Ceroid lipofuscinosis, neuronal, 10, OMIM #610127
Review for gene: CTSD was set to GREEN
Added comment: Retinal degeneration is part of the phenotype.
Sources: Expert Review
Syndromic Retinopathy v0.82 CLN8 Zornitza Stark Marked gene: CLN8 as ready
Syndromic Retinopathy v0.82 CLN8 Zornitza Stark Gene: cln8 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.82 CLN8 Zornitza Stark Classified gene: CLN8 as Green List (high evidence)
Syndromic Retinopathy v0.82 CLN8 Zornitza Stark Gene: cln8 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.81 CLN8 Zornitza Stark gene: CLN8 was added
gene: CLN8 was added to Syndromic Retinopathy. Sources: Expert Review
Mode of inheritance for gene: CLN8 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CLN8 were set to Ceroid lipofuscinosis, neuronal, 8 OMIM #600143
Review for gene: CLN8 was set to GREEN
Added comment: Retinal degeneration is part of the phenotype.
Sources: Expert Review
Syndromic Retinopathy v0.80 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Syndromic Retinopathy v0.79 CLN6 Zornitza Stark Marked gene: CLN6 as ready
Syndromic Retinopathy v0.79 CLN6 Zornitza Stark Gene: cln6 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.79 CLN6 Zornitza Stark Classified gene: CLN6 as Green List (high evidence)
Syndromic Retinopathy v0.79 CLN6 Zornitza Stark Gene: cln6 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.78 CLN6 Zornitza Stark gene: CLN6 was added
gene: CLN6 was added to Syndromic Retinopathy. Sources: Expert Review
Mode of inheritance for gene: CLN6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CLN6 were set to Ceroid lipofuscinosis, neuronal, 6 OMIM #601780
Review for gene: CLN6 was set to GREEN
Added comment: Retinal degeneration is a feature.
Sources: Expert Review
Syndromic Retinopathy v0.77 CLN5 Zornitza Stark Marked gene: CLN5 as ready
Syndromic Retinopathy v0.77 CLN5 Zornitza Stark Gene: cln5 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.77 CLN5 Zornitza Stark Classified gene: CLN5 as Green List (high evidence)
Syndromic Retinopathy v0.77 CLN5 Zornitza Stark Gene: cln5 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.76 CLN5 Zornitza Stark gene: CLN5 was added
gene: CLN5 was added to Syndromic Retinopathy. Sources: Expert Review
Mode of inheritance for gene: CLN5 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CLN5 were set to Ceroid lipofuscinosis, neuronal, 5 OMIM #256731
Review for gene: CLN5 was set to GREEN
Added comment: Retinal degeneration is a feature.
Sources: Expert Review
Cerebral vascular malformations v0.6 KRIT1 Zornitza Stark Marked gene: KRIT1 as ready
Cerebral vascular malformations v0.6 KRIT1 Zornitza Stark Gene: krit1 has been classified as Green List (High Evidence).
Cerebral vascular malformations v0.6 KRIT1 Zornitza Stark Phenotypes for gene: KRIT1 were changed from Cerebral cavernous malformations 1; Cerebral cavernous malformations-1, 116860; Cerebral Cavernous Malformations; Cerebral Cavernous Malformation; Angiokeratoma Corporis Diffusum with Arteriovenous Fistulas; Familial Cerebral Cavernous Malformation; Hyperkeratotic cutaneous capillary-venous malformations associated with cerebral capillary malformations, 116860 to Cavernous malformations of CNS and retina, 116860; Cerebral cavernous malformations-1, 116860; Hyperkeratotic cutaneous capillary-venous malformations associated with cerebral capillary malformations, 116860
Cerebral vascular malformations v0.5 KRIT1 Zornitza Stark Tag founder tag was added to gene: KRIT1.
Cerebral vascular malformations v0.5 KRIT1 Zornitza Stark Mode of inheritance for gene: KRIT1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4859 KRIT1 Zornitza Stark Tag founder tag was added to gene: KRIT1.
Vascular Malformations_Germline v0.113 KRIT1 Zornitza Stark Tag founder tag was added to gene: KRIT1.
Vascular Malformations_Germline v0.113 KRIT1 Zornitza Stark changed review comment from: Mutations in KRIT1 are predominantly nonsense or frameshift mutations resulting in premature stop codons (PMID: 29593473). Incomplete penetrance observed in inherited CCM (PMID: 16571644; OMIM)

American-Hispanic founder mutation: c.1363C>T, p.Gln455*/Q248* (OMIM). Sardinian founder mutation: C329X (OMIM); to: American-Hispanic founder mutation: c.1363C>T, p.Gln455*/Q248* (OMIM). Sardinian founder mutation: C329X (OMIM)
Vascular Malformations_Germline v0.113 KRIT1 Zornitza Stark changed review comment from: Mutations in KRIT1 are predominantly nonsense or frameshift mutations resulting in premature stop codons (PMID: 29593473). Incomplete penetrance observed in inherited CCM (PMID: 16571644; OMIM); to: Mutations in KRIT1 are predominantly nonsense or frameshift mutations resulting in premature stop codons (PMID: 29593473). Incomplete penetrance observed in inherited CCM (PMID: 16571644; OMIM)

American-Hispanic founder mutation: c.1363C>T, p.Gln455*/Q248* (OMIM). Sardinian founder mutation: C329X (OMIM)
Cerebral vascular malformations v0.4 KRIT1 Zornitza Stark reviewed gene: KRIT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 16571644, 29593473; Phenotypes: Cavernous malformations of CNS and retina, 116860, Cerebral cavernous malformations-1, 116860, Hyperkeratotic cutaneous capillary-venous malformations associated with cerebral capillary malformations, 116860; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4859 KRIT1 Zornitza Stark Marked gene: KRIT1 as ready
Mendeliome v0.4859 KRIT1 Zornitza Stark Gene: krit1 has been classified as Green List (High Evidence).
Mendeliome v0.4859 KRIT1 Zornitza Stark Phenotypes for gene: KRIT1 were changed from to Cavernous malformations of CNS and retina, 116860; Cerebral cavernous malformations-1, 116860; Hyperkeratotic cutaneous capillary-venous malformations associated with cerebral capillary malformations, 116860
Mendeliome v0.4858 KRIT1 Zornitza Stark Publications for gene: KRIT1 were set to
Mendeliome v0.4857 KRIT1 Zornitza Stark Mode of inheritance for gene: KRIT1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4856 SH3TC2 Zornitza Stark Marked gene: SH3TC2 as ready
Mendeliome v0.4856 SH3TC2 Zornitza Stark Gene: sh3tc2 has been classified as Green List (High Evidence).
Mendeliome v0.4856 SH3TC2 Zornitza Stark Phenotypes for gene: SH3TC2 were changed from to Charcot-Marie-Tooth disease, type 4C MIM#601596, Mononeuropathy of the median nerve, mild MIM#613353
Mendeliome v0.4855 SH3TC2 Zornitza Stark Publications for gene: SH3TC2 were set to
Mendeliome v0.4854 SH3TC2 Zornitza Stark Mode of inheritance for gene: SH3TC2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4853 SH3TC2 Zornitza Stark reviewed gene: SH3TC2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Vascular Malformations_Germline v0.113 EPHB4 Zornitza Stark Marked gene: EPHB4 as ready
Vascular Malformations_Germline v0.113 EPHB4 Zornitza Stark Gene: ephb4 has been classified as Green List (High Evidence).
Vascular Malformations_Germline v0.113 EPHB4 Zornitza Stark Publications for gene: EPHB4 were set to
Vascular Malformations_Germline v0.112 EPHB4 Zornitza Stark Mode of inheritance for gene: EPHB4 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4853 ABCC6 Zornitza Stark Marked gene: ABCC6 as ready
Mendeliome v0.4853 ABCC6 Zornitza Stark Added comment: Comment when marking as ready: Evidence for mono-allelic variants causing disease is limited.
Mendeliome v0.4853 ABCC6 Zornitza Stark Gene: abcc6 has been classified as Green List (High Evidence).
Mendeliome v0.4853 ABCC6 Zornitza Stark Tag SV/CNV tag was added to gene: ABCC6.
Mendeliome v0.4853 CAPN3 Zornitza Stark Marked gene: CAPN3 as ready
Mendeliome v0.4853 CAPN3 Zornitza Stark Gene: capn3 has been classified as Green List (High Evidence).
Mendeliome v0.4853 CAPN3 Zornitza Stark Phenotypes for gene: CAPN3 were changed from to Muscular dystrophy, limb-girdle, autosomal dominant 4, MIM# 618129; Muscular dystrophy, limb-girdle, autosomal recessive 1, MIM# 253600
Mendeliome v0.4852 CAPN3 Zornitza Stark Publications for gene: CAPN3 were set to
Mendeliome v0.4851 CAPN3 Zornitza Stark Mode of inheritance for gene: CAPN3 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.4850 CAPN3 Zornitza Stark reviewed gene: CAPN3: Rating: GREEN; Mode of pathogenicity: None; Publications: 31937337, 28881388, 32342993, 32557990; Phenotypes: Muscular dystrophy, limb-girdle, autosomal dominant 4, MIM# 618129, Muscular dystrophy, limb-girdle, autosomal recessive 1, MIM# 253600; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.56 CAPN3 Zornitza Stark Publications for gene: CAPN3 were set to 31937337; 28881388; 32342993
Paroxysmal Dyskinesia v0.85 SLC6A5 Zornitza Stark Marked gene: SLC6A5 as ready
Paroxysmal Dyskinesia v0.85 SLC6A5 Zornitza Stark Gene: slc6a5 has been classified as Green List (High Evidence).
Paroxysmal Dyskinesia v0.85 SLC6A5 Zornitza Stark Phenotypes for gene: SLC6A5 were changed from to Hyperekplexia 3, MIM# 614618
Paroxysmal Dyskinesia v0.84 SLC6A5 Zornitza Stark Publications for gene: SLC6A5 were set to
Paroxysmal Dyskinesia v0.83 SLC6A5 Zornitza Stark Mode of inheritance for gene: SLC6A5 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Paroxysmal Dyskinesia v0.82 SLC6A5 Zornitza Stark reviewed gene: SLC6A5: Rating: GREEN; Mode of pathogenicity: None; Publications: 31604777, 30847549, 29859229, 16751771; Phenotypes: Hyperekplexia 3, MIM# 614618; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4850 SLC6A5 Zornitza Stark Marked gene: SLC6A5 as ready
Mendeliome v0.4850 SLC6A5 Zornitza Stark Gene: slc6a5 has been classified as Green List (High Evidence).
Mendeliome v0.4850 SLC6A5 Zornitza Stark Phenotypes for gene: SLC6A5 were changed from to Hyperekplexia 3, MIM# 614618
Mendeliome v0.4849 KRIT1 Elena Savva reviewed gene: KRIT1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 16571644, 29593473; Phenotypes: Cavernous malformations of CNS and retina, 116860, Cerebral cavernous malformations-1, 116860, Hyperkeratotic cutaneous capillary-venous malformations associated with cerebral capillary malformations, 116860; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.4849 SLC6A5 Zornitza Stark Publications for gene: SLC6A5 were set to
Mendeliome v0.4848 SLC6A5 Zornitza Stark Mode of pathogenicity for gene: SLC6A5 was changed from to Other
Mendeliome v0.4847 SLC6A5 Zornitza Stark Mode of inheritance for gene: SLC6A5 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4846 SLC6A5 Zornitza Stark reviewed gene: SLC6A5: Rating: GREEN; Mode of pathogenicity: None; Publications: 31604777, 30847549, 29859229, 16751771; Phenotypes: Hyperekplexia 3, MIM# 614618; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4846 ARX Zornitza Stark Marked gene: ARX as ready
Mendeliome v0.4846 ARX Zornitza Stark Gene: arx has been classified as Green List (High Evidence).
Mendeliome v0.4846 ARX Zornitza Stark Phenotypes for gene: ARX were changed from to Epileptic encephalopathy, early infantile, 1 MIM#308350; Hydranencephaly with abnormal genitalia MIM#300215; Lissencephaly, X-linked 2 MIM#300215; Mental retardation, X-linked 29 and others MIM#300419; Partington syndrome MIM#309510; Proud syndrome MIM#300004
Mendeliome v0.4845 ARX Zornitza Stark Publications for gene: ARX were set to
Mendeliome v0.4844 ARX Zornitza Stark Mode of inheritance for gene: ARX 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)
Mendeliome v0.4843 SH3TC2 Elena Savva reviewed gene: SH3TC2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 19744956, 20220177, 19744956, 20028792; Phenotypes: Charcot-Marie-Tooth disease, type 4C MIM#601596, Mononeuropathy of the median nerve, mild MIM#613353; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Vascular Malformations_Germline v0.111 EPHB4 Kristin Rigbye reviewed gene: EPHB4: Rating: GREEN; Mode of pathogenicity: None; Publications: 27400125, 28687708, 29444212, 29905864, 30578106, 30819650; Phenotypes: Capillary malformation-arteriovenous malformation 2 (MIM#618196), AD, Lymphatic malformation 7 (MIM#617300), AD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4843 ABCC6 Kristin Rigbye changed review comment from: All conditions are regarded as a single disorder at variable ends of the phenotypic spectrum. The same variants have been reported in all three conditions, however reports for AD PE are consistently from older papers (pre-2005) and may have missed a 2nd hit (OMIM). More recent papers consistently report this condition as autosomal recessive (PMID: 28102862).; to: All conditions are regarded as a single disorder at variable ends of the phenotypic spectrum. The same variants have been reported in all three conditions, however reports for AD PXE are consistently from older papers (pre-2005) and may have missed a 2nd hit (OMIM). More recent papers consistently report this condition as autosomal recessive (PMID: 28102862).

In addition to missense, PTCs and splice variants, deletions and duplications in this gene comprise a significant proportion of variants and are a recognised mechanism / cause of PXE.
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.55 CAPN3 Kristin Rigbye edited their review of gene: CAPN3: Changed publications: 32557990, 32342993
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.55 CAPN3 Kristin Rigbye reviewed gene: CAPN3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32557990, 32342993; Phenotypes: CAPN3-related muscular dystrophy, AD, AR; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.55 CAPN3 Kristin Rigbye Deleted their review
Mendeliome v0.4843 SLC6A5 Elena Savva reviewed gene: SLC6A5: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 16751771; Phenotypes: Hyperekplexia 3 MIM#614618; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4843 ARX Elena Savva reviewed gene: ARX: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 14722918, 19738637, 32519823, 28150386, 21496008; Phenotypes: Epileptic encephalopathy, early infantile, 1 MIM#308350, Hydranencephaly with abnormal genitalia MIM#300215, Lissencephaly, X-linked 2 MIM#300215, Mental retardation, X-linked 29 and others MIM#300419, Partington syndrome MIM#309510, Proud syndrome MIM#300004; 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
Mendeliome v0.4843 TBL1Y Zornitza Stark Phenotypes for gene: TBL1Y were changed from Hearing loss to Deafness, Y-linked 2, MIM# 400047
Mendeliome v0.4842 TBL1Y Zornitza Stark edited their review of gene: TBL1Y: Changed rating: RED; Changed phenotypes: Deafness, Y-linked 2, MIM# 400047
Deafness_IsolatedAndComplex v1.10 TBL1Y Zornitza Stark Phenotypes for gene: TBL1Y were changed from Hearing loss to Deafness, Y-linked 2, MIM# 400047
Deafness_IsolatedAndComplex v1.9 TBL1Y Zornitza Stark edited their review of gene: TBL1Y: Changed phenotypes: Deafness, Y-linked 2, MIM# 400047
Mendeliome v0.4842 MCM2 Zornitza Stark Marked gene: MCM2 as ready
Mendeliome v0.4842 MCM2 Zornitza Stark Gene: mcm2 has been classified as Red List (Low Evidence).
Mendeliome v0.4842 MCM2 Zornitza Stark gene: MCM2 was added
gene: MCM2 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: MCM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MCM2 were set to 26196677
Phenotypes for gene: MCM2 were set to Deafness, autosomal dominant 70, MIM# 616968
Review for gene: MCM2 was set to RED
Added comment: One family, expression studies.
Sources: Expert Review
Deafness_IsolatedAndComplex v1.9 MCM2 Zornitza Stark Phenotypes for gene: MCM2 were changed from Autosomal dominant hearing loss to Deafness, autosomal dominant 70, MIM# 616968
Deafness_IsolatedAndComplex v1.8 MCM2 Zornitza Stark reviewed gene: MCM2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal dominant 70, MIM# 616968; Mode of inheritance: None
Deafness_IsolatedAndComplex v1.8 GJB4 Zornitza Stark Phenotypes for gene: GJB4 were changed from to Deafness
Deafness_IsolatedAndComplex v1.7 GJB4 Zornitza Stark edited their review of gene: GJB4: Changed phenotypes: Deafness
Deafness_IsolatedAndComplex v1.7 TMTC2 Zornitza Stark Phenotypes for gene: TMTC2 were changed from to Deafness, autosomal dominant
Deafness_IsolatedAndComplex v1.6 TUBB4B Zornitza Stark Phenotypes for gene: TUBB4B were changed from Leber congenital amaurosis with early-onset deafness to Leber congenital amaurosis with early-onset deafness, MIM# 617879
Deafness_IsolatedAndComplex v1.5 TUBB4B Zornitza Stark reviewed gene: TUBB4B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Leber congenital amaurosis with early-onset deafness, MIM# 617879; Mode of inheritance: None
Deafness_IsolatedAndComplex v1.5 SLC12A2 Zornitza Stark edited their review of gene: SLC12A2: Added comment: Second family with bi-allelic variants reported, encephalopathy and deafness.; Changed publications: 30740830, 32754646
Deafness_IsolatedAndComplex v1.5 PLOD3 Zornitza Stark Phenotypes for gene: PLOD3 were changed from Sensorineural deafness to Lysyl hydroxylase 3 deficiency, MIM# 612394; Sensorineural deafness
Deafness_IsolatedAndComplex v1.4 PLOD3 Zornitza Stark reviewed gene: PLOD3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Lysyl hydroxylase 3 deficiency, MIM# 612394; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v1.4 LMX1A Zornitza Stark Phenotypes for gene: LMX1A were changed from Deafness, autosomal recessive and autosomal dominant to Deafness, autosomal dominant 7 MIM#601412; Deafness, autosomal recessive
Deafness_IsolatedAndComplex v1.3 DMXL2 Zornitza Stark Phenotypes for gene: DMXL2 were changed from Autosomal dominant hearing loss; Epileptic encephalopathy, early infantile, 81, MIM#618663, includes deafness to Deafness, autosomal dominant 71, MIM#617605; Epileptic encephalopathy, early infantile, 81, MIM#618663, includes deafness
Deafness_IsolatedAndComplex v1.2 DMXL2 Zornitza Stark reviewed gene: DMXL2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal dominant 71, MIM#617605, Epileptic encephalopathy, early infantile, 81, MIM# 618663; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v1.2 AP1B1 Zornitza Stark Phenotypes for gene: AP1B1 were changed from Intellectual disability; enteropathy; deafness; ichthyosis; keratoderma to Keratitis-ichthyosis-deafness syndrome, autosomal recessive, MIM# 242150; Intellectual disability; enteropathy; deafness; ichthyosis; keratoderma
Deafness_IsolatedAndComplex v1.1 AP1B1 Zornitza Stark edited their review of gene: AP1B1: Changed phenotypes: Keratitis-ichthyosis-deafness syndrome, autosomal recessive, MIM# 242150, Intellectual disability, enteropathy, deafness, peripheral neuropathy, ichthyosis, keratoderma
Deafness_IsolatedAndComplex v1.1 ACTB Zornitza Stark Phenotypes for gene: ACTB were changed from Baraitser-Winter syndrome; Deafness-dystonia syndrome to Baraitser-Winter syndrome 1, MIM# 243310; Dystonia, juvenile-onset, MIM# 607371
Deafness_IsolatedAndComplex v1.0 ACTB Zornitza Stark reviewed gene: ACTB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Baraitser-Winter syndrome 1, MIM# 243310, Dystonia, juvenile-onset, MIM# 607371; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.876 SATB2 Zornitza Stark Marked gene: SATB2 as ready
Genetic Epilepsy v0.876 SATB2 Zornitza Stark Gene: satb2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.876 SATB2 Zornitza Stark Classified gene: SATB2 as Green List (high evidence)
Genetic Epilepsy v0.876 SATB2 Zornitza Stark Gene: satb2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.875 SATB2 Zornitza Stark gene: SATB2 was added
gene: SATB2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SATB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SATB2 were set to 32446642
Phenotypes for gene: SATB2 were set to Glass syndrome, MIM# 612313
Review for gene: SATB2 was set to GREEN
Added comment: In a cohort of 101 individuals with SATB2-associated syndrome, 41 had at least one prior abnormal EEG. Thirty-eight individuals (93%) had epileptiform discharges, 28 (74%) with central localization. Sleep stages were included as part of the electroencephalographies performed in 31 individuals (76%), and epileptiform activity was recorded during sleep in all instances (100%). Definite clinical seizures were diagnosed in 17 individuals (42%) with a mean age of onset of 3.2 years (four months to six years), and focal seizures were the most common type of seizure observed (42%). Six individuals with definite clinical seizures needed polytherapy (35%).
Sources: Literature
Alternating Hemiplegia and Hemiplegic Migraine v0.45 SLC2A1 Zornitza Stark Marked gene: SLC2A1 as ready
Alternating Hemiplegia and Hemiplegic Migraine v0.45 SLC2A1 Zornitza Stark Gene: slc2a1 has been classified as Green List (High Evidence).
Alternating Hemiplegia and Hemiplegic Migraine v0.45 SLC2A1 Zornitza Stark Phenotypes for gene: SLC2A1 were changed from to Hemiplegic migraine
Alternating Hemiplegia and Hemiplegic Migraine v0.44 SLC2A1 Zornitza Stark Publications for gene: SLC2A1 were set to
Alternating Hemiplegia and Hemiplegic Migraine v0.43 SLC2A1 Zornitza Stark Mode of inheritance for gene: SLC2A1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Alternating Hemiplegia and Hemiplegic Migraine v0.42 SLC2A1 Zornitza Stark reviewed gene: SLC2A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25440161, 24824604, 20621801; Phenotypes: Hemiplegic migraine; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Alternating Hemiplegia and Hemiplegic Migraine v0.42 SLC1A3 Zornitza Stark Marked gene: SLC1A3 as ready
Alternating Hemiplegia and Hemiplegic Migraine v0.42 SLC1A3 Zornitza Stark Gene: slc1a3 has been classified as Amber List (Moderate Evidence).
Alternating Hemiplegia and Hemiplegic Migraine v0.42 SLC1A3 Zornitza Stark Phenotypes for gene: SLC1A3 were changed from to Hemiplegic migraine
Alternating Hemiplegia and Hemiplegic Migraine v0.41 SLC1A3 Zornitza Stark Publications for gene: SLC1A3 were set to
Alternating Hemiplegia and Hemiplegic Migraine v0.40 SLC1A3 Zornitza Stark Mode of inheritance for gene: SLC1A3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Alternating Hemiplegia and Hemiplegic Migraine v0.39 SLC1A3 Zornitza Stark Classified gene: SLC1A3 as Amber List (moderate evidence)
Alternating Hemiplegia and Hemiplegic Migraine v0.39 SLC1A3 Zornitza Stark Gene: slc1a3 has been classified as Amber List (Moderate Evidence).
Alternating Hemiplegia and Hemiplegic Migraine v0.38 SLC1A3 Zornitza Stark reviewed gene: SLC1A3: Rating: AMBER; Mode of pathogenicity: None; Publications: 32754645, 16116111; Phenotypes: Hemiplegic migraine; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4841 ATP1A4 Zornitza Stark Marked gene: ATP1A4 as ready
Mendeliome v0.4841 ATP1A4 Zornitza Stark Gene: atp1a4 has been classified as Red List (Low Evidence).
Mendeliome v0.4841 ATP1A4 Zornitza Stark gene: ATP1A4 was added
gene: ATP1A4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ATP1A4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP1A4 were set to 32549268
Phenotypes for gene: ATP1A4 were set to Hemiplegic migraine
Review for gene: ATP1A4 was set to RED
Added comment: Single family reported where missense variant segregated with hemiplegic migraine in four affected individuals.
Sources: Literature
Alternating Hemiplegia and Hemiplegic Migraine v0.38 ATP1A4 Zornitza Stark Marked gene: ATP1A4 as ready
Alternating Hemiplegia and Hemiplegic Migraine v0.38 ATP1A4 Zornitza Stark Gene: atp1a4 has been classified as Red List (Low Evidence).
Alternating Hemiplegia and Hemiplegic Migraine v0.38 ATP1A4 Zornitza Stark gene: ATP1A4 was added
gene: ATP1A4 was added to Alternating Hemiplegia and Hemiplegic Migraine. Sources: Literature
Mode of inheritance for gene: ATP1A4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP1A4 were set to 32549268
Phenotypes for gene: ATP1A4 were set to Hemiplegic migraine
Review for gene: ATP1A4 was set to RED
Added comment: Single family reported where missense variant segregated with hemiplegic migraine in four affected individuals.
Sources: Literature
Alternating Hemiplegia and Hemiplegic Migraine v0.37 SCN1A Zornitza Stark Marked gene: SCN1A as ready
Alternating Hemiplegia and Hemiplegic Migraine v0.37 SCN1A Zornitza Stark Gene: scn1a has been classified as Green List (High Evidence).
Alternating Hemiplegia and Hemiplegic Migraine v0.37 SCN1A Zornitza Stark Phenotypes for gene: SCN1A were changed from to Migraine, familial hemiplegic, 3, MIM# 609634
Alternating Hemiplegia and Hemiplegic Migraine v0.36 SCN1A Zornitza Stark Publications for gene: SCN1A were set to
Alternating Hemiplegia and Hemiplegic Migraine v0.35 SCN1A Zornitza Stark Mode of inheritance for gene: SCN1A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Alternating Hemiplegia and Hemiplegic Migraine v0.34 SCN1A Zornitza Stark reviewed gene: SCN1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 31904117, 30498473, 30038559, 29986598; Phenotypes: Migraine, familial hemiplegic, 3, MIM# 609634; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Alternating Hemiplegia and Hemiplegic Migraine v0.34 PNKD Zornitza Stark Marked gene: PNKD as ready
Alternating Hemiplegia and Hemiplegic Migraine v0.34 PNKD Zornitza Stark Gene: pnkd has been classified as Red List (Low Evidence).
Alternating Hemiplegia and Hemiplegic Migraine v0.34 PNKD Zornitza Stark Phenotypes for gene: PNKD were changed from to Paroxysmal nonkinesigenic dyskinesia 1, MIM# 118800
Alternating Hemiplegia and Hemiplegic Migraine v0.33 PNKD Zornitza Stark Mode of inheritance for gene: PNKD was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Alternating Hemiplegia and Hemiplegic Migraine v0.32 PNKD Zornitza Stark Classified gene: PNKD as Red List (low evidence)
Alternating Hemiplegia and Hemiplegic Migraine v0.32 PNKD Zornitza Stark Gene: pnkd has been classified as Red List (Low Evidence).
Alternating Hemiplegia and Hemiplegic Migraine v0.31 PNKD Zornitza Stark reviewed gene: PNKD: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Paroxysmal nonkinesigenic dyskinesia 1, MIM# 118800; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Alternating Hemiplegia and Hemiplegic Migraine v0.31 KCNK18 Zornitza Stark Marked gene: KCNK18 as ready
Alternating Hemiplegia and Hemiplegic Migraine v0.31 KCNK18 Zornitza Stark Gene: kcnk18 has been classified as Green List (High Evidence).
Alternating Hemiplegia and Hemiplegic Migraine v0.31 KCNK18 Zornitza Stark Phenotypes for gene: KCNK18 were changed from to {Migraine, with or without aura, susceptibility to, 13}, MIM# 613656
Alternating Hemiplegia and Hemiplegic Migraine v0.30 KCNK18 Zornitza Stark Publications for gene: KCNK18 were set to
Alternating Hemiplegia and Hemiplegic Migraine v0.29 KCNK18 Zornitza Stark Mode of inheritance for gene: KCNK18 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Alternating Hemiplegia and Hemiplegic Migraine v0.28 KCNK18 Zornitza Stark reviewed gene: KCNK18: Rating: GREEN; Mode of pathogenicity: None; Publications: 20871611, 32394190, 30573346, 23904616, 22355750; Phenotypes: {Migraine, with or without aura, susceptibility to, 13}, MIM# 613656; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Alternating Hemiplegia and Hemiplegic Migraine v0.27 KCNA1 Zornitza Stark Marked gene: KCNA1 as ready
Alternating Hemiplegia and Hemiplegic Migraine v0.27 KCNA1 Zornitza Stark Gene: kcna1 has been classified as Amber List (Moderate Evidence).
Alternating Hemiplegia and Hemiplegic Migraine v0.27 KCNA1 Zornitza Stark Phenotypes for gene: KCNA1 were changed from to Episodic ataxia/myokymia syndrome, MIM# 160120
Alternating Hemiplegia and Hemiplegic Migraine v0.26 KCNA1 Zornitza Stark Publications for gene: KCNA1 were set to
Alternating Hemiplegia and Hemiplegic Migraine v0.25 KCNA1 Zornitza Stark Mode of inheritance for gene: KCNA1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Alternating Hemiplegia and Hemiplegic Migraine v0.24 KCNA1 Zornitza Stark Classified gene: KCNA1 as Amber List (moderate evidence)
Alternating Hemiplegia and Hemiplegic Migraine v0.24 KCNA1 Zornitza Stark Gene: kcna1 has been classified as Amber List (Moderate Evidence).
Alternating Hemiplegia and Hemiplegic Migraine v0.23 KCNA1 Zornitza Stark reviewed gene: KCNA1: Rating: AMBER; Mode of pathogenicity: None; Publications: 25642194; Phenotypes: Episodic ataxia/myokymia syndrome, MIM# 160120; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Alternating Hemiplegia and Hemiplegic Migraine v0.23 CACNA1A Zornitza Stark Marked gene: CACNA1A as ready
Alternating Hemiplegia and Hemiplegic Migraine v0.23 CACNA1A Zornitza Stark Gene: cacna1a has been classified as Green List (High Evidence).
Alternating Hemiplegia and Hemiplegic Migraine v0.23 CACNA1A Zornitza Stark Phenotypes for gene: CACNA1A were changed from to Migraine, familial hemiplegic, 1, MIM# 141500
Alternating Hemiplegia and Hemiplegic Migraine v0.22 CACNA1A Zornitza Stark Mode of inheritance for gene: CACNA1A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Alternating Hemiplegia and Hemiplegic Migraine v0.21 CACNA1A Zornitza Stark reviewed gene: CACNA1A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Migraine, familial hemiplegic, 1, MIM# 141500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4840 BSND Zornitza Stark Marked gene: BSND as ready
Mendeliome v0.4840 BSND Zornitza Stark Gene: bsnd has been classified as Green List (High Evidence).
Mendeliome v0.4840 BSND Zornitza Stark Phenotypes for gene: BSND were changed from to Bartter syndrome, type 4a, MIM#602522
Mendeliome v0.4839 BSND Zornitza Stark Publications for gene: BSND were set to
Mendeliome v0.4838 BSND Zornitza Stark Mode of inheritance for gene: BSND was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4837 BSND Zornitza Stark changed review comment from: Some individuals with severe Bartter syndrome have been described as having intellectual disability, whereas others with milder symptoms have normal intellect.
Sources: Expert list; to: Well established gene-disease association.
Sources: Expert list
Mendeliome v0.4837 BSND Zornitza Stark edited their review of gene: BSND: Changed publications: 11687798, 12574213, 30174009, 21269598
Achromatopsia v1.0 Bryony Thompson promoted panel to version 1.0
Hyperthyroidism v0.18 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Rare Disease
Hyperthyroidism v0.17 TSHR Zornitza Stark Marked gene: TSHR as ready
Hyperthyroidism v0.17 TSHR Zornitza Stark Gene: tshr has been classified as Green List (High Evidence).
Hyperthyroidism v0.17 TSHR Zornitza Stark Phenotypes for gene: TSHR were changed from Hyperthyroidism, nonautoimmune, 609152; Congenital, nonautoimmune hyperthyroidism to Hyperthyroidism, nonautoimmune, MIM# 609152
Hyperthyroidism v0.16 TSHR Zornitza Stark Publications for gene: TSHR were set to
Hyperthyroidism v0.15 TSHR Zornitza Stark Mode of inheritance for gene: TSHR was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hyperthyroidism v0.14 TSHR Zornitza Stark reviewed gene: TSHR: Rating: GREEN; Mode of pathogenicity: None; Publications: 7920658, 7800007, 8964822; Phenotypes: Hyperthyroidism, nonautoimmune, MIM# 609152; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Additional findings_Paediatric v0.127 Zornitza Stark Panel name changed from Additional findings Paediatric to Additional findings_Paediatric
Additional findings_Paediatric v0.125 Zornitza Stark Panel name changed from Newborn Screening_BabySeq to Additional findings Paediatric
Panel types changed to Australian Genomics
Bardet Biedl syndrome v0.57 LZTFL1 Zornitza Stark Marked gene: LZTFL1 as ready
Bardet Biedl syndrome v0.57 LZTFL1 Zornitza Stark Gene: lztfl1 has been classified as Green List (High Evidence).
Bardet Biedl syndrome v0.57 LZTFL1 Zornitza Stark Phenotypes for gene: LZTFL1 were changed from to Bardet-Biedl syndrome 17 (MIM#615994)
Bardet Biedl syndrome v0.56 LZTFL1 Zornitza Stark Publications for gene: LZTFL1 were set to
Bardet Biedl syndrome v0.55 LZTFL1 Zornitza Stark Mode of inheritance for gene: LZTFL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Bardet Biedl syndrome v0.54 CEP290 Zornitza Stark Marked gene: CEP290 as ready
Bardet Biedl syndrome v0.54 CEP290 Zornitza Stark Gene: cep290 has been classified as Green List (High Evidence).
Bardet Biedl syndrome v0.54 CEP290 Zornitza Stark Phenotypes for gene: CEP290 were changed from to Bardet-Biedl syndrome 14, MIM# 615991
Bardet Biedl syndrome v0.53 CEP290 Zornitza Stark Publications for gene: CEP290 were set to 18327255; 20690115
Bardet Biedl syndrome v0.53 CEP290 Zornitza Stark Publications for gene: CEP290 were set to
Bardet Biedl syndrome v0.52 CEP290 Zornitza Stark Mode of inheritance for gene: CEP290 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Bardet Biedl syndrome v0.51 CEP290 Zornitza Stark reviewed gene: CEP290: Rating: GREEN; Mode of pathogenicity: None; Publications: 18327255, 20690115; Phenotypes: Bardet-Biedl syndrome 14, MIM# 615991; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Bardet Biedl syndrome v0.51 IFT172 Zornitza Stark changed review comment from: Three families reported with a BBS phenotype, although this association is not listed in OMIM. Gene is associated with other ciliopathies as well.; to: Three families reported with a BBS phenotype, although this association is not listed in OMIM or MONDO. Gene is associated with other ciliopathies as well.
Bardet Biedl syndrome v0.51 IFT172 Zornitza Stark reviewed gene: IFT172: Rating: GREEN; Mode of pathogenicity: None; Publications: 30761183, 26763875, 25168386; Phenotypes: Bardet-Biedl syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Bardet Biedl syndrome v0.51 BBS12 Zornitza Stark Marked gene: BBS12 as ready
Bardet Biedl syndrome v0.51 BBS12 Zornitza Stark Gene: bbs12 has been classified as Green List (High Evidence).
Bardet Biedl syndrome v0.51 BBS12 Zornitza Stark Phenotypes for gene: BBS12 were changed from to Bardet-Biedl syndrome 12, MIM# 615989
Bardet Biedl syndrome v0.50 BBS12 Zornitza Stark Publications for gene: BBS12 were set to
Bardet Biedl syndrome v0.49 BBS12 Zornitza Stark Mode of inheritance for gene: BBS12 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Bardet Biedl syndrome v0.48 BBS12 Zornitza Stark reviewed gene: BBS12: Rating: GREEN; Mode of pathogenicity: None; Publications: 19797195, 29633607, 26082521; Phenotypes: Bardet-Biedl syndrome 12, MIM# 615989; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Bardet Biedl syndrome v0.48 BBS10 Zornitza Stark Marked gene: BBS10 as ready
Bardet Biedl syndrome v0.48 BBS10 Zornitza Stark Gene: bbs10 has been classified as Green List (High Evidence).
Bardet Biedl syndrome v0.48 BBS10 Zornitza Stark Phenotypes for gene: BBS10 were changed from to Bardet-Biedl syndrome 10, MIM# 615987
Bardet Biedl syndrome v0.47 BBS10 Zornitza Stark Publications for gene: BBS10 were set to
Bardet Biedl syndrome v0.46 BBS10 Zornitza Stark Mode of inheritance for gene: BBS10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Bardet Biedl syndrome v0.45 BBS10 Zornitza Stark reviewed gene: BBS10: Rating: GREEN; Mode of pathogenicity: None; Publications: 16582908, 19252258; Phenotypes: Bardet-Biedl syndrome 10, MIM# 615987; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Bardet Biedl syndrome v0.45 SDCCAG8 Zornitza Stark Marked gene: SDCCAG8 as ready
Bardet Biedl syndrome v0.45 SDCCAG8 Zornitza Stark Gene: sdccag8 has been classified as Green List (High Evidence).
Bardet Biedl syndrome v0.45 SDCCAG8 Zornitza Stark Phenotypes for gene: SDCCAG8 were changed from to Bardet-Biedl syndrome 16, MIM# 615993
Bardet Biedl syndrome v0.44 SDCCAG8 Zornitza Stark Publications for gene: SDCCAG8 were set to
Bardet Biedl syndrome v0.43 SDCCAG8 Zornitza Stark Mode of inheritance for gene: SDCCAG8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Bardet Biedl syndrome v0.42 SDCCAG8 Zornitza Stark reviewed gene: SDCCAG8: Rating: GREEN; Mode of pathogenicity: None; Publications: 20835237, 22626039, 22626039; Phenotypes: Bardet-Biedl syndrome 16, MIM# 615993; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Bardet Biedl syndrome v0.42 TTC8 Zornitza Stark Marked gene: TTC8 as ready
Bardet Biedl syndrome v0.42 TTC8 Zornitza Stark Gene: ttc8 has been classified as Green List (High Evidence).
Bardet Biedl syndrome v0.42 TTC8 Zornitza Stark Phenotypes for gene: TTC8 were changed from to Bardet-Biedl syndrome 8, MIM# 615985
Bardet Biedl syndrome v0.41 TTC8 Zornitza Stark Publications for gene: TTC8 were set to
Bardet Biedl syndrome v0.40 TTC8 Zornitza Stark Mode of inheritance for gene: TTC8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Bardet Biedl syndrome v0.39 TTC8 Zornitza Stark reviewed gene: TTC8: Rating: GREEN; Mode of pathogenicity: None; Publications: 14520415, 19797195; Phenotypes: Bardet-Biedl syndrome 8, MIM# 615985; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Bardet Biedl syndrome v0.39 ALMS1 Zornitza Stark Marked gene: ALMS1 as ready
Bardet Biedl syndrome v0.39 ALMS1 Zornitza Stark Gene: alms1 has been classified as Green List (High Evidence).
Bardet Biedl syndrome v0.39 ALMS1 Zornitza Stark Phenotypes for gene: ALMS1 were changed from to Alstrom syndrome, MIM# 203800
Bardet Biedl syndrome v0.38 ALMS1 Zornitza Stark Mode of inheritance for gene: ALMS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Bardet Biedl syndrome v0.37 BBS1 Zornitza Stark Marked gene: BBS1 as ready
Bardet Biedl syndrome v0.37 BBS1 Zornitza Stark Gene: bbs1 has been classified as Green List (High Evidence).
Bardet Biedl syndrome v0.37 BBS1 Zornitza Stark Phenotypes for gene: BBS1 were changed from to Bardet-Biedl syndrome 1, MIM# 209900
Bardet Biedl syndrome v0.36 BBS1 Zornitza Stark Publications for gene: BBS1 were set to
Bardet Biedl syndrome v0.35 BBS1 Zornitza Stark Mode of inheritance for gene: BBS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Bardet Biedl syndrome v0.34 BBS1 Zornitza Stark reviewed gene: BBS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20177705; Phenotypes: Bardet-Biedl syndrome 1, MIM# 209900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Bardet Biedl syndrome v0.34 ARL6 Zornitza Stark Marked gene: ARL6 as ready
Bardet Biedl syndrome v0.34 ARL6 Zornitza Stark Gene: arl6 has been classified as Green List (High Evidence).
Bardet Biedl syndrome v0.34 ARL6 Zornitza Stark Phenotypes for gene: ARL6 were changed from to Bardet-Biedl syndrome 3, MIM# 600151
Bardet Biedl syndrome v0.33 ARL6 Zornitza Stark Publications for gene: ARL6 were set to
Bardet Biedl syndrome v0.32 ARL6 Zornitza Stark Mode of inheritance for gene: ARL6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Bardet Biedl syndrome v0.31 ARL6 Zornitza Stark reviewed gene: ARL6: Rating: GREEN; Mode of pathogenicity: None; Publications: 15258860, 32361989, 31888296, 25402481; Phenotypes: Bardet-Biedl syndrome 3, MIM# 600151; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Aortopathy_Connective Tissue Disorders v1.0 Zornitza Stark promoted panel to version 1.0
Craniosynostosis v1.0 Zornitza Stark promoted panel to version 1.0
Glaucoma congenital v1.0 Zornitza Stark promoted panel to version 1.0
Glaucoma congenital v0.63 PITX2 Zornitza Stark Marked gene: PITX2 as ready
Glaucoma congenital v0.63 PITX2 Zornitza Stark Gene: pitx2 has been classified as Green List (High Evidence).
Glaucoma congenital v0.63 PITX2 Zornitza Stark Phenotypes for gene: PITX2 were changed from to Axenfeld-Rieger syndrome, type 1, MIM# 180500
Glaucoma congenital v0.62 PITX2 Zornitza Stark Publications for gene: PITX2 were set to
Glaucoma congenital v0.61 PITX2 Zornitza Stark Mode of inheritance for gene: PITX2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Glaucoma congenital v0.60 PITX2 Zornitza Stark reviewed gene: PITX2: Rating: GREEN; Mode of pathogenicity: None; Publications: 8944018, 31185933, 29023440; Phenotypes: Axenfeld-Rieger syndrome, type 1, MIM# 180500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Glaucoma congenital v0.60 MYOC Zornitza Stark Marked gene: MYOC as ready
Glaucoma congenital v0.60 MYOC Zornitza Stark Gene: myoc has been classified as Green List (High Evidence).
Glaucoma congenital v0.60 MYOC Zornitza Stark Phenotypes for gene: MYOC were changed from to Glaucoma 1A, primary open angle, MIM# 137750
Glaucoma congenital v0.59 MYOC Zornitza Stark Publications for gene: MYOC were set to
Glaucoma congenital v0.58 MYOC Zornitza Stark Mode of inheritance for gene: MYOC was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Glaucoma congenital v0.57 MYOC Zornitza Stark reviewed gene: MYOC: Rating: GREEN; Mode of pathogenicity: None; Publications: 9535666; Phenotypes: Glaucoma 1A, primary open angle, MIM# 137750; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4837 LTBP2 Zornitza Stark Marked gene: LTBP2 as ready
Mendeliome v0.4837 LTBP2 Zornitza Stark Gene: ltbp2 has been classified as Green List (High Evidence).
Mendeliome v0.4837 LTBP2 Zornitza Stark Phenotypes for gene: LTBP2 were changed from to Glaucoma 3, primary congenital, D 613086; Microspherophakia and/or megalocornea, with ectopia lentis and with or without secondary glaucoma, MIM# 251750
Mendeliome v0.4836 LTBP2 Zornitza Stark Publications for gene: LTBP2 were set to
Mendeliome v0.4835 LTBP2 Zornitza Stark Mode of inheritance for gene: LTBP2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4834 LTBP2 Zornitza Stark reviewed gene: LTBP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 19656777, 19361779, 20617341, 32165823, 30380740, 30565850; Phenotypes: Glaucoma 3, primary congenital, D 613086, Microspherophakia and/or megalocornea, with ectopia lentis and with or without secondary glaucoma, MIM# 251750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Glaucoma congenital v0.57 LTBP2 Zornitza Stark edited their review of gene: LTBP2: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Glaucoma congenital v0.57 LTBP2 Zornitza Stark Marked gene: LTBP2 as ready
Glaucoma congenital v0.57 LTBP2 Zornitza Stark Gene: ltbp2 has been classified as Green List (High Evidence).
Glaucoma congenital v0.57 LTBP2 Zornitza Stark Phenotypes for gene: LTBP2 were changed from to Glaucoma 3, primary congenital, D 613086; Microspherophakia and/or megalocornea, with ectopia lentis and with or without secondary glaucoma, MIM# 251750
Glaucoma congenital v0.56 LTBP2 Zornitza Stark Publications for gene: LTBP2 were set to
Glaucoma congenital v0.55 LTBP2 Zornitza Stark Mode of inheritance for gene: LTBP2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Glaucoma congenital v0.54 LTBP2 Zornitza Stark edited their review of gene: LTBP2: Changed rating: GREEN
Glaucoma congenital v0.54 LTBP2 Zornitza Stark reviewed gene: LTBP2: Rating: ; Mode of pathogenicity: None; Publications: 19656777, 19361779, 20617341, 32165823, 30380740, 30565850; Phenotypes: Glaucoma 3, primary congenital, D 613086, Microspherophakia and/or megalocornea, with ectopia lentis and with or without secondary glaucoma, MIM# 251750; Mode of inheritance: None
Glaucoma congenital v0.54 LMX1B Zornitza Stark Marked gene: LMX1B as ready
Glaucoma congenital v0.54 LMX1B Zornitza Stark Gene: lmx1b has been classified as Green List (High Evidence).
Glaucoma congenital v0.54 LMX1B Zornitza Stark Phenotypes for gene: LMX1B were changed from to Nail-patella syndrome, MIM# 161200
Glaucoma congenital v0.53 LMX1B Zornitza Stark Mode of inheritance for gene: LMX1B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Glaucoma congenital v0.52 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
Glaucoma congenital v0.52 FOXC1 Zornitza Stark Marked gene: FOXC1 as ready
Glaucoma congenital v0.52 FOXC1 Zornitza Stark Gene: foxc1 has been classified as Green List (High Evidence).
Glaucoma congenital v0.52 FOXC1 Zornitza Stark Phenotypes for gene: FOXC1 were changed from to Axenfeld-Rieger syndrome, type 3, MIM# 602482
Glaucoma congenital v0.51 FOXC1 Zornitza Stark Mode of inheritance for gene: FOXC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Glaucoma congenital v0.50 FOXC1 Zornitza Stark reviewed gene: FOXC1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Axenfeld-Rieger syndrome, type 3, MIM# 602482; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4834 CYP1B1 Zornitza Stark Publications for gene: CYP1B1 were set to 21730847; 27243976
Mendeliome v0.4833 CYP1B1 Zornitza Stark reviewed gene: CYP1B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 9463332, 10655546, 12372064, 21081970; Phenotypes: Glaucoma 3A, primary open angle, congenital, juvenile, or adult onset, MIM# 231300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Glaucoma congenital v0.50 CYP1B1 Zornitza Stark Marked gene: CYP1B1 as ready
Glaucoma congenital v0.50 CYP1B1 Zornitza Stark Gene: cyp1b1 has been classified as Green List (High Evidence).
Glaucoma congenital v0.50 CYP1B1 Zornitza Stark Phenotypes for gene: CYP1B1 were changed from to Glaucoma 3A, primary open angle, congenital, juvenile, or adult onset, MIM# 231300
Glaucoma congenital v0.49 CYP1B1 Zornitza Stark Publications for gene: CYP1B1 were set to
Glaucoma congenital v0.48 CYP1B1 Zornitza Stark Mode of inheritance for gene: CYP1B1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Glaucoma congenital v0.47 CYP1B1 Zornitza Stark reviewed gene: CYP1B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 9463332, 10655546, 12372064, 21081970; Phenotypes: Glaucoma 3A, primary open angle, congenital, juvenile, or adult onset, MIM# 231300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v1.0 Zornitza Stark promoted panel to version 1.0
Rhabdomyolysis and Metabolic Myopathy v0.81 SCN4A Zornitza Stark Marked gene: SCN4A as ready
Rhabdomyolysis and Metabolic Myopathy v0.81 SCN4A Zornitza Stark Gene: scn4a has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.81 SCN4A Zornitza Stark Publications for gene: SCN4A were set to
Rhabdomyolysis and Metabolic Myopathy v0.80 SCN4A Zornitza Stark reviewed gene: SCN4A: Rating: GREEN; Mode of pathogenicity: None; Publications: 23801527, 28779239, 32978841; Phenotypes: SCN4A-related muscle disorders; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rhabdomyolysis and Metabolic Myopathy v0.80 Zornitza Stark Panel name changed from Rhabdomyolysis RMH to Rhabdomyolysis
Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Rhabdomyolysis and Metabolic Myopathy v0.79 ACAD9 Zornitza Stark Marked gene: ACAD9 as ready
Rhabdomyolysis and Metabolic Myopathy v0.79 ACAD9 Zornitza Stark Gene: acad9 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.79 ACAD9 Zornitza Stark Publications for gene: ACAD9 were set to
Rhabdomyolysis and Metabolic Myopathy v0.78 ACADVL Zornitza Stark Marked gene: ACADVL as ready
Rhabdomyolysis and Metabolic Myopathy v0.78 ACADVL Zornitza Stark Gene: acadvl has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.78 ACADVL Zornitza Stark Publications for gene: ACADVL were set to
Rhabdomyolysis and Metabolic Myopathy v0.77 ALDOA Zornitza Stark Marked gene: ALDOA as ready
Rhabdomyolysis and Metabolic Myopathy v0.77 ALDOA Zornitza Stark Gene: aldoa has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.77 ALDOA Zornitza Stark Publications for gene: ALDOA were set to
Rhabdomyolysis and Metabolic Myopathy v0.76 ENO3 Zornitza Stark Marked gene: ENO3 as ready
Rhabdomyolysis and Metabolic Myopathy v0.76 ENO3 Zornitza Stark Gene: eno3 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.76 ENO3 Zornitza Stark Phenotypes for gene: ENO3 were changed from ?Glycogen storage disease XIII 612932 to Glycogen storage disease XIII 612932
Rhabdomyolysis and Metabolic Myopathy v0.75 ENO3 Zornitza Stark Publications for gene: ENO3 were set to
Rhabdomyolysis and Metabolic Myopathy v0.74 ETFA Zornitza Stark Marked gene: ETFA as ready
Rhabdomyolysis and Metabolic Myopathy v0.74 ETFA Zornitza Stark Gene: etfa has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.74 ETFA Zornitza Stark Publications for gene: ETFA were set to
Rhabdomyolysis and Metabolic Myopathy v0.73 ETFDH Zornitza Stark Marked gene: ETFDH as ready