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| Holoprosencephaly and septo-optic dysplasia v2.3 | CNOT1 |
chirag patel changed review comment from: Total of 7 unrelated individuals now reported with holoprosencephaly (6/7), pancreatic agenesis (4/7), and diabetes (5/7 - neonatal 4, adolescence 1). They all have the same rare heterozygous missense variant in CNOT1 (c.1603C>T, p.Arg535Cys). The variant was confirmed to be de novo in 5/7 families, as segregation could not be completed in 2 families. PMID 31006513: Knock‑in mouse model carrying CNOT1 p.Arg535Cys recapitulates holoprosencephaly, pancreatic agenesis and diabetes phenotypes, showing increased SHH expression, but rescue experiment not performed.; to: Total of 7 unrelated individuals now reported with holoprosencephaly (6/7), pancreatic agenesis (4/7), and diabetes (5/7 - neonatal 4, adolescence 1). They all have the same rare heterozygous missense variant in CNOT1 (c.1603C>T, p.Arg535Cys). The variant was confirmed to be de novo in 5/7 families, as segregation could not be completed in 2 families. PMID 31006513: Knock‑in mouse model carrying CNOT1 p.Arg535Cys recapitulates holoprosencephaly, pancreatic agenesis and diabetes phenotypes, showing increased SHH expression, but rescue experiment not performed. Any other variants need to be treated with extreme caution. |
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| Holoprosencephaly and septo-optic dysplasia v2.3 | CNOT1 | chirag patel Classified gene: CNOT1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Holoprosencephaly and septo-optic dysplasia v2.3 | CNOT1 | chirag patel Gene: cnot1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Holoprosencephaly and septo-optic dysplasia v2.2 | CNOT1 | chirag patel Publications for gene: CNOT1 were set to PMID: 31006513 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Holoprosencephaly and septo-optic dysplasia v2.1 | chirag patel Added reviews for gene CNOT1 from panel Monogenic Diabetes | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Holoprosencephaly and septo-optic dysplasia v2.0 | CNOT1 | Gene migrated from ENSG00000125107 to ENSG00000125107 (gene set migration) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Holoprosencephaly and septo-optic dysplasia v1.16 | CNOT1 | Zornitza Stark Phenotypes for gene: CNOT1 were changed from Holoprosencephaly 12 with or without pancreatic agenesis MONDO:0032787 to Holoprosencephaly 12 with or without pancreatic agenesis MONDO:0032787 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Holoprosencephaly and septo-optic dysplasia v1.16 | CNOT1 | Zornitza Stark Phenotypes for gene: CNOT1 were changed from HOLOPROSENCEPHALY 12 WITH OR WITHOUT PANCREATIC AGENESIS; HPE12; OMIM# 618500 to Holoprosencephaly 12 with or without pancreatic agenesis MONDO:0032787 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Holoprosencephaly and septo-optic dysplasia v1.15 | CNOT1 | Zornitza Stark Classified gene: CNOT1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Holoprosencephaly and septo-optic dysplasia v1.15 | CNOT1 | Zornitza Stark Gene: cnot1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Holoprosencephaly and septo-optic dysplasia v1.14 | CNOT1 | Zornitza Stark edited their review of gene: CNOT1: Changed rating: AMBER | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Holoprosencephaly and septo-optic dysplasia v1.14 | CNOT1 |
Zornitza Stark edited their review of gene: CNOT1: Added comment: LIMITED by ClinGen for holoprosencephaly 12 with or without pancreatic agenesis, MONDO:0032787 ClinGen curation: CNOT1 was originally reported in cases of holoprosencephaly and/or pancreatic agenesis/insufficiency in 2019 (PMID: 31006513, 31006510). One of the papers included 3 individuals with heterozygous p.Arg535Cys (PMID: 31006513), confirmed to be de novo in 2 individuals. One of these individuals was not scored due to a lack of documentation of holoprosencephaly. The other paper included 2 individuals with de novo p.Arg535Cys, both of whom with holoprosencephaly. A knock-in mouse model of this variant showed neurological and pancreatic abnormalities at E14.5, and this evidence was used to augment the genetic evidence. A mouse brain expression study (PMID: 31006510) was scored as functional evidence. In total, there is Limited evidence to support the gene-disease relationship between CNOT1 and holoprosencephaly with or without pancreatic agenesis. Of note, this gene has also been implicated in Vissers-Bodmer syndrome, which is characterized by global developmental delay and behavioral abnormalities apparent from infancy. As the condition is clinically distinct from holoprosencephaly and/or pancreatic agenesis/insufficiency, lacks specific structural brain anomalies, and likely has different molecular mechanisms, this will be/have been assessed separately.; Changed phenotypes: Holoprosencephaly 12 with or without pancreatic agenesis MONDO:0032787 |
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| Holoprosencephaly and septo-optic dysplasia v0.8 | CNOT1 | Alison Yeung Marked gene: CNOT1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Holoprosencephaly and septo-optic dysplasia v0.8 | CNOT1 | Alison Yeung Gene: cnot1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Holoprosencephaly and septo-optic dysplasia v0.8 | CNOT1 | Alison Yeung Classified gene: CNOT1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Holoprosencephaly and septo-optic dysplasia v0.8 | CNOT1 | Alison Yeung Gene: cnot1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Holoprosencephaly and septo-optic dysplasia v0.7 | CNOT1 |
Alison Yeung gene: CNOT1 was added gene: CNOT1 was added to Holoprosencephaly and septo-optic dysplasia. Sources: Literature Mode of inheritance for gene: CNOT1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: CNOT1 were set to PMID: 31006513 Phenotypes for gene: CNOT1 were set to HOLOPROSENCEPHALY 12 WITH OR WITHOUT PANCREATIC AGENESIS; HPE12; OMIM# 618500 Review for gene: CNOT1 was set to GREEN gene: CNOT1 was marked as current diagnostic Added comment: Three unrelated individuals reported. Functional studies in mouse Sources: Literature |
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