Activity
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| Severe microcephaly v8.39 | TYW1 | Ida Ertmanska changed review comment from: Comment on list classification: There are 2 sibs reported in literature with a biallelic TYW1 variant and severe microcephaly (more than -3 SD). Based on available evidence, this gene can only be rated Red on this panel.; to: Comment on list classification: There are 2 sibs reported in literature with a biallelic TYW1 variant and severe microcephaly (more than -3 SD). Mouse and zebrafish knockout models showed microcephaly, supportive of the disease association. Based on available evidence, this gene can only be rated Amber on this panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v8.39 | TYW1 | Ida Ertmanska Classified gene: TYW1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v8.39 | TYW1 | Ida Ertmanska Gene: tyw1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v8.38 | TYW1 |
Ida Ertmanska changed review comment from: PMID: 34077496 Li et al., 2021 2 Chinese sibs (non-consanguineous parents) reported with comp het TYW1 variants: NM_018264: c.616C>T, p.R206C & c.1166G>A, p. R389Q. Proband CP_012_1, male - Wechsler Preschool and Primary Scale of Intelligence IQ = 40 at 7 years old (moderate ID); head circumference at 6yrs: 47.5 cm (−3.26 SD). CP_012_2, older sister - diagnosed with mixed type cerebral palsy (spasticity, dyskinesia), IQ <50 (moderate ID). Head circumference was 49 cm at 14yrs (−3.64 SD). Parents confirmed heterozygous for 1 variant each. TYW1:c.616C>T - MAF in gnomADv4 = 0.0004900, including 1 homozygote. TYW1:c.1166G>A MAF in gnomAD v4 = 0.0001559, no homozygotes. Functional evidence: TYW1 protein levels dramatically reduced in proband compared to controls; tyw1 deficiency in zebrafish resulted in ectopic neuronal cell migration in the brain and undifferentiated motor neuronal cells in the spinal cord - this was rescued by WT human and zebrafish tyw1 mRNA, but not by mRNA with patients' mutations. In addition, tyw1 knockdown zebrafish showed recuded swimming capacity. Kncokout tyw1-/- mice showed impaired motor function and reduced cognition in behavioural tests. PMID: 38706838 Sun et al., 2024 Fucntional evidence: Study used brain organoid model and human embryonic stem cells to show that translation efficiency of UUU codon was compromised in TYW1−/− cells. Also, neuron differentiation was impaired when TYW1 was depleted. TYW1 is not yet associated with a phenotype in OMIM, ClinGen or G2P (accessed 17 Mar 2026). Sources: Literature; to: PMID: 34077496 Li et al., 2021 2 Chinese sibs (non-consanguineous parents) reported with comp het TYW1 variants: NM_018264: c.616C>T, p.R206C & c.1166G>A, p. R389Q. Proband CP_012_1, male - Wechsler Preschool and Primary Scale of Intelligence IQ = 40 at 7 years old (moderate ID); head circumference at 6yrs: 47.5 cm (−3.26 SD). CP_012_2, older sister - diagnosed with mixed type cerebral palsy (spasticity, dyskinesia), IQ <50 (moderate ID). Head circumference was 49 cm at 14yrs (−3.64 SD). Parents confirmed heterozygous for 1 variant each. TYW1:c.616C>T - MAF in gnomADv4 = 0.0004900, including 1 homozygote. TYW1:c.1166G>A MAF in gnomAD v4 = 0.0001559, no homozygotes. Functional evidence: TYW1 protein levels dramatically reduced in proband compared to controls; tyw1 deficiency in zebrafish resulted in ectopic neuronal cell migration in the brain and undifferentiated motor neuronal cells in the spinal cord - this was rescued by WT human and zebrafish tyw1 mRNA, but not by mRNA with patients' mutations. In addition, tyw1 knockdown zebrafish showed recuded swimming capacity. Kncokout tyw1-/- mice showed impaired motor function and reduced cognition in behavioural tests. Microcephaly and neurological manifestation were observed in both mice and zebrafish. PMID: 38706838 Sun et al., 2024 Fucntional evidence: Study used brain organoid model and human embryonic stem cells to show that translation efficiency of UUU codon was compromised in TYW1−/− cells. Also, neuron differentiation was impaired when TYW1 was depleted. TYW1 is not yet associated with a phenotype in OMIM, ClinGen or G2P (accessed 17 Mar 2026). Sources: Literature |
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| Severe microcephaly v8.38 | TYW1 | Ida Ertmanska changed review comment from: Comment on list classification: There are 2 sibs reported in literature with a biallelic TYW1 variant and severe microcephaly (more than -3 SD). Based on available evidence, this gene can only be rated Red.; to: Comment on list classification: There are 2 sibs reported in literature with a biallelic TYW1 variant and severe microcephaly (more than -3 SD). Based on available evidence, this gene can only be rated Red on this panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v8.38 | TYW1 | Ida Ertmanska Tag watchlist was removed from gene: TYW1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v8.38 | TYW1 | Ida Ertmanska Classified gene: TYW1 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v8.38 | TYW1 | Ida Ertmanska Added comment: Comment on list classification: There are 2 sibs reported in literature with a biallelic TYW1 variant and severe microcephaly (more than -3 SD). Based on available evidence, this gene can only be rated Red. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v8.38 | TYW1 | Ida Ertmanska Gene: tyw1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v8.37 | TYW1 |
Ida Ertmanska gene: TYW1 was added gene: TYW1 was added to Severe microcephaly. Sources: Literature watchlist tags were added to gene: TYW1. Mode of inheritance for gene: TYW1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TYW1 were set to 34077496 Phenotypes for gene: TYW1 were set to cerebral palsy, MONDO:0006497; microcephaly, MONDO:0001149 Review for gene: TYW1 was set to AMBER Added comment: PMID: 34077496 Li et al., 2021 2 Chinese sibs (non-consanguineous parents) reported with comp het TYW1 variants: NM_018264: c.616C>T, p.R206C & c.1166G>A, p. R389Q. Proband CP_012_1, male - Wechsler Preschool and Primary Scale of Intelligence IQ = 40 at 7 years old (moderate ID); head circumference at 6yrs: 47.5 cm (−3.26 SD). CP_012_2, older sister - diagnosed with mixed type cerebral palsy (spasticity, dyskinesia), IQ <50 (moderate ID). Head circumference was 49 cm at 14yrs (−3.64 SD). Parents confirmed heterozygous for 1 variant each. TYW1:c.616C>T - MAF in gnomADv4 = 0.0004900, including 1 homozygote. TYW1:c.1166G>A MAF in gnomAD v4 = 0.0001559, no homozygotes. Functional evidence: TYW1 protein levels dramatically reduced in proband compared to controls; tyw1 deficiency in zebrafish resulted in ectopic neuronal cell migration in the brain and undifferentiated motor neuronal cells in the spinal cord - this was rescued by WT human and zebrafish tyw1 mRNA, but not by mRNA with patients' mutations. In addition, tyw1 knockdown zebrafish showed recuded swimming capacity. Kncokout tyw1-/- mice showed impaired motor function and reduced cognition in behavioural tests. PMID: 38706838 Sun et al., 2024 Fucntional evidence: Study used brain organoid model and human embryonic stem cells to show that translation efficiency of UUU codon was compromised in TYW1−/− cells. Also, neuron differentiation was impaired when TYW1 was depleted. TYW1 is not yet associated with a phenotype in OMIM, ClinGen or G2P (accessed 17 Mar 2026). Sources: Literature |
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