| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Intellectual disability - microarray and sequencing v2.1116 | KCNT2 | Ivone Leong Classified gene: KCNT2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.1116 | KCNT2 | Ivone Leong Added comment: Comment on list classification: New gene submitted by expert reviewer. Based on the evidence provided it was decided that there is enough evidence for this gene to be given Green status. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.1116 | KCNT2 | Ivone Leong Gene: kcnt2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.1115 | KCNT2 | Ivone Leong Added comment: Comment on mode of pathogenicity: Variants have gain-of-function effect. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.1115 | KCNT2 | Ivone Leong Mode of pathogenicity for gene: KCNT2 was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.1114 | KCNT2 | Ivone Leong Phenotypes for gene: KCNT2 were changed from ?Epileptic encephalopathy, early infantile 57, MIM 617771 to ?Epileptic encephalopathy, early infantile 57, 617771 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.1098 | KCNT2 |
Konstantinos Varvagiannis gene: KCNT2 was added gene: KCNT2 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: KCNT2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: KCNT2 were set to 29069600; 29740868 Phenotypes for gene: KCNT2 were set to ?Epileptic encephalopathy, early infantile 57, MIM 617771 Penetrance for gene: KCNT2 were set to unknown Review for gene: KCNT2 was set to GREEN Added comment: Heterozygous pathogenic KCNT2 variants cause ?Epileptic encephalopathy, early infantile, 57 (MIM 617771). At least 3 unrelated affected individuals have been reported : - PMID: 29069600 - Gururaj et al. 2017 : a male child with EOEE (hypotonia, profound DD and intractable infantile seizures) due to a de novo KCNT2 missense variant (NM_001287819.1:c.720T>A or p.Phe240Leu) identified by exome sequencing. - PMID: 29740868 - Ambrosino et al. 2018 : A girl with phenotype corresponding to West syndrome later evolving to Lennox-Gastaut syndrome. At the age of 9 years the girl displayed severe ID. Trio exome sequencing revealed a de novo missense KCNT2 variant (NM_001287820.2:c.569G>A or p.Arg190His). A 14 y.o. female recruited through the DDD study with phenotype corresponding to epilepsy of infancy with migrating focal seizures. The girl had poor language development and severe learning disability. Infective and metabolic causes were initially ruled out. Trio exome sequencing revealed a de novo missense SNV (c.569G>C or Arg190Pro). Overall KCNT2 has been commented to contribute to a phenotypic spectrum similar and overlapping to that of KCNT1 (Ambrosino et al.). [KCNT1 is rated green in both epilepsy and ID panels]. KCNT2 was recently included in the epilepsy panel as green (functional studies summarized in the respective reviews). The gene was also recently added to G2P, associated with 'Developmental and infantile epileptic encephalopathy'. It is not commonly included in gene panels for ID offered by diagnostic laboratories. As a result, KCNT2 could be considered for inclusion in the ID panel with green (or amber) rating. Sources: Literature |
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