| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Early onset or syndromic epilepsy v1.191 | KCNK4 | Rebecca Foulger Source Wessex and West Midlands GLH was added to KCNK4. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.190 | KCNK4 | Rebecca Foulger Source NHS GMS was added to KCNK4. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.189 | KCNK4 | Rebecca Foulger reviewed gene: KCNK4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.188 | KCNK4 | Tracy Lester reviewed gene: KCNK4: Rating: GREEN; Mode of pathogenicity: ; Publications: 30290154; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v0.510 | KCNK4 | Louise Daugherty Classified gene: KCNK4 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v0.510 | KCNK4 | Louise Daugherty Added comment: Comment on list classification: Based on evidence in the literature and from external review, Sarah Leigh on 16 Oct 2018 classified gene: KCNK4 as Green List (high evidence) on Genetic Epilepsy Syndromes panel v0.504. However, due to a data outage in PanelApp at the time the rating of this particular gene on this panel was not updated eg: the rating of a gene was changed, but was not reflected in production however action was logged in the activity. Issue has now been solved so the rating of this gene is now being changed to Green as it will now be reflected in production to represent the required update | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v0.510 | KCNK4 | Louise Daugherty Gene: kcnk4 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v0.504 | KCNK4 | Sarah Leigh Classified gene: KCNK4 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v0.504 | KCNK4 | Sarah Leigh Gene: kcnk4 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v0.503 | KCNK4 |
Konstantinos Varvagiannis gene: KCNK4 was added gene: KCNK4 was added to Genetic Epilepsy Syndromes. Sources: Expert Review,Literature Mode of inheritance for gene: KCNK4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: KCNK4 were set to 30290154 Phenotypes for gene: KCNK4 were set to Neurodevelopmental delay; Intellectual disability; Seizures; Gingival overgrowth; Hypertrichosis Penetrance for gene: KCNK4 were set to unknown Mode of pathogenicity for gene: KCNK4 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: KCNK4 was set to AMBER Added comment: PMID: 30290154 reports on 3 unrelated individuals with de novo missense KCNK4 variants. All three individuals presented with developmental delay and epilepsy. Severe intellectual disability was a feature in two of these individuals while the third displayed low average intellectual functioning (IQ of 85). Other features common in all included facial dysmorphism (bushy eyebrows, long eyelashes, thin everted upper lip, micrognathia), generalized hypertrichosis and gingival overgrowth. The two missense variants reported [(p.Ala172Glu) and (p.Ala244Pro)] occurred as de novo events in all subjects, while the first SNV was observed in 2 (of the 3) patients with severe intellectual disability. Functional studies were suggestive of a gain-of-function effect. In line with this mechanism, Kcnk4 knockout mice did not seem to exhibit seizures, deficits in cognition or other neurodevelopmental phenotypes in a study conducted earlier and cited by the authors (PMID: 15175651). As a result this gene can be considered for inclusion in the panel as amber (or green). Sources: Expert Review, Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||