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| Mendeliome v1.3762 | KCNQ3 |
Lucy Spencer changed review comment from: From ClinGen: Definitive for DOMINANT complex neurodevelopmental disorder MONDO:0100038, KCNQ3-related - 24 probands across 7 publications, mostly de novo variants. Mutations are clustered at p.Arg227 and p.Arg230, with a gain of function mechanism PMID: 24851285. Moderate for DOMINANT self-limited familial neonatal epilepsy (Seizures, benign neonatal, 2 (MIM#121201)) - 15 missense in 18 probands across 16 publications. Variants clustered in the pore region (S5, S6, and intervening loop) and result in loss of function of channel activity PMID: 24851285. Note- there are several NMD predicted variants in this gene with over 10 hets in gnomad. Limited for RECESSIVE genetic developmental and epileptic encephalopathy MONDO:0100062, KCNQ3-related - 1 individual and 1 family from 2 publications with homozygous frameshifts PMID: 29852413; 31440727. All have seizures, various brain MRI findings, developmental delay and intellectual disability. The family had 3 similarly affected siblings, all homozygous for an NMD frameshift. The unrelated patient had a mildly affected uncle with learning difficulties and transient neonatal seizures, he was not tested for the variant. A third recessive patient not reported by ClinGen PMID: 29383681: 7yo girl with seizures, severe neurological impairment, and developmental delay. Compound heterozygous for two missense variants Val359Leu and Asp542Asn. Patch clamp studies showed that expression of either variant alone did not affect current density, but co-expression of both variants lead to a significant current reduction.; to: From ClinGen: Definitive for DOMINANT complex neurodevelopmental disorder MONDO:0100038, KCNQ3-related - 24 probands across 7 publications, mostly de novo variants. Mutations are clustered at p.Arg227 and p.Arg230, with a gain of function mechanism PMID: 24851285. Moderate for DOMINANT self-limited familial neonatal epilepsy (Seizures, benign neonatal, 2 (MIM#121201)) - 15 missense in 18 probands across 16 publications. Variants clustered in the pore region (S5, S6, and intervening loop) and result in loss of function of channel activity PMID: 24851285. Note- there are several NMD predicted variants in this gene with over 10 hets in gnomad. Limited for RECESSIVE genetic developmental and epileptic encephalopathy MONDO:0100062, KCNQ3-related - 1 individual and 1 family from 2 publications with homozygous frameshifts PMID: 29852413; 31440727. All have seizures, various brain MRI findings, developmental delay and intellectual disability. The family had 3 similarly affected siblings, all homozygous for an NMD frameshift. The unrelated patient had a mildly affected uncle with learning difficulties and transient neonatal seizures, he was not tested for the variant. A third recessive patient not reported by ClinGen PMID: 29383681: 7yo girl with seizures, severe neurological impairment, and developmental delay. Compound heterozygous for two missense variants Val359Leu and Asp542Asn. Patch clamp studies showed that expression of either variant alone did not affect current density, but co-expression of both variants lead to a significant current reduction. borderline amber/green for recessive |
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| Mendeliome v1.3762 | KCNQ3 | Lucy Spencer Mode of inheritance for gene: KCNQ3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3761 | KCNQ3 | Lucy Spencer Publications for gene: KCNQ3 were set to 33337327 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3760 | KCNQ3 | Lucy Spencer Phenotypes for gene: KCNQ3 were changed from Seizures, benign neonatal, 2, MIM# 121201 to Complex neurodevelopmental disorder MONDO:0100038, KCNQ3-related; Seizures, benign neonatal, 2 MIM#121201; genetic developmental and epileptic encephalopathy MONDO:0100062, KCNQ3-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3759 | KCNQ3 | Lucy Spencer reviewed gene: KCNQ3: Rating: GREEN; Mode of pathogenicity: None; Publications: 24851285, 29852413, 31440727; Phenotypes: Complex neurodevelopmental disorder MONDO:0100038, KCNQ3-related, Seizures, benign neonatal, 2 MIM#121201, genetic developmental and epileptic encephalopathy MONDO:0100062, KCNQ3-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5869 | KCNQ3 | Zornitza Stark Marked gene: KCNQ3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5869 | KCNQ3 | Zornitza Stark Gene: kcnq3 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5869 | KCNQ3 | Zornitza Stark Phenotypes for gene: KCNQ3 were changed from to Seizures, benign neonatal, 2, MIM# 121201 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5868 | KCNQ3 | Zornitza Stark Publications for gene: KCNQ3 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5867 | KCNQ3 | Zornitza Stark Mode of inheritance for gene: KCNQ3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5866 | KCNQ3 | Zornitza Stark reviewed gene: KCNQ3: Rating: GREEN; Mode of pathogenicity: None; Publications: 33337327; Phenotypes: Seizures, benign neonatal, 2, MIM# 121201; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.0 | KCNQ3 |
Zornitza Stark gene: KCNQ3 was added gene: KCNQ3 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: KCNQ3 was set to Unknown |
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