NM_004519.4(KCNQ3):c.1576C>T (p.Gln526Ter) AND Benign neonatal seizures

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 25, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003587134.3

Allele description [Variation Report for NM_004519.4(KCNQ3):c.1576C>T (p.Gln526Ter)]

NM_004519.4(KCNQ3):c.1576C>T (p.Gln526Ter)

Gene:

KCNQ3:potassium voltage-gated channel subfamily Q member 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8q24.22

Genomic location:

Preferred name:

NM_004519.4(KCNQ3):c.1576C>T (p.Gln526Ter)

HGVS:

NC_000008.11:g.132138009G>A
NG_008854.2:g.347749C>T
NM_001204824.2:c.1216C>T
NM_004519.4:c.1576C>TMANE SELECT
NP_001191753.1:p.Gln406Ter
NP_004510.1:p.Gln526Ter
NC_000008.10:g.133150256G>A

Protein change:

Q406*

Links:

dbSNP: rs2536875506

NCBI 1000 Genomes Browser:

rs2536875506

Molecular consequence:

NM_001204824.2:c.1216C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_004519.4:c.1576C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Benign neonatal seizures
Synonyms:: Benign familial neonatal seizures; Convulsions benign familial neonatal dominant form; Autosomal dominant form of benign neonatal seizures; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0016027; MedGen: C0220669; Orphanet: 1949; OMIM: PS121200

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004281164	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 25, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 29383681, 29852413, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004281164

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 25, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Kv7.3 Compound Heterozygous Variants in Early Onset Encephalopathy Reveal Additive Contribution of C-Terminal Residues to PIP(2)-Dependent K(+) Channel Gating.

Ambrosino P, Freri E, Castellotti B, Soldovieri MV, Mosca I, Manocchio L, Gellera C, Canafoglia L, Franceschetti S, Salis B, Iraci N, Miceli F, Ragona F, Granata T, DiFrancesco JC, Taglialatela M.

Mol Neurobiol. 2018 Aug;55(8):7009-7024. doi: 10.1007/s12035-018-0883-5. Epub 2018 Jan 30.

PubMed [citation]

PMID:: 29383681

Diagnostic yield of targeted massively parallel sequencing in children with epileptic encephalopathy.

Kothur K, Holman K, Farnsworth E, Ho G, Lorentzos M, Troedson C, Gupta S, Webster R, Procopis PG, Menezes MP, Antony J, Ardern-Holmes S, Dale RC, Christodoulou J, Gill D, Bennetts B.

Seizure. 2018 Jul;59:132-140. doi: 10.1016/j.seizure.2018.05.005. Epub 2018 May 28.

PubMed [citation]

PMID:: 29852413

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004281164.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Gln526*) in the KCNQ3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in KCNQ3 are known to be pathogenic (PMID: 29383681, 29852413). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with KCNQ3-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 16, 2025

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