NM_004519.4(KCNQ3):c.917C>T (p.Ala306Val) AND Benign neonatal seizures

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 12, 2022
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:: RCV001852468.6

Allele description [Variation Report for NM_004519.4(KCNQ3):c.917C>T (p.Ala306Val)]

NM_004519.4(KCNQ3):c.917C>T (p.Ala306Val)

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.917C>T (p.Ala306Val)

Other names:

p.A306V:GCC>GTC

HGVS:

NC_000008.11:g.132175469G>A
NG_008854.2:g.310289C>T
NM_001204824.2:c.557C>T
NM_004519.4:c.917C>TMANE SELECT
NP_001191753.1:p.Ala186Val
NP_001191753.1:p.Ala186Val
NP_004510.1:p.Ala306Val
NC_000008.10:g.133187716G>A
NM_001204824.1:c.557C>T
NM_004519.2:c.917C>T

Protein change:

A186V

Links:

dbSNP: rs796052678

NCBI 1000 Genomes Browser:

rs796052678

Molecular consequence:

NM_001204824.2:c.557C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_004519.4:c.917C>T - missense variant - [Sequence Ontology: SO:0001583]

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
SCV002190716	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 12, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29655203, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002190716

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 12, 2022)

germline

clinical testing

PubMed (2)
[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

Diagnostic outcomes for genetic testing of 70 genes in 8565 patients with epilepsy and neurodevelopmental disorders.

Lindy AS, Stosser MB, Butler E, Downtain-Pickersgill C, Shanmugham A, Retterer K, Brandt T, Richard G, McKnight DA.

Epilepsia. 2018 May;59(5):1062-1071. doi: 10.1111/epi.14074. Epub 2018 Apr 14.

PubMed [citation]

PMID:: 29655203

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002190716.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 306 of the KCNQ3 protein (p.Ala306Val). For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt KCNQ3 protein function. ClinVar contains an entry for this variant (Variation ID: 205966). This missense change has been observed in individual(s) with clinical features of KCNQ3-related conditions (PMID: 29655203; Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency).

#	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: Sep 29, 2024

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