NM_172107.4(KCNQ2):c.380A>G (p.Tyr127Cys) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Nov 14, 2019
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:: RCV001232372.9

Allele description [Variation Report for NM_172107.4(KCNQ2):c.380A>G (p.Tyr127Cys)]

NM_172107.4(KCNQ2):c.380A>G (p.Tyr127Cys)

Gene:

KCNQ2:potassium voltage-gated channel subfamily Q member 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

20q13.33

Genomic location:

Preferred name:

NM_172107.4(KCNQ2):c.380A>G (p.Tyr127Cys)

Other names:

p.Y127C:TAC>TGC

HGVS:

NC_000020.11:g.63446754T>C
NG_009004.2:g.30887A>G
NM_004518.6:c.380A>G
NM_172106.3:c.380A>G
NM_172107.4:c.380A>GMANE SELECT
NM_172108.5:c.380A>G
NM_172109.3:c.380A>G
NP_004509.2:p.Tyr127Cys
NP_742104.1:p.Tyr127Cys
NP_742105.1:p.Tyr127Cys
NP_742106.1:p.Tyr127Cys
NP_742107.1:p.Tyr127Cys
NC_000020.10:g.62078107T>C
NM_172107.2:c.380A>G
NM_172107.3:c.380A>G

Protein change:

Y127C

Links:

dbSNP: rs796052617

NCBI 1000 Genomes Browser:

rs796052617

Molecular consequence:

NM_004518.6:c.380A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_172106.3:c.380A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_172107.4:c.380A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_172108.5:c.380A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_172109.3:c.380A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Early infantile epileptic encephalopathy with suppression bursts (EIEE)
Synonyms:: Early infantile epileptic encephalopathy; Ohtahara syndrome; Developmental and epileptic encephalopathy
Identifiers:: MONDO: MONDO:0100062; MedGen: C0393706; Orphanet: 1934; OMIM: PS308350

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001404928	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Nov 14, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001404928

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Nov 14, 2019)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

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, SCV001404928.5

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

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has been observed in individual(s) with infantile onset epilepsy (Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 205863). This variant is not present in population databases (ExAC no frequency). This sequence change replaces tyrosine with cysteine at codon 127 of the KCNQ2 protein (p.Tyr127Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine.

#	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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