NM_172107.4(KCNQ2):c.1004C>T (p.Pro335Leu) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Dec 1, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000187889.12

Allele description [Variation Report for NM_172107.4(KCNQ2):c.1004C>T (p.Pro335Leu)]

NM_172107.4(KCNQ2):c.1004C>T (p.Pro335Leu)

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.1004C>T (p.Pro335Leu)

Other names:

p.P335L:CCG>CTG

HGVS:

NC_000020.11:g.63438644G>A
NG_009004.2:g.38997C>T
NM_004518.6:c.1004C>T
NM_172106.3:c.1004C>T
NM_172107.4:c.1004C>TMANE SELECT
NM_172108.5:c.1004C>T
NM_172109.3:c.1004C>T
NP_004509.2:p.Pro335Leu
NP_742104.1:p.Pro335Leu
NP_742105.1:p.Pro335Leu
NP_742106.1:p.Pro335Leu
NP_742107.1:p.Pro335Leu
NC_000020.10:g.62069997G>A
NM_172107.2:c.1004C>T

Protein change:

P335L

Links:

dbSNP: rs796052641

NCBI 1000 Genomes Browser:

rs796052641

Molecular consequence:

NM_004518.6:c.1004C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_172106.3:c.1004C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_172107.4:c.1004C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_172108.5:c.1004C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_172109.3:c.1004C>T - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

Severe decrease in peak current [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0087]
Severe hyperpolarizing shift of voltage dependence of activation [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0031]
Severe slowing of activation [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0015]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000241491	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Dec 1, 2023)	germline	clinical testing	Citation Link,
SCV001430901	Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jul 22, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002023230	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 14, 2020)	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

SCV000241491

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Dec 1, 2023)

germline

clinical testing

Citation Link,

SCV001430901

Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jul 22, 2020)

germline

clinical testing

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

SCV002023230

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Sep 14, 2020)

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
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From GeneDx, SCV000241491.13

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

Description

In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); Missense variants in this gene are often considered pathogenic (HGMD); This variant is associated with the following publications: (PMID: 28191890, 28867141, 28135719, 25533962, 33754465, 31785789, 27602407, 35104249)

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

From Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center, SCV001430901.1

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

Description

PS2_VeryStrong, PM5_Supporting, PP2, PP3, PM1, PM2, PS4_Moderate

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

From Revvity Omics, Revvity, SCV002023230.3

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

#	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: Oct 8, 2024

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