NM_172107.4(KCNQ2):c.365C>T (p.Ser122Leu) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Feb 16, 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:: RCV000187851.9

Allele description [Variation Report for NM_172107.4(KCNQ2):c.365C>T (p.Ser122Leu)]

NM_172107.4(KCNQ2):c.365C>T (p.Ser122Leu)

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.365C>T (p.Ser122Leu)

Other names:

p.S122L:TCG>TTG

HGVS:

NC_000020.11:g.63446769G>A
NG_009004.2:g.30872C>T
NM_004518.6:c.365C>T
NM_172106.3:c.365C>T
NM_172107.4:c.365C>TMANE SELECT
NM_172108.5:c.365C>T
NM_172109.3:c.365C>T
NP_004509.2:p.Ser122Leu
NP_742104.1:p.Ser122Leu
NP_742105.1:p.Ser122Leu
NP_742106.1:p.Ser122Leu
NP_742107.1:p.Ser122Leu
NC_000020.10:g.62078122G>A
NM_172107.2:c.365C>T
NM_172107.3:c.365C>T

Protein change:

S122L

Links:

dbSNP: rs118192194

NCBI 1000 Genomes Browser:

rs118192194

Molecular consequence:

NM_004518.6:c.365C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_172106.3:c.365C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_172107.4:c.365C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_172108.5:c.365C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_172109.3:c.365C>T - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000241451	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Feb 16, 2022)	germline	clinical testing	Citation Link,
SCV001808441	Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV001932516	Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000241451

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Feb 16, 2022)

germline

clinical testing

Citation Link,

SCV001808441

Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus

no assertion criteria provided

Pathogenic

germline

clinical testing

SCV001932516

Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus

See additional submitters

no assertion criteria provided

Pathogenic

germline

clinical testing

Help

Summary from all submissions

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

Details of each submission

From GeneDx, SCV000241451.16

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

Description

Published functional studies demonstrate slowed activation kinetics of the voltage-gated channel (Hunter et al., 2006); Missense variants in this gene are often considered pathogenic (HGMD); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This substitution is predicted to be within the extracellular loop between the S1 and S2 transmembrane segments; This variant is associated with the following publications: (PMID: 33098118, 16916607, 18238816, 28074849, 28082013, 27602407, 18698150, 28488083, 26544041, 34070668, 34711204, 33659638)

#	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 Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus, SCV001808441.1

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

#	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 Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus, SCV001932516.1

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

#	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

Last Updated: May 19, 2024

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