NM_000218.3(KCNQ1):c.644T>G (p.Val215Gly) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 7, 2024
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:: RCV004023761.1

Allele description [Variation Report for NM_000218.3(KCNQ1):c.644T>G (p.Val215Gly)]

NM_000218.3(KCNQ1):c.644T>G (p.Val215Gly)

Gene:

KCNQ1:potassium voltage-gated channel subfamily Q member 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11p15.5

Genomic location:

Preferred name:

NM_000218.3(KCNQ1):c.644T>G (p.Val215Gly)

HGVS:

NC_000011.10:g.2571364T>G
NG_008935.1:g.131374T>G
NM_000218.3:c.644T>GMANE SELECT
NM_001406836.1:c.644T>G
NM_001406837.1:c.374T>G
NM_181798.2:c.263T>G
NP_000209.2:p.Val215Gly
NP_000209.2:p.Val215Gly
NP_001393765.1:p.Val215Gly
NP_001393766.1:p.Val125Gly
NP_861463.1:p.Val88Gly
NP_861463.1:p.Val88Gly
LRG_287t1:c.644T>G
LRG_287t2:c.263T>G
LRG_287:g.131374T>G
LRG_287p1:p.Val215Gly
LRG_287p2:p.Val88Gly
NC_000011.9:g.2592594T>G
NM_000218.2:c.644T>G
NM_181798.1:c.263T>G
NR_040711.2:n.537T>G

Protein change:

V125G

Links:

dbSNP: rs368011737

NCBI 1000 Genomes Browser:

rs368011737

Molecular consequence:

NM_000218.3:c.644T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406836.1:c.644T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406837.1:c.374T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_181798.2:c.263T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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uncharacterized protein AT3G07710 [Arabidopsis thaliana]
uncharacterized protein AT3G07710 [Arabidopsis thaliana]
gi|15231499|ref|NP_187428.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005033109	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Feb 7, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 19841300, 25639344, 30571187 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005033109

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Feb 7, 2024)

germline

clinical testing

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

Citation Link

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

Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants.

Kapa S, Tester DJ, Salisbury BA, Harris-Kerr C, Pungliya MS, Alders M, Wilde AA, Ackerman MJ.

Circulation. 2009 Nov 3;120(18):1752-60. doi: 10.1161/CIRCULATIONAHA.109.863076. Epub 2009 Oct 19.

PubMed [citation]

PMID:: 19841300
PMCID:: PMC3025752

Genetic variants in KCNE1, KCNQ1, and NOS1AP in sudden unexplained death during daily activities in Chinese Han population.

Huang J, Wang X, Hao B, Chen Y, Liu H, Quan L, Tang D, Sheng L, Li M, Huang E, Liu C, Luo B.

J Forensic Sci. 2015 Mar;60(2):351-6. doi: 10.1111/1556-4029.12687. Epub 2015 Jan 8. Erratum in: J Forensic Sci. 2018 Jan;63(1):349. doi: 10.1111/1556-4029.13725.

PubMed [citation]

PMID:: 25639344

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV005033109.1

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

Description

The p.V215G variant (also known as c.644T>G), located in coding exon 4 of the KCNQ1 gene, results from a T to G substitution at nucleotide position 644. The valine at codon 215 is replaced by glycine, an amino acid with dissimilar properties. Functional analysis suggests this alteration causes a moderate decrease in channel current; however, the physiological relevance of this result is unclear (Vanoye CG et al. Circ Genom Precis Med, 2018 Nov;11:e002345). This alteration has been reported in an ostensibly healthy control (Kapa S et al. Circulation, 2009 Nov;120:1752-60). This variant has also been reported in a sudden unexplained death cohort (Huang J et al. J Forensic Sci, 2015 Mar;60:351-6). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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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