NM_000238.4(KCNH2):c.1871G>A (p.Ser624Asn) AND Cardiovascular phenotype

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 11, 2021
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:: RCV002406969.1

Allele description

NM_000238.4(KCNH2):c.1871G>A (p.Ser624Asn)

Gene:

KCNH2:potassium voltage-gated channel subfamily H member 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q36.1

Genomic location:

Preferred name:

NM_000238.4(KCNH2):c.1871G>A (p.Ser624Asn)

HGVS:

NC_000007.14:g.150951522C>T
NG_008916.1:g.31405G>A
NM_000238.4:c.1871G>AMANE SELECT
NM_001204798.2:c.851G>A
NM_001406753.1:c.1583G>A
NM_001406755.1:c.1694G>A
NM_001406756.1:c.1583G>A
NM_001406757.1:c.1571G>A
NM_172056.3:c.1871G>A
NM_172057.3:c.851G>A
NP_000229.1:p.Ser624Asn
NP_000229.1:p.Ser624Asn
NP_001191727.1:p.Ser284Asn
NP_001393682.1:p.Ser528Asn
NP_001393684.1:p.Ser565Asn
NP_001393685.1:p.Ser528Asn
NP_001393686.1:p.Ser524Asn
NP_742053.1:p.Ser624Asn
NP_742053.1:p.Ser624Asn
NP_742054.1:p.Ser284Asn
NP_742054.1:p.Ser284Asn
LRG_288t1:c.1871G>A
LRG_288t2:c.1871G>A
LRG_288t3:c.851G>A
LRG_288:g.31405G>A
LRG_288p1:p.Ser624Asn
LRG_288p2:p.Ser624Asn
LRG_288p3:p.Ser284Asn
NC_000007.13:g.150648610C>T
NM_000238.3:c.1871G>A
NM_172056.2:c.1871G>A
NM_172057.2:c.851G>A
NR_176254.1:n.2279G>A
NR_176255.1:n.1152G>A

Protein change:

S284N

Links:

dbSNP: rs777410293

NCBI 1000 Genomes Browser:

rs777410293

Molecular consequence:

NM_000238.4:c.1871G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001204798.2:c.851G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406753.1:c.1583G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406755.1:c.1694G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406756.1:c.1583G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406757.1:c.1571G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_172056.3:c.1871G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_172057.3:c.851G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002722326	Ambry Genetics	criteria provided, single submitter (Ambry General Variant Classification Scheme_2022)	Uncertain significance (Oct 11, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 18690032, 28431243 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002722326

Ambry Genetics

criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)

Uncertain significance
(Oct 11, 2021)

germline

clinical testing

PubMed (2)
[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	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

Mutational analysis of block and facilitation of HERG current by a class III anti-arrhythmic agent, nifekalant.

Hosaka Y, Iwata M, Kamiya N, Yamada M, Kinoshita K, Fukunishi Y, Tsujimae K, Hibino H, Aizawa Y, Inanobe A, Nakamura H, Kurachi Y.

Channels (Austin). 2007 May-Jun;1(3):198-208. Epub 2007 Jul 6.

PubMed [citation]

PMID:: 18690032

Cryo-EM Structure of the Open Human Ether-à-go-go-Related K(+) Channel hERG.

Wang W, MacKinnon R.

Cell. 2017 Apr 20;169(3):422-430.e10. doi: 10.1016/j.cell.2017.03.048.

PubMed [citation]

PMID:: 28431243
PMCID:: PMC5484391

Details of each submission

From Ambry Genetics, SCV002722326.1

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

Description

The p.S624N variant (also known as c.1871G>A), located in coding exon 7 of the KCNH2 gene, results from a G to A substitution at nucleotide position 1871. The serine at codon 624 is replaced by asparagine, an amino acid with highly similar properties. This alteration impacts the highly conserved ion selectivity filter (SVGFGN) located between transmembrane helices S5 and S6. Based on internal structural analysis, p.S624N decreases the structural stability of this motif (Ambry internal data; Wang W et al. Cell, 2017 04;169:422-430.e10). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. 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	1	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Dec 24, 2023

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