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NM_000238.4(KCNH2):c.1894C>G (p.Pro632Ala) AND Cardiovascular phenotype

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Dec 27, 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:
RCV002413860.2

Allele description [Variation Report for NM_000238.4(KCNH2):c.1894C>G (p.Pro632Ala)]

NM_000238.4(KCNH2):c.1894C>G (p.Pro632Ala)

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.1894C>G (p.Pro632Ala)
HGVS:
  • NC_000007.14:g.150951499G>C
  • NG_008916.1:g.31428C>G
  • NM_000238.4:c.1894C>GMANE SELECT
  • NM_001204798.2:c.874C>G
  • NM_001406753.1:c.1606C>G
  • NM_001406755.1:c.1717C>G
  • NM_001406756.1:c.1606C>G
  • NM_001406757.1:c.1594C>G
  • NM_172056.3:c.1894C>G
  • NM_172057.3:c.874C>G
  • NP_000229.1:p.Pro632Ala
  • NP_000229.1:p.Pro632Ala
  • NP_001191727.1:p.Pro292Ala
  • NP_001393682.1:p.Pro536Ala
  • NP_001393684.1:p.Pro573Ala
  • NP_001393685.1:p.Pro536Ala
  • NP_001393686.1:p.Pro532Ala
  • NP_742053.1:p.Pro632Ala
  • NP_742053.1:p.Pro632Ala
  • NP_742054.1:p.Pro292Ala
  • NP_742054.1:p.Pro292Ala
  • LRG_288t1:c.1894C>G
  • LRG_288t2:c.1894C>G
  • LRG_288t3:c.874C>G
  • LRG_288:g.31428C>G
  • LRG_288p1:p.Pro632Ala
  • LRG_288p2:p.Pro632Ala
  • LRG_288p3:p.Pro292Ala
  • NC_000007.13:g.150648587G>C
  • NM_000238.3:c.1894C>G
  • NM_172056.2:c.1894C>G
  • NM_172057.2:c.874C>G
  • NR_176254.1:n.2302C>G
  • NR_176255.1:n.1175C>G
Protein change:
P292A
Links:
dbSNP: rs199473527
NCBI 1000 Genomes Browser:
rs199473527
Molecular consequence:
  • NM_000238.4:c.1894C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001204798.2:c.874C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406753.1:c.1606C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406755.1:c.1717C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406756.1:c.1606C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406757.1:c.1594C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172056.3:c.1894C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172057.3:c.874C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002723898Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(Dec 27, 2019) 		germlineclinical testing

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

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2.

Splawski I, Shen J, Timothy KW, Lehmann MH, Priori S, Robinson JL, Moss AJ, Schwartz PJ, Towbin JA, Vincent GM, Keating MT.

Circulation. 2000 Sep 5;102(10):1178-85.

PubMed [citation]
PMID:
10973849

Risk for life-threatening cardiac events in patients with genotype-confirmed long-QT syndrome and normal-range corrected QT intervals.

Goldenberg I, Horr S, Moss AJ, Lopes CM, Barsheshet A, McNitt S, Zareba W, Andrews ML, Robinson JL, Locati EH, Ackerman MJ, Benhorin J, Kaufman ES, Napolitano C, Platonov PG, Priori SG, Qi M, Schwartz PJ, Shimizu W, Towbin JA, Vincent GM, Wilde AA, et al.

J Am Coll Cardiol. 2011 Jan 4;57(1):51-9. doi: 10.1016/j.jacc.2010.07.038.

PubMed [citation]
PMID:
21185501
PMCID:
PMC3332533
See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV002723898.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

The p.P632A variant (also known as c.1894C>G), located in coding exon 7 of the KCNH2 gene, results from a C to G substitution at nucleotide position 1894. The proline at codon 632 is replaced by alanine, an amino acid with highly similar properties, and is located in the pore region. This alteration has been detected in long QT syndrome (LQTS) cohorts, though clinical details were not provided (Goldenberg I et al. J Am Coll Cardiol. 2011;57(1):51-9; Mullally J et al. Heart Rhythm. 2013;10:378-82). Another alteration affecting this amino acid (p.P632S, c.1894C>T) has been previously reported in association with LQTS (Splawski I et al. Circulation. 2000;102(10):1178-85). In addition, internal structural analysis predicts this alteration to be structurally deleterious (Liu J et al. J Gen Physiol. 2002;120(5):723-37; Long SB et al. Nature. 2007;450(7168):376-82). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024