U.S. flag

An official website of the United States government

NM_000218.3(KCNQ1):c.1781G>C (p.Arg594Pro) AND Cardiovascular phenotype

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Mar 20, 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:
RCV000620919.5

Allele description [Variation Report for NM_000218.3(KCNQ1):c.1781G>C (p.Arg594Pro)]

NM_000218.3(KCNQ1):c.1781G>C (p.Arg594Pro)

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.1781G>C (p.Arg594Pro)
Other names:
p.R594P:CGA>CCA
HGVS:
  • NC_000011.10:g.2778024G>C
  • NG_008935.1:g.338034G>C
  • NM_000218.3:c.1781G>CMANE SELECT
  • NM_001406836.1:c.1685G>C
  • NM_001406837.1:c.1511G>C
  • NM_001406838.1:c.1241G>C
  • NM_001406839.1:c.293G>C
  • NM_181798.2:c.1400G>C
  • NP_000209.2:p.Arg594Pro
  • NP_000209.2:p.Arg594Pro
  • NP_001393765.1:p.Arg562Pro
  • NP_001393766.1:p.Arg504Pro
  • NP_001393767.1:p.Arg414Pro
  • NP_001393768.1:p.Arg98Pro
  • NP_861463.1:p.Arg467Pro
  • NP_861463.1:p.Arg467Pro
  • LRG_287t1:c.1781G>C
  • LRG_287t2:c.1400G>C
  • LRG_287:g.338034G>C
  • LRG_287p1:p.Arg594Pro
  • LRG_287p2:p.Arg467Pro
  • NC_000011.9:g.2799254G>C
  • NM_000218.2:c.1781G>C
  • NM_181798.1:c.1400G>C
  • NR_040711.2:n.1674G>C
  • P51787:p.Arg594Pro
Protein change:
R414P
Links:
UniProtKB: P51787#VAR_075029; dbSNP: rs199472815
NCBI 1000 Genomes Browser:
rs199472815
Molecular consequence:
  • NM_000218.3:c.1781G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406836.1:c.1685G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406837.1:c.1511G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406838.1:c.1241G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406839.1:c.293G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181798.2:c.1400G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000738072Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(Mar 20, 2024) 		germlineclinical testing

PubMed (5)
[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

Whole blood RNA offers a rapid, comprehensive approach to genetic diagnosis of cardiovascular diseases.

Miller TE, You L, Myerburg RJ, Benke PJ, Bishopric NH.

Genet Med. 2007 Jan;9(1):23-33. Erratum in: Genet Med. 2007 Feb;9(2):135.

PubMed [citation]
PMID:
17224687

Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test.

Kapplinger JD, Tester DJ, Salisbury BA, Carr JL, Harris-Kerr C, Pollevick GD, Wilde AA, Ackerman MJ.

Heart Rhythm. 2009 Sep;6(9):1297-303. doi: 10.1016/j.hrthm.2009.05.021. Epub 2009 Jun 23.

PubMed [citation]
PMID:
19716085
PMCID:
PMC3049907
See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV000738072.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

The p.R594P variant (also known as c.1781G>C), located in coding exon 15 of the KCNQ1 gene, results from a G to C substitution at nucleotide position 1781. The arginine at codon 594 is replaced by proline, an amino acid with dissimilar properties, and is located in the C-terminal cytoplasmic assembly domain. This alteration has been associated with long QT syndrome (LQTS) in several individuals, most of whom harbored other KCNQ1 variants, and has been reported in cis with p.T144A (Miller TE et al. Genet. Med. 2007;9:23-33; Kapplinger JD et al. Heart Rhythm. 2009;6:1297-303; Giudicessi JR et al. Circ Cardiovasc Genet. 2013;6:193-200; Bagnall RD et al. N. Engl. J. Med. 2016;374:2441-52). This alteration has also been reported in an ostensibly healthy cohort (Lacaze P et al. NPJ Genom Med, 2021 Jun;6:51). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Another alteration at the same codon, p.R594Q (c.1781G>A), has been described in association with LQTS (Splawski I et al. Circulation. 2000;102(10):1178-85). 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