U.S. flag

An official website of the United States government

NM_000218.3(KCNQ1):c.1189C>T (p.Arg397Trp) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jun 19, 2020
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:
RCV002467560.9

Allele description [Variation Report for NM_000218.3(KCNQ1):c.1189C>T (p.Arg397Trp)]

NM_000218.3(KCNQ1):c.1189C>T (p.Arg397Trp)

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.1189C>T (p.Arg397Trp)
Other names:
p.R397W:CGG>TGG
HGVS:
  • NC_000011.10:g.2587630C>T
  • NG_008935.1:g.147640C>T
  • NM_000218.3:c.1189C>TMANE SELECT
  • NM_001406836.1:c.1093C>T
  • NM_001406837.1:c.919C>T
  • NM_001406838.1:c.649C>T
  • NM_181798.2:c.808C>T
  • NP_000209.2:p.Arg397Trp
  • NP_000209.2:p.Arg397Trp
  • NP_001393765.1:p.Arg365Trp
  • NP_001393766.1:p.Arg307Trp
  • NP_001393767.1:p.Arg217Trp
  • NP_861463.1:p.Arg270Trp
  • NP_861463.1:p.Arg270Trp
  • LRG_287t1:c.1189C>T
  • LRG_287t2:c.808C>T
  • LRG_287:g.147640C>T
  • LRG_287p1:p.Arg397Trp
  • LRG_287p2:p.Arg270Trp
  • NC_000011.9:g.2608860C>T
  • NM_000218.2:c.1189C>T
  • NM_181798.1:c.808C>T
  • NR_040711.2:n.1082C>T
  • P51787:p.Arg397Trp
Protein change:
R217W
Links:
UniProtKB: P51787#VAR_075001; dbSNP: rs199472776
Molecular consequence:
  • NM_000218.3:c.1189C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406836.1:c.1093C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406837.1:c.919C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406838.1:c.649C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181798.2:c.808C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Atrial fibrillation, familial, 3 (ATFB3)
Identifiers:
MONDO: MONDO:0011857; MedGen: C1837014; OMIM: 607554
Name:
Long QT syndrome 1 (LQT1)
Identifiers:
MONDO: MONDO:0100316; MedGen: C4551647; Orphanet: 101016; Orphanet: 768; OMIM: 192500
Name:
Jervell and Lange-Nielsen syndrome 1 (JLNS1)
Synonyms:
CARDIOAUDITORY SYNDROME OF JERVELL AND LANGE-NIELSEN; DEAFNESS, CONGENITAL, AND FUNCTIONAL HEART DISEASE; PROLONGED QT INTERVAL IN EKG AND SUDDEN DEATH; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0024540; MedGen: C4551509; Orphanet: 768; Orphanet: 90647; OMIM: 220400
Name:
Short QT syndrome type 2
Identifiers:
MONDO: MONDO:0012313; MedGen: C1865019; Orphanet: 51083; OMIM: 609621

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
SCV002764487New York Genome Center
criteria provided, single submitter

(NYGC Assertion Criteria 2020)		Uncertain significance
(Jun 19, 2020) 		germlineclinical testing

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Details of each submission

From New York Genome Center, SCV002764487.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided

Description

The c.1189C>T (p.Arg397Trp) variant identified in the KCNQ1 gene substitutes a well conserved Arginine for Tryptophan at amino acid 397/677 (exon 9/16), and is also referred to asp.Arg270Trp annotated from transcript NM_181798.1. This variant is reported in gnomAD with an allele frequency of 1.26e-4 (v3.0; 18 heterozygotes, 0 homozygotes)and 1.88e-4 (v2.1.1; 53 heterozygotes, 0 homozygotes). In silico algorithms predict this variant to be Deleterious (SIFT; score: 0.001), Damaging (Provean; score: -3.32),and Pathogenic (REVEL; score: 0.7599) to the function of the canonical transcript. The p.Arg397 residue is in the intracellular C-terminal domain of KCNQ1 (UniProtKB:P51787). This variant has been reported many times in ClinVar with varying interpretations including Likely Pathogenic, Benign, and a Variant of Uncertain Significance (VarID:52970). The c.1189C>T (p.Arg397Trp) variant identified here has been reported in several affected individuals in the literature [PMID:17470695;PMID:19841300;PMID:22199116;PMID:22456477;PMID:24440382], however many of these studies were panel based and examined only a small number of potentially causative genes. Functional studies suggest the p.Arg397Trp variant leads to reduced current densities [PMID:23571586;PMID:24190995], and may be involved in coordination of ATP binding [PMID:24190995]. While it has been observed in several affected individuals and in vitro functional studies suggest an effect on current density, the presence of this variant at an allele frequency higher than expected in control databases leave some uncertainty regarding its pathogenicity. Given that, the c.1189C>T (p.Arg397Trp) variant identified in the KCNQ1 gene is reported as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

Last Updated: Jul 27, 2026

Modify your search Search (all fields optional) Clear all
Advanced Search