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NM_000218.3(KCNQ1):c.458C>T (p.Thr153Met) AND Cardiac arrhythmia

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Mar 24, 2023
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:
RCV001841681.11

Allele description [Variation Report for NM_000218.3(KCNQ1):c.458C>T (p.Thr153Met)]

NM_000218.3(KCNQ1):c.458C>T (p.Thr153Met)

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.458C>T (p.Thr153Met)
HGVS:
  • NC_000011.10:g.2527999C>T
  • NG_008935.1:g.88009C>T
  • NM_000218.3:c.458C>TMANE SELECT
  • NM_001406836.1:c.458C>T
  • NM_001406837.1:c.188C>T
  • NM_001406838.1:c.458C>T
  • NM_181798.2:c.77C>T
  • NP_000209.2:p.Thr153Met
  • NP_000209.2:p.Thr153Met
  • NP_001393765.1:p.Thr153Met
  • NP_001393766.1:p.Thr63Met
  • NP_001393767.1:p.Thr153Met
  • NP_861463.1:p.Thr26Met
  • NP_861463.1:p.Thr26Met
  • LRG_287t1:c.458C>T
  • LRG_287t2:c.77C>T
  • LRG_287:g.88009C>T
  • LRG_287p1:p.Thr153Met
  • LRG_287p2:p.Thr26Met
  • NC_000011.9:g.2549229C>T
  • NM_000218.2:c.458C>T
  • NM_181798.1:c.77C>T
  • NR_040711.2:n.351C>T
  • P51787:p.Thr153Met
Protein change:
T153M
Links:
UniProtKB: P51787#VAR_074938; dbSNP: rs143709408
NCBI 1000 Genomes Browser:
rs143709408
Molecular consequence:
  • NM_000218.3:c.458C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406836.1:c.458C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406837.1:c.188C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406838.1:c.458C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181798.2:c.77C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cardiac arrhythmia
Synonyms:
Cardiac rhythm disease
Identifiers:
EFO: EFO_0004269; MONDO: MONDO:0007263; MedGen: C0003811; Human Phenotype Ontology: HP:0011675

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000904959Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Mar 24, 2023) 		germlineclinical testing

PubMed (7)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

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

Genetic complexity in hypertrophic cardiomyopathy revealed by high-throughput sequencing.

Lopes LR, Zekavati A, Syrris P, Hubank M, Giambartolomei C, Dalageorgou C, Jenkins S, McKenna W; Uk10k Consortium, Plagnol V, Elliott PM.

J Med Genet. 2013 Apr;50(4):228-39. doi: 10.1136/jmedgenet-2012-101270. Epub 2013 Feb 8.

PubMed [citation]
PMID:
23396983
PMCID:
PMC3607113
See all PubMed Citations (7)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV000904959.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

This missense variant replaces threonine with methionine at codon 153 of the KCNQ1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). A functional study has shown the variant to result in a partially reduced sodium current density compared to the wild type (PMID: 30571187). This variant has been reported in a few individuals affected with long QT syndrome (PMID: 19716085, 28794082, 29197658). One of these individuals carried a disease-causing variant in a different gene that could explain the observed phenotype (PMID: 28794082). This variant has also been observed in an individual affected with hypertrophic cardiomyopathy (PMID: 23396983) and in another individual who experienced sudden unexplained death (PMID: 36293497). This variant has been identified in 49/282700 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The relatively high frequency of this variant in the general population suggests that this variant is unlikely to be disease-causing. However, additional studies are necessary to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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

Last Updated: Nov 24, 2024