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NM_000218.3(KCNQ1):c.1555C>T (p.Arg519Cys) AND Cardiac arrhythmia

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Oct 22, 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:
RCV001841669.11

Allele description [Variation Report for NM_000218.3(KCNQ1):c.1555C>T (p.Arg519Cys)]

NM_000218.3(KCNQ1):c.1555C>T (p.Arg519Cys)

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.1555C>T (p.Arg519Cys)
HGVS:
  • NC_000011.10:g.2768884C>T
  • NG_008935.1:g.328894C>T
  • NM_000218.3:c.1555C>TMANE SELECT
  • NM_001406836.1:c.1459C>T
  • NM_001406837.1:c.1285C>T
  • NM_001406838.1:c.1015C>T
  • NM_181798.2:c.1174C>T
  • NP_000209.2:p.Arg519Cys
  • NP_000209.2:p.Arg519Cys
  • NP_001393765.1:p.Arg487Cys
  • NP_001393766.1:p.Arg429Cys
  • NP_001393767.1:p.Arg339Cys
  • NP_861463.1:p.Arg392Cys
  • NP_861463.1:p.Arg392Cys
  • LRG_287t1:c.1555C>T
  • LRG_287t2:c.1174C>T
  • LRG_287:g.328894C>T
  • LRG_287p1:p.Arg519Cys
  • LRG_287p2:p.Arg392Cys
  • NC_000011.9:g.2790114C>T
  • NM_000218.2:c.1555C>T
  • NM_181798.1:c.1174C>T
  • NR_040711.2:n.1448C>T
Protein change:
R339C
Links:
dbSNP: rs199472787
NCBI 1000 Genomes Browser:
rs199472787
Molecular consequence:
  • NM_000218.3:c.1555C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406836.1:c.1459C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406837.1:c.1285C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406838.1:c.1015C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181798.2:c.1174C>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
SCV000913650Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Oct 22, 2023) 		germlineclinical testing

PubMed (3)
[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

The use of genotype-phenotype correlations in mutation analysis for the long QT syndrome.

Van Langen IM, Birnie E, Alders M, Jongbloed RJ, Le Marec H, Wilde AA.

J Med Genet. 2003 Feb;40(2):141-5. No abstract available.

PubMed [citation]
PMID:
12566525
PMCID:
PMC1735373

Enhancing rare variant interpretation in inherited arrhythmias through quantitative analysis of consortium disease cohorts and population controls.

Walsh R, Lahrouchi N, Tadros R, Kyndt F, Glinge C, Postema PG, Amin AS, Nannenberg EA, Ware JS, Whiffin N, Mazzarotto F, Škorić-Milosavljević D, Krijger C, Arbelo E, Babuty D, Barajas-Martinez H, Beckmann BM, Bézieau S, Bos JM, Breckpot J, Campuzano O, Castelletti S, et al.

Genet Med. 2021 Jan;23(1):47-58. doi: 10.1038/s41436-020-00946-5. Epub 2020 Sep 7.

PubMed [citation]
PMID:
32893267
PMCID:
PMC7790744
See all PubMed Citations (3)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV000913650.4

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

Description

This missense variant replaces arginine with cysteine at codon 519 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). This variant is found within a highly conserved C-terminus region (a.a. 509-575). Rare non-truncating variants in this region have been shown to be significantly overrepresented in individuals with long QT syndrome (PMID: 32893267). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in two individuals affected with long QT syndrome (PMID: 12566525, Kostereva 2022 DOI: 10.35336/VA-2022-1-02). This variant has been identified in 11/251406 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient 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: Oct 13, 2024