NM_181798.1(KCNQ1):c.179T>C (p.Leu60Pro) AND Long QT syndrome

Clinical significance:Likely pathogenic (Last evaluated: Sep 10, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000046081.6

Allele description [Variation Report for NM_181798.1(KCNQ1):c.179T>C (p.Leu60Pro)]

NM_181798.1(KCNQ1):c.179T>C (p.Leu60Pro)

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_181798.1(KCNQ1):c.179T>C (p.Leu60Pro)
Other names:
p.L187P:CTC>CCC
HGVS:
  • NC_000011.10:g.2570710T>C
  • NG_008935.1:g.130720T>C
  • NM_000218.2:c.560T>C
  • NM_181798.1:c.179T>C
  • NP_000209.2:p.Leu187Pro
  • NP_861463.1:p.Leu60Pro
  • LRG_287t1:c.560T>C
  • LRG_287t2:c.179T>C
  • LRG_287:g.130720T>C
  • LRG_287p1:p.Leu187Pro
  • LRG_287p2:p.Leu60Pro
  • NC_000011.9:g.2591940T>C
Protein change:
L187P
Links:
dbSNP: rs199473399
NCBI 1000 Genomes Browser:
rs199473399
Molecular consequence:
  • NM_000218.2:c.560T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181798.1:c.179T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Long QT syndrome (LQTS)
Identifiers:
MONDO: MONDO:0002442; MeSH: D008133; MedGen: C0023976; OMIM: PS192500

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000074094Invitaecriteria provided, single submitter
Likely pathogenic
(Sep 10, 2020)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Protective effect of KCNH2 single nucleotide polymorphism K897T in LQTS families and identification of novel KCNQ1 and KCNH2 mutations.

Zhang X, Chen S, Zhang L, Liu M, Redfearn S, Bryant RM, Oberti C, Vincent GM, Wang QK.

BMC Med Genet. 2008 Sep 23;9:87. doi: 10.1186/1471-2350-9-87.

PubMed [citation]
PMID:
18808722
PMCID:
PMC2570672

Results of genetic testing in 855 consecutive unrelated patients referred for long QT syndrome in a clinical laboratory.

Lieve KV, Williams L, Daly A, Richard G, Bale S, Macaya D, Chung WK.

Genet Test Mol Biomarkers. 2013 Jul;17(7):553-61. doi: 10.1089/gtmb.2012.0118. Epub 2013 Apr 30.

PubMed [citation]
PMID:
23631430
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV000074094.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change replaces leucine with proline at codon 187 of the KCNQ1 protein (p.Leu187Pro). The leucine residue is weakly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is present in population databases (rs199473399, ExAC 0.002%). This variant has been reported to segregate with LQT (LQT) syndrome in a large multigenerational family (PMID: 18808722). It has also been reported in several individuals affected with LQT syndrome (PMID: 18808722, 23631430). However, in one individual, one pathogenic allele c.1663C>T (p.Arg555Cys) was also identified in the KCNQ1 gene. The phase of these two variants is unknown. ClinVar contains an entry for this variant (Variation ID: 53066). This variant has been reported to have conflicting or insufficient data to determine the effect on KCNQ1 protein function (PMID: 30571187). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Oct 7, 2021

Support Center