NM_000218.3(KCNQ1):c.830C>G (p.Ser277Trp) AND Long QT syndrome

Clinical significance:Likely pathogenic (Last evaluated: Oct 2, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000046141.4

Allele description [Variation Report for NM_000218.3(KCNQ1):c.830C>G (p.Ser277Trp)]

NM_000218.3(KCNQ1):c.830C>G (p.Ser277Trp)

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.830C>G (p.Ser277Trp)
Other names:
p.S277W:TCG>TGG
HGVS:
  • NC_000011.10:g.2572895C>G
  • NG_008935.1:g.132905C>G
  • NM_000218.2:c.830C>G
  • NM_000218.3:c.830C>GMANE SELECT
  • NM_181798.1:c.449C>G
  • NP_000209.2:p.Ser277Trp
  • NP_000209.2:p.Ser277Trp
  • NP_861463.1:p.Ser150Trp
  • LRG_287t1:c.830C>G
  • LRG_287t2:c.449C>G
  • LRG_287:g.132905C>G
  • LRG_287p1:p.Ser277Trp
  • LRG_287p2:p.Ser150Trp
  • NC_000011.9:g.2594125C>G
  • NC_000011.9:g.2594125C>G
  • P51787:p.Ser277Trp
Protein change:
S150W
Links:
UniProtKB: P51787#VAR_074970; dbSNP: rs199472730
NCBI 1000 Genomes Browser:
rs199472730
Molecular consequence:
  • NM_000218.2:c.830C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000218.3:c.830C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181798.1:c.449C>G - 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
SCV000074154Invitaecriteria provided, single submitter
Likely pathogenic
(Oct 2, 2019)
germlineclinical testing

PubMed (6)
[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

Genetic testing in the long QT syndrome: development and validation of an efficient approach to genotyping in clinical practice.

Napolitano C, Priori SG, Schwartz PJ, Bloise R, Ronchetti E, Nastoli J, Bottelli G, Cerrone M, Leonardi S.

JAMA. 2005 Dec 21;294(23):2975-80.

PubMed [citation]
PMID:
16414944

Genotype- and Sex-Specific QT-RR Relationship in the Type-1 Long-QT Syndrome.

Couderc JP, Xia X, Denjoy I, Extramiana F, Maison-Blanche P, Moss AJ, Zareba W, Lopes CM.

J Am Heart Assoc. 2012 Apr;1(2):e000570. doi: 10.1161/JAHA.112.000570. Epub 2012 Apr 24.

PubMed [citation]
PMID:
23130128
PMCID:
PMC3487370
See all PubMed Citations (6)

Details of each submission

From Invitae, SCV000074154.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

This sequence change replaces serine with tryptophan at codon 277 of the KCNQ1 protein (p.Ser277Trp). The serine residue is highly conserved and there is a large physicochemical difference between serine and tryptophan. This variant is not present in population databases (rs199472730, ExAC no frequency). This variant has been reported in several individuals affected with long QT syndrome (PMID: 16414944, 23130128). ClinVar contains an entry for this variant (Variation ID: 53115). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. A different missense substitution at this codon (p.Ser277Leu) has been determined to be pathogenic (PMID: 12442276, 21241880, 21895724). This suggests that the serine residue is critical for KCNQ1 protein function and that other missense substitutions at this position may also be pathogenic. 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 25, 2021

Support Center