NM_181798.1(KCNQ1):c.449C>G (p.Ser150Trp) AND not provided

Clinical significance:Pathogenic (Last evaluated: Jan 16, 2012)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000182308.1

Allele description [Variation Report for NM_181798.1(KCNQ1):c.449C>G (p.Ser150Trp)]

NM_181798.1(KCNQ1):c.449C>G (p.Ser150Trp)

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.449C>G (p.Ser150Trp)
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_181798.1:c.449C>G
  • 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
  • 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_181798.1:c.449C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000234611GeneDxcriteria provided, single submitter
Pathogenic
(Jan 16, 2012)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From GeneDx, SCV000234611.10

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

This missense change is denoted Ser277Trp (aka S277W) at the protein level and c.830 C>G at the cDNA level. The Ser277Trp mutation in the KCNQ1 gene has been reported previously in association with LQTS, and this mutation was absent from 800 control alleles (Napolitano C et al., 2005). The NHLBI ESP Exome Variant Server reports Ser277Trp was not observed in approximately 5,000 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. In addition, functional studies of a similar missense mutation (Ser277Leu) reported this mutation suppresses normal KCNQ1 channel function (Aidery P et al., 2011). Ser277Trp results in a non-conservative amino acid substitution of a neutral, polar Serine with a non-polar Tryptophan at a residue that is conserved across species. Furthermore, different missense mutations at the same codon (Ser277Leu, Ser277Pro), as well as mutations in nearby codons (Phe275Ser,Trp278His) have also been reported in association with LQTS, further supporting the functional importance of this region of the protein. The variant is found in LQT panel(s).

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

Last Updated: Oct 8, 2021

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