NM_181798.1(KCNQ1):c.632C>T (p.Ser211Phe) AND Long QT syndrome

Clinical significance:Likely pathogenic (Last evaluated: Sep 26, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000045928.3

Allele description [Variation Report for NM_181798.1(KCNQ1):c.632C>T (p.Ser211Phe)]

NM_181798.1(KCNQ1):c.632C>T (p.Ser211Phe)

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.632C>T (p.Ser211Phe)
HGVS:
  • NC_000011.10:g.2583526C>T
  • NG_008935.1:g.143536C>T
  • NM_000218.2:c.1013C>T
  • NM_181798.1:c.632C>T
  • NP_000209.2:p.Ser338Phe
  • NP_861463.1:p.Ser211Phe
  • LRG_287t1:c.1013C>T
  • LRG_287t2:c.632C>T
  • LRG_287:g.143536C>T
  • LRG_287p1:p.Ser338Phe
  • LRG_287p2:p.Ser211Phe
  • NC_000011.9:g.2604756C>T
Protein change:
S211F
Links:
dbSNP: rs199472758
NCBI 1000 Genomes Browser:
rs199472758
Molecular consequence:
  • NM_000218.2:c.1013C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181798.1:c.632C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000073941Invitaecriteria provided, single submitter
Likely pathogenic
(Sep 26, 2016)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000073941.4

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

Description

This sequence change replaces serine with phenylalanine at codon 338 of the KCNQ1 protein (p.Ser338Phe). The serine residue is highly conserved and there is a large physicochemical difference between serine and phenylalanine. This variant is not present in population databases (ExAC no frequency) . This variant was reported in an individual and also a family affected with long QT syndrome (PMID: 19862833, 23291057). ClinVar contains an entry for this variant (Variation ID: 52928). This variant identified in the KCNQ1 gene is located in the transmembrane S6 region of the resulting protein (PMID: 19841300, 25348405). For more information about the location of this variant, please visit www.invitae.com/KCNQ1-topology. In an experimental study using a model organism, this variant was not shown to affect trafficking to the membrane but it was shown to affect conductance across the channel (PMID:23291057). In summary, this variant is a rare missense change that has been reported in several individuals affected with lQT and has some some evidence of causing a deleterious effect on protein function. Therefore, it has been classified as Likely Pathogenic.

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

Last Updated: Oct 7, 2021

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