NM_181798.1(KCNQ1):c.1175G>A (p.Arg392His) AND Long QT syndrome

Clinical significance:Uncertain significance (Last evaluated: Jun 4, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000543065.5

Allele description [Variation Report for NM_181798.1(KCNQ1):c.1175G>A (p.Arg392His)]

NM_181798.1(KCNQ1):c.1175G>A (p.Arg392His)

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.1175G>A (p.Arg392His)
HGVS:
  • NC_000011.10:g.2768885G>A
  • NG_008935.1:g.328895G>A
  • NM_000218.2:c.1556G>A
  • NM_181798.1:c.1175G>A
  • NP_000209.2:p.Arg519His
  • NP_861463.1:p.Arg392His
  • LRG_287t1:c.1556G>A
  • LRG_287t2:c.1175G>A
  • LRG_287:g.328895G>A
  • LRG_287p1:p.Arg519His
  • LRG_287p2:p.Arg392His
  • NC_000011.9:g.2790115G>A
Protein change:
R392H
Links:
dbSNP: rs199472788
NCBI 1000 Genomes Browser:
rs199472788
Molecular consequence:
  • NM_000218.2:c.1556G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181798.1:c.1175G>A - 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
SCV000627378Invitaecriteria provided, single submitter
Uncertain significance
(Jun 4, 2020)
germlineclinical testing

PubMed (5)
[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

A Common Mutation of Long QT Syndrome Type 1 in Japan.

Itoh H, Dochi K, Shimizu W, Denjoy I, Ohno S, Aiba T, Kimura H, Kato K, Fukuyama M, Hasagawa K, Schulze-Bahr E, Guicheney P, Horie M.

Circ J. 2015;79(9):2026-30. doi: 10.1253/circj.CJ-15-0342. Epub 2015 Jun 29.

PubMed [citation]
PMID:
26118460

Ethnic differences in cardiac potassium channel variants: implications for genetic susceptibility to sudden cardiac death and genetic testing for congenital long QT syndrome.

Ackerman MJ, Tester DJ, Jones GS, Will ML, Burrow CR, Curran ME.

Mayo Clin Proc. 2003 Dec;78(12):1479-87.

PubMed [citation]
PMID:
14661677
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV000627378.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change replaces arginine with histidine at codon 519 of the KCNQ1 protein (p.Arg519His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs199472788, ExAC 0.01%). This variant has been reported in three individuals affected with long QT syndrome (PMID: 26118460), as well as in two healthy individuals (PMID: 19841300, 14661677). ClinVar contains an entry for this variant (Variation ID: 67038). This variant identified in the KCNQ1 gene is located in the cytoplasmic C-terminal region of the resulting protein (PMID: 19841300, 25348405). For more information about the location of this variant, please visit www.invitae.com/KCNQ1-topology. It is unclear how this variant impacts the function of this protein. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). In summary, this variant has uncertain impact on KCNQ1 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Oct 7, 2021

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