NM_000891.2(KCNJ2):c.653G>T (p.Arg218Leu) AND multiple conditions

Clinical significance:Uncertain significance (Last evaluated: Jul 16, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000470921.1

Allele description [Variation Report for NM_000891.2(KCNJ2):c.653G>T (p.Arg218Leu)]

NM_000891.2(KCNJ2):c.653G>T (p.Arg218Leu)

Gene:
KCNJ2:potassium voltage-gated channel subfamily J member 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q24.3
Genomic location:
Preferred name:
NM_000891.2(KCNJ2):c.653G>T (p.Arg218Leu)
Other names:
p.R218L:CGG>CTG
HGVS:
  • NC_000017.11:g.70175692G>T
  • NG_008798.1:g.11158G>T
  • NM_000891.2:c.653G>T
  • NP_000882.1:p.Arg218Leu
  • LRG_328t1:c.653G>T
  • LRG_328:g.11158G>T
  • LRG_328p1:p.Arg218Leu
  • NC_000017.10:g.68171833G>T
Protein change:
R218L
Links:
dbSNP: rs199473384
NCBI 1000 Genomes Browser:
rs199473384
Molecular consequence:
  • NM_000891.2:c.653G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Andersen Tawil syndrome (LQT7)
Synonyms:
Andersen Syndrome
Identifiers:
MedGen: C1563715; Orphanet: 37553; OMIM: 170390
Name:
Short QT syndrome 3 (SQT3)
Identifiers:
MedGen: C1865018; Orphanet: 51083; OMIM: 609622

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000541388Invitaecriteria provided, single submitter
Uncertain significance
(Jul 16, 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.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000541388.2

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

Description

This sequence change replaces arginine with leucine at codon 218 of the KCNJ2 protein (p.Arg218Leu). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and leucine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a KCNJ2-related disease. 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.Arg218Trp) has been determined to be pathogenic (PMID: 11371347, 12909315, 25415519, 14522976, 20647529). This suggests that the arginine residue is critical for KCNJ2 protein function and that other missense substitutions at this position may also be pathogenic. In summary, this variant is a novel missense change with uncertain impact on protein function. 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: Apr 17, 2019

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