NM_181798.1(KCNQ1):c.263T>G (p.Val88Gly) AND Long QT syndrome

Clinical significance:Uncertain significance (Last evaluated: Mar 13, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000559784.1

Allele description [Variation Report for NM_181798.1(KCNQ1):c.263T>G (p.Val88Gly)]

NM_181798.1(KCNQ1):c.263T>G (p.Val88Gly)

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.263T>G (p.Val88Gly)
HGVS:
  • NC_000011.10:g.2571364T>G
  • NG_008935.1:g.131374T>G
  • NM_000218.2:c.644T>G
  • NM_181798.1:c.263T>G
  • NP_000209.2:p.Val215Gly
  • NP_861463.1:p.Val88Gly
  • LRG_287t1:c.644T>G
  • LRG_287t2:c.263T>G
  • LRG_287:g.131374T>G
  • LRG_287p1:p.Val215Gly
  • LRG_287p2:p.Val88Gly
  • NC_000011.9:g.2592594T>G
Protein change:
V215G
Links:
dbSNP: rs368011737
NCBI 1000 Genomes Browser:
rs368011737
Molecular consequence:
  • NM_000218.2:c.644T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181798.1:c.263T>G - 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
SCV000627396Invitaecriteria provided, single submitter
Uncertain significance
(Mar 13, 2017)
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, SCV000627396.1

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

Description

This sequence change replaces valine with glycine at codon 215 of the KCNQ1 protein (p.Val215Gly). The valine residue is highly conserved and there is a moderate physicochemical difference between valine and glycine. This variant is present in population databases (rs368011737, ExAC 0.002%) but has not been reported in the literature in individuals with a KCNQ1-related disease. This variant identified in the KCNQ1 gene is located in the transmembrane S3 region of the resulting protein (PMID: 19841300, 25348405). For more information about the location of this variant, please visit www.invitae.com/KCNQ1-topology. 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.Val215Met) has been determined to be pathogenic (PMID: 16414944, 19841300, 20421371, 23098067, 23392653). This suggests that the valine residue is critical for KCNQ1 protein function and that other missense substitutions at this position may also be pathogenic. In summary, this variant is a rare missense change that affects a residue that is important for protein function. However, in the absence of confirmed segregation or functional studies, at this time this change 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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