NM_000218.3(KCNQ1):c.1861G>A (p.Gly621Ser) AND Long QT syndrome

Clinical significance:Uncertain significance (Last evaluated: Dec 29, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000471820.2

Allele description [Variation Report for NM_000218.3(KCNQ1):c.1861G>A (p.Gly621Ser)]

NM_000218.3(KCNQ1):c.1861G>A (p.Gly621Ser)

Genes:
KCNQ1-AS1:KCNQ1 antisense RNA 1 [Gene - HGNC]
KCNQ1:potassium voltage-gated channel subfamily Q member 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11p15.4
Genomic location:
Preferred name:
NM_000218.3(KCNQ1):c.1861G>A (p.Gly621Ser)
HGVS:
  • NC_000011.10:g.2847833G>A
  • NG_008935.1:g.407843G>A
  • NM_000218.2:c.1861G>A
  • NM_000218.3:c.1861G>AMANE SELECT
  • NM_181798.1:c.1480G>A
  • NP_000209.2:p.Gly621Ser
  • NP_000209.2:p.Gly621Ser
  • NP_861463.1:p.Gly494Ser
  • LRG_287t1:c.1861G>A
  • LRG_287t2:c.1480G>A
  • LRG_287:g.407843G>A
  • LRG_287p1:p.Gly621Ser
  • LRG_287p2:p.Gly494Ser
  • NC_000011.9:g.2869063G>A
Protein change:
G494S
Links:
dbSNP: rs199472820
NCBI 1000 Genomes Browser:
rs199472820
Molecular consequence:
  • NM_000218.2:c.1861G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000218.3:c.1861G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181798.1:c.1480G>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
SCV000543320Invitaecriteria provided, single submitter
Uncertain significance
(Dec 29, 2019)
germlineclinical testing

PubMed (3)
[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

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

Post-mortem genetic analysis in juvenile cases of sudden cardiac death.

Campuzano O, Sanchez-Molero O, Allegue C, Coll M, Mademont-Soler I, Selga E, Ferrer-Costa C, Mates J, Iglesias A, Sarquella-Brugada G, Cesar S, Brugada J, Castellà J, Medallo J, Brugada R.

Forensic Sci Int. 2014 Dec;245:30-7. doi: 10.1016/j.forsciint.2014.10.004. Epub 2014 Oct 14.

PubMed [citation]
PMID:
25447171
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000543320.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces glycine with serine at codon 621 of the KCNQ1 protein (p.Gly621Ser). The glycine residue is weakly conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs199472820, ExAC <0.01%). This variant has been reported in an individual who experienced sudden cardiac death (PMID: 25447171). It has also been observed in an individual without a known history of arrhythmias (PMID: 14661677). ClinVar contains an entry for this variant (Variation ID: 67061). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). The serine amino acid residue is also found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this is a rare intronic change with uncertain impact on mRNA splicing. 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 25, 2021

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