NM_000218.3(KCNQ1):c.683+1G>A AND Congenital long QT syndrome

Clinical significance:Likely pathogenic (Last evaluated: Sep 8, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000825588.1

Allele description [Variation Report for NM_000218.3(KCNQ1):c.683+1G>A]

NM_000218.3(KCNQ1):c.683+1G>A

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_000218.3(KCNQ1):c.683+1G>A
HGVS:
  • NC_000011.10:g.2571404G>A
  • NG_008935.1:g.131414G>A
  • NM_000218.2:c.683+1G>A
  • NM_000218.3:c.683+1G>AMANE SELECT
  • NM_181798.1:c.302+1G>A
  • LRG_287t1:c.683+1G>A
  • LRG_287t2:c.302+1G>A
  • LRG_287:g.131414G>A
  • NC_000011.9:g.2592634G>A
  • NC_000011.9:g.2592634G>A
Links:
dbSNP: rs1589957233
NCBI 1000 Genomes Browser:
rs1589957233
Molecular consequence:
  • NM_000218.2:c.683+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_000218.3:c.683+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_181798.1:c.302+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
Observations:
1

Condition(s)

Name:
Congenital long QT syndrome (RWS)
Synonyms:
Familial long QT syndrome; Romano-Ward syndrome; Ventricular fibrillation with prolonged QT interval
Identifiers:
MONDO: MONDO:0019171; MedGen: C1141890; Orphanet: 768; OMIM: PS192500

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000966930Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicinecriteria provided, single submitter
Likely pathogenic
(Sep 8, 2017)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided11not providednot providednot providedclinical testing

Citations

PubMed

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]
PMID:
24033266
PMCID:
PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, SCV000966930.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

The c.683+1G>A variant in KCNQ1 has not been previously reported in individuals with long QT syndrome or in large population studies. This variant occurs in the invariant region (+/- 1,2) of the splice consensus sequence and is predicted to cause altered splicing leading to an abnormal or absent protein. Loss-of-functi on variants in KCNQ1 are associated with LQTS (also known as Romano-Ward syndrom e) in the heterozygous state and with Jervell and Lange-Nielsen syndrome (JLNS) in the compound heterozygous or homozygous state. In summary, although additiona l studies are required to fully establish its clinical significance, the c.683+1 G>A variant is likely pathogenic. ACMG/AMP criteria applied: PVS1, PM2.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided1not provided1not provided

Last Updated: Oct 25, 2021

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