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NM_000218.3(KCNQ1):c.1591-1G>A AND Congenital long QT syndrome

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Mar 23, 2018
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000825532.5

Allele description [Variation Report for NM_000218.3(KCNQ1):c.1591-1G>A]

NM_000218.3(KCNQ1):c.1591-1G>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.1591-1G>A
HGVS:
  • NC_000011.10:g.2775959G>A
  • NG_008935.1:g.335969G>A
  • NM_000218.3:c.1591-1G>AMANE SELECT
  • NM_001406836.1:c.1495-1G>A
  • NM_001406837.1:c.1321-1G>A
  • NM_001406838.1:c.1051-1G>A
  • NM_181798.2:c.1210-1G>A
  • LRG_287t1:c.1591-1G>A
  • LRG_287:g.335969G>A
  • NC_000011.9:g.2797189G>A
  • NM_000218.2:c.1591-1G>A
Links:
dbSNP: rs1590081328
NCBI 1000 Genomes Browser:
rs1590081328
Molecular consequence:
  • NM_000218.3:c.1591-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406836.1:c.1495-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406837.1:c.1321-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406838.1:c.1051-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_181798.2:c.1210-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
Observations:
2

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

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000966847Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)		Likely pathogenic
(Mar 23, 2018) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided22not 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, Mass General Brigham Personalized Medicine, SCV000966847.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testing PubMed (1)

Description

The c.1591-1G>A variant in KCNQ1 has not been previously reported in individuals with long QT syndrome or in large population studies. This variant occurs in th e invariant region (+/- 1,2) of the splice consensus sequence and is predicted t o cause altered splicing leading to an abnormal or absent protein. Loss-of-funct ion variants in KCNQ1 are associated with LQTS (also known as Romano-Ward syndro me) in the heterozygous state and with Jervell and Lange-Nielsen syndrome (JLNS) in the compound heterozygous or homozygous state. In summary, although addition al studies are required to fully establish its clinical significance, the c.1591 -1G>A variant is likely pathogenic. ACMG Criteria applied (Richards 2015): PM2; PVS1_Strong.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided2not provided2not provided

Last Updated: Feb 28, 2024