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NM_000218.3(KCNQ1):c.1486_1487del (p.Leu496fs) AND KCNQ1-related epilepsy

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jul 2, 2021
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:
RCV001838979.10

Allele description [Variation Report for NM_000218.3(KCNQ1):c.1486_1487del (p.Leu496fs)]

NM_000218.3(KCNQ1):c.1486_1487del (p.Leu496fs)

Genes:
KCNQ1OT1:KCNQ1 opposite strand/antisense transcript 1 [Gene - OMIM - HGNC]
KCNQ1:potassium voltage-gated channel subfamily Q member 1 [Gene - OMIM - HGNC]
Variant type:
Microsatellite
Cytogenetic location:
11p15.5
Genomic location:
Preferred name:
NM_000218.3(KCNQ1):c.1486_1487del (p.Leu496fs)
HGVS:
  • NC_000011.10:g.2662051CT[1]
  • NG_008935.1:g.222061CT[1]
  • NG_016178.2:g.42945AG[1]
  • NM_000218.3:c.1486_1487delMANE SELECT
  • NM_001406836.1:c.1390_1391del
  • NM_001406837.1:c.1216_1217del
  • NM_001406838.1:c.946_947del
  • NM_181798.2:c.1105_1106del
  • NP_000209.2:p.Leu496Alafs
  • NP_000209.2:p.Leu496fs
  • NP_001393765.1:p.Leu464fs
  • NP_001393766.1:p.Leu406fs
  • NP_001393767.1:p.Leu316fs
  • NP_861463.1:p.Leu369Alafs
  • NP_861463.1:p.Leu369fs
  • LRG_1052t1:n.37945AG[1]
  • LRG_287t1:c.1484_1485CT[1]
  • LRG_287t2:c.1103_1104CT[1]
  • LRG_1052:g.42945AG[1]
  • LRG_287:g.222061CT[1]
  • LRG_287p1:p.Leu496Alafs
  • LRG_287p2:p.Leu369Alafs
  • NC_000011.9:g.2683281CT[1]
  • NC_000011.9:g.2683281_2683282del
  • NM_000218.2:c.1484_1485CT[1]
  • NM_000218.2:c.1486_1487del
  • NM_000218.2:c.1486_1487del
  • NM_000218.2:c.1486_1487delCT
  • NM_181798.1:c.1103_1104CT[1]
  • NR_002728.3:n.37945AG[1]
  • NR_002728.4:n.37941_37942AG[1]
  • NR_040711.2:n.1377_1378CT[1]
Protein change:
L316fs
Links:
dbSNP: rs397508090
NCBI 1000 Genomes Browser:
rs397508090
Molecular consequence:
  • NM_000218.3:c.1486_1487del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001406836.1:c.1390_1391del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001406837.1:c.1216_1217del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001406838.1:c.946_947del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_181798.2:c.1105_1106del - frameshift variant - [Sequence Ontology: SO:0001589]
Observations:
1

Condition(s)

Name:
KCNQ1-related epilepsy
Identifiers:

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV002099018New York Genome Center - CSER-NYCKidSeq
criteria provided, single submitter

(NYGC Assertion Criteria 2020)
Uncertain significance
(Jul 2, 2021)
inheritedclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedinheritedunknown1not providednot provided1not providedclinical testing

Details of each submission

From New York Genome Center - CSER-NYCKidSeq, SCV002099018.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided

Description

The inherited heterozygous two nucleotide deletion [c.1486_1487del (p.Leu496AlafsTer19)] identified in exon 11 (of 16) of the KCNQ1 gene alters the wild-type translational reading frame and is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The variant has been reported in multiple individuals affected with LQTS and JLNS [PMID: 16414944, 27917693, 24372464, 28438721]. It was reported as homozygous and co-segregated with JLNS in two Saudi Arabian families [PMID: 24372464, 28438721]. In both families, individuals homozygous for this variant as well as several heterozygous carriers had LQTS. Additionally, this variant has been reported in compound heterozygosity with the c.683 + 5 G>A variant in a Chinese family affected with JLNS [PMID: 27917693]. Seizures were not reported in any individual in these studies carrying the c.1486_1487del (p.Leu496AlafsTer19) variant. The variant has been reported as Pathogenic in ClinVar database [Variation ID: 52983, phenotypic condition not provided]. The variant is absent from gnomAD(v3) database suggesting it is not a common benign variant in the populations represented in that database. Based on the available evidence, although pathogenic for LQTS and JLNS, the inherited c.1486_1487del (p.Leu496AlafsTer19)] variant is reported as a Variant of Uncertain Significance in a Gene of Unknown Significance for epilepsy phenotype.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1inheritedunknown1not providednot provided1not providednot providednot provided

Last Updated: Jul 15, 2024