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NM_000238.4(KCNH2):c.2000dup (p.Tyr667Ter) AND Long QT syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 4, 2016
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:
RCV000457192.9

Allele description [Variation Report for NM_000238.4(KCNH2):c.2000dup (p.Tyr667Ter)]

NM_000238.4(KCNH2):c.2000dup (p.Tyr667Ter)

Gene:
KCNH2:potassium voltage-gated channel subfamily H member 2 [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
7q36.1
Genomic location:
Preferred name:
NM_000238.4(KCNH2):c.2000dup (p.Tyr667Ter)
HGVS:
  • NC_000007.14:g.150951066dup
  • NG_008916.1:g.31861dup
  • NM_000238.4:c.2000dupMANE SELECT
  • NM_001204798.2:c.980dup
  • NM_001406753.1:c.1712dup
  • NM_001406755.1:c.1823dup
  • NM_001406756.1:c.1712dup
  • NM_001406757.1:c.1700dup
  • NM_172056.3:c.2000dup
  • NM_172057.3:c.980dup
  • NP_000229.1:p.Tyr667Ter
  • NP_000229.1:p.Tyr667Terfs
  • NP_001191727.1:p.Tyr327Ter
  • NP_001393682.1:p.Tyr571Terfs
  • NP_001393684.1:p.Tyr608Terfs
  • NP_001393685.1:p.Tyr571Terfs
  • NP_001393686.1:p.Tyr567Terfs
  • NP_742053.1:p.Tyr667Ter
  • NP_742053.1:p.Tyr667Terfs
  • NP_742054.1:p.Tyr327Ter
  • NP_742054.1:p.Tyr327Terfs
  • LRG_288t1:c.2000dup
  • LRG_288t2:c.2000dup
  • LRG_288t3:c.980dup
  • LRG_288:g.31861dup
  • LRG_288p1:p.Tyr667Terfs
  • LRG_288p2:p.Tyr667Ter
  • LRG_288p3:p.Tyr327Terfs
  • NC_000007.13:g.150648153_150648154insT
  • NC_000007.13:g.150648154dup
  • NM_000238.3:c.2000dup
  • NM_000238.3:c.2000dupA
  • NM_172056.2:c.2000dup
  • NM_172057.2:c.980dup
  • NR_176254.1:n.2408dup
  • NR_176255.1:n.1281dup
Protein change:
Y327*
Links:
dbSNP: rs1554425527
NCBI 1000 Genomes Browser:
rs1554425527
Molecular consequence:
  • NM_001406753.1:c.1712dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001406755.1:c.1823dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001406756.1:c.1712dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001406757.1:c.1700dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_172056.3:c.2000dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_000238.4:c.2000dup - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001204798.2:c.980dup - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001406753.1:c.1712dup - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001406755.1:c.1823dup - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001406756.1:c.1712dup - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001406757.1:c.1700dup - nonsense - [Sequence Ontology: SO:0001587]
  • NM_172056.3:c.2000dup - nonsense - [Sequence Ontology: SO:0001587]
  • NM_172057.3:c.980dup - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Long QT syndrome (LQTS)
Identifiers:
MONDO: MONDO:0002442; MeSH: D008133; MedGen: C0023976

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000543430Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jun 4, 2016) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

The genetic basis of long QT and short QT syndromes: a mutation update.

Hedley PL, Jørgensen P, Schlamowitz S, Wangari R, Moolman-Smook J, Brink PA, Kanters JK, Corfield VA, Christiansen M.

Hum Mutat. 2009 Nov;30(11):1486-511. doi: 10.1002/humu.21106. Review.

PubMed [citation]
PMID:
19862833

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000543430.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

While this particular variant has not been reported in the literature, truncating variants in KCNH2 are known to be pathogenic (PMID: 19862833). This sequence change inserts 1 nucleotide in exon 8 of the KCNH2 mRNA (c.2000dupA), causing a frameshift at codon 667. This creates a premature translational stop signal (p.Tyr667*) and is expected to result in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024