NM_000238.4(KCNH2):c.1847A>G (p.Tyr616Cys) AND not provided

Clinical significance:Pathogenic (Last evaluated: Apr 12, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_000238.4(KCNH2):c.1847A>G (p.Tyr616Cys)]

NM_000238.4(KCNH2):c.1847A>G (p.Tyr616Cys)

KCNH2:potassium voltage-gated channel subfamily H member 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_000238.4(KCNH2):c.1847A>G (p.Tyr616Cys)
Other names:
  • NC_000007.14:g.150951546T>C
  • NG_008916.1:g.31381A>G
  • NM_000238.3:c.1847A>G
  • NM_000238.4:c.1847A>GMANE SELECT
  • NM_001204798.2:c.827A>G
  • NM_172056.2:c.1847A>G
  • NM_172057.3:c.827A>G
  • NP_000229.1:p.Tyr616Cys
  • NP_000229.1:p.Tyr616Cys
  • NP_001191727.1:p.Tyr276Cys
  • NP_742053.1:p.Tyr616Cys
  • NP_742054.1:p.Tyr276Cys
  • LRG_288t1:c.1847A>G
  • LRG_288t2:c.1847A>G
  • LRG_288:g.31381A>G
  • LRG_288p1:p.Tyr616Cys
  • LRG_288p2:p.Tyr616Cys
  • NC_000007.13:g.150648634T>C
  • NM_000238.2:c.1847A>G
  • Q12809:p.Tyr616Cys
Protein change:
UniProtKB: Q12809#VAR_074849; dbSNP: rs199472946
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000238.3:c.1847A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000238.4:c.1847A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001204798.2:c.827A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172056.2:c.1847A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172057.3:c.827A>G - missense variant - [Sequence Ontology: SO:0001583]


MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000234335GeneDxcriteria provided, single submitter
(Apr 12, 2019)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From GeneDx, SCV000234335.8

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided


Observed in individuals with LQTS referred for genetic testing at Genedx and in the published literature (Kapplinger et al., 2009); Not observed in large population cohorts (Lek et al., 2016); Published functional studies demonstrate Y616C generated minimal current, suggesting altered channel permeability as a mechanism that leads to loss of function (Anderson et al., 2014); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Reported in ClinVar as a likely pathogenic variant (ClinVar Variant ID 67295; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 19716085, 25417810)

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 25, 2021

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