NM_000238.4(KCNH2):c.2863C>G (p.Leu955Val) AND not provided

Clinical significance:Conflicting interpretations of pathogenicity, Likely pathogenic(1);Uncertain significance(1) (Last evaluated: Sep 4, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000413036.2

Allele description [Variation Report for NM_000238.4(KCNH2):c.2863C>G (p.Leu955Val)]

NM_000238.4(KCNH2):c.2863C>G (p.Leu955Val)

Gene:
KCNH2:potassium voltage-gated channel subfamily H member 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7q36.1
Genomic location:
Preferred name:
NM_000238.4(KCNH2):c.2863C>G (p.Leu955Val)
HGVS:
  • NC_000007.14:g.150947708G>C
  • NG_008916.1:g.35219C>G
  • NM_000238.3:c.2863C>G
  • NM_000238.4:c.2863C>GMANE SELECT
  • NM_172057.2:c.1843C>G
  • NM_172057.3:c.1843C>G
  • NP_000229.1:p.Leu955Val
  • NP_000229.1:p.Leu955Val
  • NP_742054.1:p.Leu615Val
  • NP_742054.1:p.Leu615Val
  • LRG_288t1:c.2863C>G
  • LRG_288t3:c.1843C>G
  • LRG_288:g.35219C>G
  • LRG_288p1:p.Leu955Val
  • LRG_288p3:p.Leu615Val
  • NC_000007.13:g.150644796G>C
  • NC_000007.13:g.150644796G>C
  • NM_000238.2:c.2863C>G
Protein change:
L615V
Links:
dbSNP: rs199473012
NCBI 1000 Genomes Browser:
rs199473012
Molecular consequence:
  • NM_000238.3:c.2863C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000238.4:c.2863C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172057.2:c.1843C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172057.3:c.1843C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000491005GeneDxcriteria provided, single submitter
Uncertain significance
(Sep 4, 2019)
germlineclinical testing

Citation Link,

SCV000884047ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratoriescriteria provided, single submitter
Likely pathogenic
(Nov 6, 2017)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From GeneDx, SCV000491005.1

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

Description

Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Reported in ClinVar (ClinVar Variant ID# 67445; Landrum et al., 2016); Functional studies conducted using CHO and HEK cells demonstrated that the L955V variant led to a defect of protein trafficking, resulting in greatly reduced ion current in the plasma membrane (Biliczki et al., 2008); nevertheless, it is unclear how these studies may translate to a pathogenic role in vivo; In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 18675227, 22581653, 33258288)

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

From ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories, SCV000884047.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 25, 2021

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