NM_172056.2(KCNH2):c.1805T>C (p.Leu602Pro) AND not specified

Clinical significance:Uncertain significance (Last evaluated: Dec 31, 2013)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000223929.1

Allele description [Variation Report for NM_172056.2(KCNH2):c.1805T>C (p.Leu602Pro)]

NM_172056.2(KCNH2):c.1805T>C (p.Leu602Pro)

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_172056.2(KCNH2):c.1805T>C (p.Leu602Pro)
HGVS:
  • NC_000007.14:g.150951588A>G
  • NG_008916.1:g.31339T>C
  • NM_000238.3:c.1805T>C
  • NM_001204798.2:c.785T>C
  • NM_172056.2:c.1805T>C
  • NM_172057.2:c.785T>C
  • NP_000229.1:p.Leu602Pro
  • NP_001191727.1:p.Leu262Pro
  • NP_742053.1:p.Leu602Pro
  • NP_742054.1:p.Leu262Pro
  • LRG_288t1:c.1805T>C
  • LRG_288t2:c.1805T>C
  • LRG_288t3:c.785T>C
  • LRG_288:g.31339T>C
  • LRG_288p1:p.Leu602Pro
  • LRG_288p2:p.Leu602Pro
  • LRG_288p3:p.Leu262Pro
  • NC_000007.13:g.150648676A>G
  • NM_000238.2:c.1805T>C
Protein change:
L262P
Links:
dbSNP: rs876661348
NCBI 1000 Genomes Browser:
rs876661348
Molecular consequence:
  • NM_000238.3:c.1805T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001204798.2:c.785T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172056.2:c.1805T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172057.2:c.785T>C - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000280120Stanford Center for Inherited Cardiovascular Disease, Stanford Universityno assertion criteria providedUncertain significance
(Dec 31, 2013)
germlineclinical testing

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided1not providednot providednot providednot providedclinical testing

Details of each submission

From Stanford Center for Inherited Cardiovascular Disease, Stanford University, SCV000280120.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided

Description

Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. KCNH2 p.Leu602Pro Based on the evidence reviewed below, we classify this variant as a variant of uncertain significance (VUS). The Leu602Pro variant in the KCNH2 gene is novel, and has not been previously reported as a disease-causing mutation nor as a benign polymorphism to our knowledge (after searches of PubMed and Google). Variation at several nearby residues has been associated with LQT2: I593R, I593T, I593G, I593X, P596L, P596R, G601S, G604S, D609N, D609H, D609G, Y611H, Y611X, V612L (UniProtKB; IRCCS Fondazione Salvatore Maugeri database). This is a conservative amino acid change, resulting in the replacement of a nonpolar leucine with a nonpolar proline. The leucine at this location varies in 9 of 32 mammalian species sequenced, and proline is the normal amino acid in stickleback fish. The adjacent residues similarly vary across species. In silico analysis with PolyPhen-2 (http://genetics.bwh.harvard.edu/pph2/) predicts the variant to be “benign”. In total the variant has not been seen in >5330 individuals from publicly available population datasets. This variant is not listed in the NHLBI Exome Sequencing Project dataset (http://evs.gs.washington.edu/EVS/), which currently includes variant calls on ~3500 Caucasian and ~1800 African American individuals. There is no variation at this codon listed in dbSNP (http://www.ncbi.nlm.nih.gov/projects/SNP) or 1000 genomes (http://browser.1000genomes.org/index.htm), as of May 13, 2012.

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

Last Updated: Sep 23, 2021

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