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NM_000527.5(LDLR):c.418G>A (p.Glu140Lys) AND Cardiovascular phenotype

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 27, 2017
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:
RCV002327170.3

Allele description [Variation Report for NM_000527.5(LDLR):c.418G>A (p.Glu140Lys)]

NM_000527.5(LDLR):c.418G>A (p.Glu140Lys)

Gene:
LDLR:low density lipoprotein receptor [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19p13.2
Genomic location:
Preferred name:
NM_000527.5(LDLR):c.418G>A (p.Glu140Lys)
Other names:
FH Philippines; FH Durban-2; NP_000518.1:p.E140K; NM_000527.5(LDLR):c.418G>A
HGVS:
  • NC_000019.10:g.11105324G>A
  • NG_009060.1:g.20944G>A
  • NM_000527.5:c.418G>AMANE SELECT
  • NM_001195798.2:c.418G>A
  • NM_001195799.2:c.295G>A
  • NM_001195800.2:c.314-2068G>A
  • NM_001195803.2:c.314-1241G>A
  • NP_000518.1:p.Glu140Lys
  • NP_000518.1:p.Glu140Lys
  • NP_001182727.1:p.Glu140Lys
  • NP_001182728.1:p.Glu99Lys
  • LRG_274t1:c.418G>A
  • LRG_274:g.20944G>A
  • LRG_274p1:p.Glu140Lys
  • NC_000019.9:g.11216000G>A
  • NM_000527.4:c.418G>A
  • P01130:p.Glu140Lys
  • c.418G>A
Protein change:
E140K
Links:
LDLR-LOVD, British Heart Foundation: LDLR_001730; UniProtKB: P01130#VAR_005318
Molecular consequence:
  • NM_001195800.2:c.314-2068G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001195803.2:c.314-1241G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000527.5:c.418G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.418G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195799.2:c.295G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002626623Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Nov 27, 2017) 		germlineclinical testing

PubMed (11)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Spectrum of LDL receptor gene mutations in Denmark: implications for molecular diagnostic strategy in heterozygous familial hypercholesterolemia.

Jensen HK, Jensen LG, Meinertz H, Hansen PS, Gregersen N, Faergeman O.

Atherosclerosis. 1999 Oct;146(2):337-44.

PubMed [citation]
PMID:
10532689

Molecular genetics of familial hypercholesterolemia in Spain: Ten novel LDLR mutations and population analysis.

García-García AB, Real JT, Puig O, Cebolla E, Marín-García P, Martínez Ferrandis JI, García-Sogo M, Civera M, Ascaso JF, Carmena R, Armengod ME, Chaves FJ.

Hum Mutat. 2001 Nov;18(5):458-9.

PubMed [citation]
PMID:
11668640
See all PubMed Citations (11)

Details of each submission

From Ambry Genetics, SCV002626623.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (11)

Description

The p.E140K pathogenic mutation (also known as c.418G>A), located in coding exon 4 of the LDLR gene, results from a G to A substitution at nucleotide position 418. The glutamic acid at codon 140 is replaced by lysine, an amino acid with similar properties. This alteration, also referred to as E119K, has been reported in a number of individuals with familial hypercholesterolemia (FH) around the world (Hobbs HH et al. Hum. Mutat., 1992;1:445-66; Rubinsztein DC et al. Biochim. Biophys. Acta, 1993 Aug;1182:75-82; Maruyama T et al. Arterioscler. Thromb. Vasc. Biol., 1995 Oct;15:1713-8; Jensen HK et al. Atherosclerosis, 1999 Oct;146:337-44; García-García AB et al. Hum. Mutat., 2001 Nov;18:458-9; Vaca G et al. Atherosclerosis, 2011 Oct;218:391-6; Bertolini S et al. Atherosclerosis, 2013 Apr;227:342-8; Shin DG et al. Atherosclerosis, 2015 Nov;243:53-8). Alterations affecting the same amino acid residue, E140D, E140G and E140A, have also been reported in association with FH (Fouchier SW et al. Hum. Genet., 2001 Dec;109:602-15; Kuhrová V et al. Hum. Mutat., 2002 Jan;19:80; Durst R et al. Atherosclerosis, 2017 Feb;257:55-63). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Sep 29, 2024