NM_000527.5(LDLR):c.681C>A (p.Asp227Glu) AND Cardiovascular phenotype

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 26, 2021
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:: RCV002365580.2

Allele description [Variation Report for NM_000527.5(LDLR):c.681C>A (p.Asp227Glu)]

NM_000527.5(LDLR):c.681C>A (p.Asp227Glu)

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.681C>A (p.Asp227Glu)

HGVS:

NC_000019.10:g.11105587C>A
NG_009060.1:g.21207C>A
NM_000527.5:c.681C>AMANE SELECT
NM_001195798.2:c.681C>A
NM_001195799.2:c.558C>A
NM_001195800.2:c.314-1805C>A
NM_001195803.2:c.314-978C>A
NP_000518.1:p.Asp227Glu
NP_000518.1:p.Asp227Glu
NP_001182727.1:p.Asp227Glu
NP_001182728.1:p.Asp186Glu
LRG_274t1:c.681C>A
LRG_274:g.21207C>A
LRG_274p1:p.Asp227Glu
NC_000019.9:g.11216263C>A
NM_000527.4:c.681C>A

Protein change:

D186E

Links:

dbSNP: rs121908028

NCBI 1000 Genomes Browser:

rs121908028

Molecular consequence:

NM_001195800.2:c.314-1805C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001195803.2:c.314-978C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000527.5:c.681C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.681C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.558C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002664174	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (May 26, 2021)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 17087781, 22698793, 22883975, 26748104, 27578117, 27680772, 27919364, 31491741 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002664174

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(May 26, 2021)

germline

clinical testing

PubMed (8)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Identification and characterization of novel low-density lipoprotein receptor mutations of familial hypercholesterolaemia patients in Taiwan.

Charng MJ, Chiou KR, Chang HM, Cheng HM, Ye ZX, Lin SJ.

Eur J Clin Invest. 2006 Dec;36(12):866-74.

PubMed [citation]

PMID:: 17087781

The molecular basis of familial hypercholesterolemia in the Czech Republic: spectrum of LDLR mutations and genotype-phenotype correlations.

Tichý L, Freiberger T, Zapletalová P, Soška V, Ravčuková B, Fajkusová L.

Atherosclerosis. 2012 Aug;223(2):401-8. doi: 10.1016/j.atherosclerosis.2012.05.014. Epub 2012 May 23.

PubMed [citation]

PMID:: 22698793

See all PubMed Citations (8)

Details of each submission

From Ambry Genetics, SCV002664174.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

The p.D227E pathogenic mutation (also known as c.681C>A), located in coding exon 4 of the LDLR gene, results from a C to A substitution at nucleotide position 681. The aspartic acid at codon 227 is replaced by glutamic acid, an amino acid with highly similar properties. This alteration, which is also known as p.D206E, has been reported in familial hypercholesterolemia (FH) cohorts in both the heterozygous and homozygous states (Charng MJ et al. Eur J Clin Invest, 2006 Dec;36:866-74; Hooper AJ et al. Atherosclerosis, 2012 Oct;224:430-4; Reiman A et al. Ann Clin Biochem, 2016 Nov;53:654-662; Hori M et al. Atherosclerosis, 2019 10;289:101-108). In addition, a different alteration located at the same position, resulting in the same protein change, c.681C>G (p.D227E), is a founder mutation that accounts for the majority of FH in the Afrikaner population (Leitersdorf et al. J Clin Invest.1989;84(3):954-61; King et al. N Z Med J. 2010;123(1319):79-82) and had also been reported in affected individuals of multiple ethnicities (Gudnason et al. Arterioscler. Thromb. 1993;13(1):56-63; Leren et al. Semin Vasc Med. 2004;4(1):75-85; Bertolini et al Atherosclerosis 2013;227(2):342-348; Sharifi et al. Metab. Clin. Exp. 2016;65(3):48-53). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 13, 2025

ClinVar

Relating variation to medicine