NM_000527.5(LDLR):c.514G>A (p.Asp172Asn) AND Cardiovascular phenotype

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Mar 9, 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:: RCV002338784.2

Allele description [Variation Report for NM_000527.5(LDLR):c.514G>A (p.Asp172Asn)]

NM_000527.5(LDLR):c.514G>A (p.Asp172Asn)

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.514G>A (p.Asp172Asn)

Other names:

NP_000518.1:p.D172N

HGVS:

NC_000019.10:g.11105420G>A
NG_009060.1:g.21040G>A
NM_000527.5:c.514G>AMANE SELECT
NM_001195798.2:c.514G>A
NM_001195799.2:c.391G>A
NM_001195800.2:c.314-1972G>A
NM_001195803.2:c.314-1145G>A
NP_000518.1:p.Asp172Asn
NP_000518.1:p.Asp172Asn
NP_001182727.1:p.Asp172Asn
NP_001182728.1:p.Asp131Asn
LRG_274t1:c.514G>A
LRG_274:g.21040G>A
LRG_274p1:p.Asp172Asn
NC_000019.9:g.11216096G>A
NM_000527.4:c.514G>A
P01130:p.Asp172Asn
c.514G>A
p.(Asp172Asn)

Protein change:

D131N

Links:

LDLR-LOVD, British Heart Foundation: LDLR_001751; UniProtKB: P01130#VAR_072832; dbSNP: rs879254554

NCBI 1000 Genomes Browser:

rs879254554

Molecular consequence:

NM_001195800.2:c.314-1972G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001195803.2:c.314-1145G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000527.5:c.514G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.514G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.391G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

Recent activity

Clear Turn Off Turn On

DPEP2 dipeptidase 2 [Gallus gallus]
DPEP2 dipeptidase 2 [Gallus gallus]
Gene ID:107054267

Gene

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
SCV002641057	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Mar 9, 2017)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 10532689, 15199436, 15241806, 16806138, 25545329 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002641057

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Mar 9, 2017)

germline

clinical testing

PubMed (5)
[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

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

Application of molecular genetics for diagnosing familial hypercholesterolemia in Norway: results from a family-based screening program.

Leren TP, Manshaus T, Skovholt U, Skodje T, Nossen IE, Teie C, Sørensen S, Bakken KS.

Semin Vasc Med. 2004 Feb;4(1):75-85. Review.

PubMed [citation]

PMID:: 15199436

See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV002641057.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

The p.D172N variant (also known as c.514G>A), located in coding exon 4 of the LDLR gene, results from a G to A substitution at nucleotide position 514. The aspartic acid at codon 172 is replaced by asparagine, an amino acid with highly similar properties. This alteration has been reported in multiple patients with familial hypercholesterolemia from different origins (Jensen HK et al. Atherosclerosis, 1999 Oct;146:337-44; Leren TP et al. Semin Vasc Med, 2004 Feb;4:75-85; Mozas P et al. Hum. Mutat., 2004 Aug;24:187; Chater R et al. Clin. Chim. Acta, 2006 Nov;373:62-9). This alteration was reported to segregate with the disease in the proband and three affected family members (Chater R et al. Clin. Chim. Acta, 2006 Nov;373:62-9). In vitro experiments suggested that this alteration resulted in deficient ligand binding while not affecting protein expression (Etxebarria A et al. Atherosclerosis, 2015 Feb;238:304-12). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

#	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: Oct 20, 2024

ClinVar

Relating variation to medicine