NM_000527.5(LDLR):c.520G>A (p.Glu174Lys) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 22, 2022
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:: RCV002340781.2

Allele description [Variation Report for NM_000527.5(LDLR):c.520G>A (p.Glu174Lys)]

NM_000527.5(LDLR):c.520G>A (p.Glu174Lys)

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.520G>A (p.Glu174Lys)

HGVS:

NC_000019.10:g.11105426G>A
NG_009060.1:g.21046G>A
NM_000527.5:c.520G>AMANE SELECT
NM_001195798.2:c.520G>A
NM_001195799.2:c.397G>A
NM_001195800.2:c.314-1966G>A
NM_001195803.2:c.314-1139G>A
NP_000518.1:p.Glu174Lys
NP_000518.1:p.Glu174Lys
NP_001182727.1:p.Glu174Lys
NP_001182728.1:p.Glu133Lys
LRG_274t1:c.520G>A
LRG_274:g.21046G>A
LRG_274p1:p.Glu174Lys
NC_000019.9:g.11216102G>A
NM_000527.4:c.520G>A

Protein change:

E133K

Molecular consequence:

NM_001195800.2:c.314-1966G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001195803.2:c.314-1139G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000527.5:c.520G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.520G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.397G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002640579	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Sep 22, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002640579

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Sep 22, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Homozygous Familial Hypercholesterolemia in Spain: Prevalence and Phenotype-Genotype Relationship.

Sánchez-Hernández RM, Civeira F, Stef M, Perez-Calahorra S, Almagro F, Plana N, Novoa FJ, Sáenz-Aranzubía P, Mosquera D, Soler C, Fuentes FJ, Brito-Casillas Y, Real JT, Blanco-Vaca F, Ascaso JF, Pocovi M.

Circ Cardiovasc Genet. 2016 Dec;9(6):504-510. doi: 10.1161/CIRCGENETICS.116.001545. Epub 2016 Oct 26.

PubMed [citation]

PMID:: 27784735

Details of each submission

From Ambry Genetics, SCV002640579.2

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

Description

The p.E174K variant (also known as c.520G>A), located in coding exon 4 of the LDLR gene, results from a G to A substitution at nucleotide position 520. The glutamic acid at codon 174 is replaced by lysine, an amino acid with similar properties. This variant co-occurred with a mutation in the APOB gene in an individual from a homozygous familial hypercholesterolemia cohort; however, details were limited (Sánchez-Hernández RM et al. Circ Cardiovasc Genet, 2016 Dec;9:504-510). This amino acid position is poorly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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: Jul 23, 2024

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