NM_000527.5(LDLR):c.1510A>G (p.Lys504Glu) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 13, 2024
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:: RCV004629153.1

Allele description [Variation Report for NM_000527.5(LDLR):c.1510A>G (p.Lys504Glu)]

NM_000527.5(LDLR):c.1510A>G (p.Lys504Glu)

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.1510A>G (p.Lys504Glu)

HGVS:

NC_000019.10:g.11113686A>G
NG_009060.1:g.29306A>G
NM_000527.5:c.1510A>GMANE SELECT
NM_001195798.2:c.1510A>G
NM_001195799.2:c.1387A>G
NM_001195800.2:c.1006A>G
NM_001195803.2:c.1129A>G
NP_000518.1:p.Lys504Glu
NP_000518.1:p.Lys504Glu
NP_001182727.1:p.Lys504Glu
NP_001182728.1:p.Lys463Glu
NP_001182729.1:p.Lys336Glu
NP_001182732.1:p.Lys377Glu
LRG_274t1:c.1510A>G
LRG_274:g.29306A>G
NC_000019.9:g.11224362A>G
NM_000527.4(LDLR):c.1510A>G
NM_000527.4:c.1510A>G
c.1510A>G

Protein change:

K336E

Links:

LDLR-LOVD, British Heart Foundation: LDLR_001446; dbSNP: rs730882103

NCBI 1000 Genomes Browser:

rs730882103

Molecular consequence:

NM_000527.5:c.1510A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.1510A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.1387A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.1006A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.1129A>G - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

no known functional consequence - Comment(s)

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
SCV005135989	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Jun 13, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 15199436, 19318025, 27784735 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005135989

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Jun 13, 2024)

germline

clinical testing

PubMed (3)
[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

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

Genetic diagnosis of familial hypercholesterolemia using a DNA-array based platform.

Alonso R, Defesche JC, Tejedor D, Castillo S, Stef M, Mata N, Gomez-Enterria P, Martinez-Faedo C, Forga L, Mata P.

Clin Biochem. 2009 Jun;42(9):899-903. doi: 10.1016/j.clinbiochem.2009.01.017. Epub 2009 Feb 6.

PubMed [citation]

PMID:: 19318025

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV005135989.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The p.K504E variant (also known as c.1510A>G), located in coding exon 10 of the LDLR gene, results from an A to G substitution at nucleotide position 1510. The lysine at codon 504 is replaced by glutamic acid, an amino acid with similar properties. This alteration has been reported in familial hypercholesterolemia (FH) cohorts (Leren TP et al. Semin Vasc Med, 2004 Feb;4:75-85; Alonso R et al. Clin Biochem, 2009 Jun;42:899-903; 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. Based on the available evidence, the clinical significance of this variant 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: May 16, 2025

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