NM_000527.5(LDLR):c.1574A>T (p.Asp525Val) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 17, 2023
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:: RCV003298317.2

Allele description [Variation Report for NM_000527.5(LDLR):c.1574A>T (p.Asp525Val)]

NM_000527.5(LDLR):c.1574A>T (p.Asp525Val)

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.1574A>T (p.Asp525Val)

HGVS:

NC_000019.10:g.11113750A>T
NG_009060.1:g.29370A>T
NM_000527.5:c.1574A>TMANE SELECT
NM_001195798.2:c.1574A>T
NM_001195799.2:c.1451A>T
NM_001195800.2:c.1070A>T
NM_001195803.2:c.1193A>T
NP_000518.1:p.Asp525Val
NP_000518.1:p.Asp525Val
NP_001182727.1:p.Asp525Val
NP_001182728.1:p.Asp484Val
NP_001182729.1:p.Asp357Val
NP_001182732.1:p.Asp398Val
LRG_274t1:c.1574A>T
LRG_274:g.29370A>T
LRG_274p1:p.Asp525Val
NC_000019.9:g.11224426A>T
NM_000527.4:c.1574A>T
c.1574A>T
p.(Asp525Val)

Protein change:

D357V

Links:

LDLR-LOVD, British Heart Foundation: LDLR_000739; dbSNP: rs879254943

NCBI 1000 Genomes Browser:

rs879254943

Molecular consequence:

NM_000527.5:c.1574A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.1574A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.1451A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.1070A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.1193A>T - 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
SCV004000128	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Apr 17, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 11857755, 15556094, 16389549, 20236128, 34297352 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004000128

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Apr 17, 2023)

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

Comparison of SSCP and DHPLC for the detection of LDLR mutations in a New Zealand cohort.

Bunn CF, Lintott CJ, Scott RS, George PM.

Hum Mutat. 2002 Mar;19(3):311.

PubMed [citation]

PMID:: 11857755

Genetic screening of patients with familial hypercholesterolaemia (FH): a New Zealand perspective.

Laurie AD, Scott RS, George PM.

Atheroscler Suppl. 2004 Dec;5(5):13-5.

PubMed [citation]

PMID:: 15556094

See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV004000128.2

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

Description

The p.D525V variant (also known as c.1574A>T), located in coding exon 10 of the LDLR gene, results from an A to T substitution at nucleotide position 1574. The aspartic acid at codon 525 is replaced by valine, an amino acid with highly dissimilar properties. This alteration (also noted as p.D504V) has been reported in association with familial hypercholesterolemia (FH) (Bunn CF et al. Hum Mutat, 2002 Mar;19:311; Humphries SE et al. J Mol Med (Berl), 2006 Mar;84:203-14; Di Taranto MD et al. Clin Genet, 2021 Nov;100:529-541). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. 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: Sep 29, 2024

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