NM_000527.5(LDLR):c.1529C>T (p.Thr510Met) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 10, 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:: RCV002401935.2

Allele description [Variation Report for NM_000527.5(LDLR):c.1529C>T (p.Thr510Met)]

NM_000527.5(LDLR):c.1529C>T (p.Thr510Met)

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.1529C>T (p.Thr510Met)

HGVS:

NC_000019.10:g.11113705C>T
NG_009060.1:g.29325C>T
NM_000527.5:c.1529C>TMANE SELECT
NM_001195798.2:c.1529C>T
NM_001195799.2:c.1406C>T
NM_001195800.2:c.1025C>T
NM_001195803.2:c.1148C>T
NP_000518.1:p.Thr510Met
NP_000518.1:p.Thr510Met
NP_001182727.1:p.Thr510Met
NP_001182728.1:p.Thr469Met
NP_001182729.1:p.Thr342Met
NP_001182732.1:p.Thr383Met
LRG_274t1:c.1529C>T
LRG_274:g.29325C>T
NC_000019.9:g.11224381C>T
NM_000527.4(LDLR):c.1529C>T
NM_000527.4:c.1529C>T
c.1529C>T

Protein change:

T342M

Links:

LDLR-LOVD, British Heart Foundation: LDLR_000900; dbSNP: rs755154048

NCBI 1000 Genomes Browser:

rs755154048

Molecular consequence:

NM_000527.5:c.1529C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.1529C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.1406C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.1025C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.1148C>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
SCV002708239	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Jun 10, 2022)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 10947889, 15199436, 16542394, 22698793, 32660911, 32770674, 33303402 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002708239

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Jun 10, 2022)

germline

clinical testing

PubMed (7)
[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

Cardiovascular risk factors and testing of relatives amongst patients with familial hyperlipidaemia one decade after a clinical trial.

Tonstad S, Hjermann I.

J Intern Med. 2000 Aug;248(2):111-8.

PubMed [citation]

PMID:: 10947889

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 (7)

Details of each submission

From Ambry Genetics, SCV002708239.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

The p.T510M variant (also known as c.1529C>T), located in coding exon 10 of the LDLR gene, results from a C to T substitution at nucleotide position 1529. The threonine at codon 510 is replaced by methionine, an amino acid with similar properties. This alteration, which is also known as p.T489M, has been reported in several familial hypercholesterolemia (FH) cohorts; however, clinical details were limited (Tonstad S et al. J Intern Med, 2000 Aug;248:111-8; Brusgaard K et al. Clin Genet, 2006 Mar;69:277-83; Tichý L et al. Atherosclerosis, 2012 Aug;223:401-8; Lamiquiz-Moneo I et al. Rev Esp Cardiol (Engl Ed), 2021 Aug;74:664-673; Rieck L et al. Clin Genet, 2020 11;98:457-467). This amino acid position is well 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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