NM_000527.5(LDLR):c.1729T>C (p.Trp577Arg) AND Cardiovascular phenotype

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 6, 2021
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:: RCV002411087.2

Allele description [Variation Report for NM_000527.5(LDLR):c.1729T>C (p.Trp577Arg)]

NM_000527.5(LDLR):c.1729T>C (p.Trp577Arg)

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.1729T>C (p.Trp577Arg)

Other names:

NP_000518.1:p.W577R

HGVS:

NC_000019.10:g.11116882T>C
NG_009060.1:g.32502T>C
NM_000527.5:c.1729T>CMANE SELECT
NM_001195798.2:c.1729T>C
NM_001195799.2:c.1606T>C
NM_001195800.2:c.1225T>C
NM_001195803.2:c.1348T>C
NP_000518.1:p.Trp577Arg
NP_000518.1:p.Trp577Arg
NP_001182727.1:p.Trp577Arg
NP_001182728.1:p.Trp536Arg
NP_001182729.1:p.Trp409Arg
NP_001182732.1:p.Trp450Arg
LRG_274t1:c.1729T>C
LRG_274:g.32502T>C
LRG_274p1:p.Trp577Arg
NC_000019.9:g.11227558T>C
NM_000527.4:c.1729T>C
c.1729T>C

Protein change:

W409R

Links:

LDLR-LOVD, British Heart Foundation: LDLR_000802; dbSNP: rs879255000

NCBI 1000 Genomes Browser:

rs879255000

Molecular consequence:

NM_000527.5:c.1729T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.1729T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.1606T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.1225T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.1348T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

Recent activity

Clear Turn Off Turn On

Historical Trauma
Historical Trauma

MedGen

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
SCV002716700	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Jul 6, 2021)	germline	clinical testing	PubMed (13) [See all records that cite these PMIDs] 11013454, 11810272, 12436241, 15199436, 15823276, 17347910, 18339137, 22081141, 22528129, 25378237, 27919346, 28126585, 29213121 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002716700

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Jul 6, 2021)

germline

clinical testing

PubMed (13)
[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

Homozygous familial hypercholesterolemia: A novel point mutation (W556R) in a Turkish patient.

Gutierrez G, Schneider A, Jobs J, Schmidt H, Korte A, Manns MP, Stuhrmann M.

Hum Mutat. 2000 Oct;16(4):374. No abstract available.

PubMed [citation]

PMID:: 11013454

The molecular basis of familial hypercholesterolemia in The Netherlands.

Fouchier SW, Defesche JC, Umans-Eckenhausen MW, Kastelein JP.

Hum Genet. 2001 Dec;109(6):602-15. Epub 2001 Nov 9.

PubMed [citation]

PMID:: 11810272

See all PubMed Citations (13)

Details of each submission

From Ambry Genetics, SCV002716700.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (13)

Description

The p.W577R pathogenic mutation (also known as c.1729T>C), located in coding exon 12 of the LDLR gene, results from a T to C substitution at nucleotide position 1729. The tryptophan at codon 577 is replaced by arginine, an amino acid with dissimilar properties. This alteration, also referred to as p.W556R, has been reported in both the homozygous and heterozygous states in multiple Turkish families with familial hypercholesterolemia (FH) and was found to segregate with the disease (Gutierrez G et al. Hum. Mutat., 2000 Oct;16:374; Sözen MM et al. Atherosclerosis, 2005 May;180:63-71; Schmidt HH et al. Clin Transplant, 2008 Mar-Apr;22:180-4; Schaefer JR et al. Clin Res Cardiol Suppl, 2012 Jun;7:2-6; Taylan C et al. J Clin Lipidol 2016 Aug;10:1303-1310). This alteration was also described in association with FH in other populations (Fouchier SW et al. Hum. Genet., 2001 Dec;109:602-15; Amsellem S et al. Hum. Genet., 2002 Dec;111:501-10; Leren TP et al. Semin Vasc Med, 2004 Feb;4:75-85; Widhalm K et al. J. Inherit. Metab. Dis., 2007 Apr;30:239-47; Fairoozy RH et al. Sci Rep, 2017 Dec;7:17087). Internal analysis has predicted that this alteration, located in the YWTD motif of LDLR class B report 5, disrupts the protein structure (Lo Surdo P et al. EMBO Rep., 2011 Dec;12:1300-5; Etxebarria A et al. Hum. Mutat., 2015 Jan;36:129-41). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

#	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

ClinVar

Relating variation to medicine