NM_000527.5(LDLR):c.1720C>T (p.Arg574Cys) AND Cardiovascular phenotype

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Feb 26, 2020
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:
RCV002399590.3

Allele description [Variation Report for NM_000527.5(LDLR):c.1720C>T (p.Arg574Cys)]

NM_000527.5(LDLR):c.1720C>T (p.Arg574Cys)

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.1720C>T (p.Arg574Cys)
Other names:
NM_000527.5(LDLR):c.1720C>T
HGVS:
  • NC_000019.10:g.11116873C>T
  • NG_009060.1:g.32493C>T
  • NM_000527.5:c.1720C>TMANE SELECT
  • NM_001195798.2:c.1720C>T
  • NM_001195799.2:c.1597C>T
  • NM_001195800.2:c.1216C>T
  • NM_001195803.2:c.1339C>T
  • NP_000518.1:p.Arg574Cys
  • NP_000518.1:p.Arg574Cys
  • NP_001182727.1:p.Arg574Cys
  • NP_001182728.1:p.Arg533Cys
  • NP_001182729.1:p.Arg406Cys
  • NP_001182732.1:p.Arg447Cys
  • LRG_274t1:c.1720C>T
  • LRG_274:g.32493C>T
  • NC_000019.9:g.11227549C>T
  • NM_000527.4(LDLR):c.1720C>T
  • NM_000527.4:c.1720C>T
  • P01130:p.Arg574Cys
  • c.1720C>T
  • p.(Arg574Cys)
Protein change:
R406C
Links:
LDLR-LOVD, British Heart Foundation: LDLR_000232; UniProtKB: P01130#VAR_072851; dbSNP: rs185098634
NCBI 1000 Genomes Browser:
rs185098634
Molecular consequence:
  • NM_000527.5:c.1720C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.1720C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195799.2:c.1597C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195800.2:c.1216C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195803.2:c.1339C>T - missense variant - [Sequence Ontology: SO:0001583]
Functional consequence:
no known functional consequence - Comment(s)

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002713634Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(Feb 26, 2020) 		germlineclinical testing

PubMed (8)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Identification of recurrent and novel mutations in the LDL receptor gene in German patients with familial hypercholesterolemia.

Nauck MS, Köster W, Dörfer K, Eckes J, Scharnagl H, Gierens H, Nissen H, Nauck MA, Wieland H, März W.

Hum Mutat. 2001 Aug;18(2):165-6.

PubMed [citation]
PMID:
11462246

The type of LDLR gene mutation predicts cardiovascular risk in children with familial hypercholesterolemia.

Guardamagna O, Restagno G, Rolfo E, Pederiva C, Martini S, Abello F, Baracco V, Pisciotta L, Pino E, Calandra S, Bertolini S.

J Pediatr. 2009 Aug;155(2):199-204.e2. doi: 10.1016/j.jpeds.2009.02.022. Epub 2009 May 15.

PubMed [citation]
PMID:
19446849
See all PubMed Citations (8)

Details of each submission

From Ambry Genetics, SCV002713634.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (8)

Description

The p.R574C variant (also known as c.1720C>T), located in coding exon 12 of the LDLR gene, results from a C to T substitution at nucleotide position 1720. The arginine at codon 574 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration has been detected in at least five individuals meeting clinical criteria for familial hypercholesterolemia (FH) as well as once in a cohort of individuals who experienced a myocardial infarction (MI) event before age 50 (Sharifi M et al. Metab. Clin. Exp., 2016 Mar;65:48-53; Thormaehlen AS et al. PLoS Genet., 2015 Feb;11:e1004855; Do R et al. Nature, 2015 Feb;518:102-6; Bertolini S et al. Atherosclerosis, 2013 Apr;227:342-8; Chmara M et al. J. Appl. Genet., 2010;51:95-106; Guardamagna O et al. J. Pediatr., 2009 Aug;155:199-204.e2; Nauck MS et al. Hum. Mutat., 2001 Aug;18:165-6). In addition, a different alteration located at the same position, p.R574S, has been detected in multiple individuals meeting clinical criteria for familial hypercholesterolemia (FH) (Paththinige CS et al. Lipids Health Dis, 2018 May;17:100; Du R et al. Springerplus, 2016 Dec;5:2095; Xiang R et al. Atherosclerosis, 2017 03;258:84-88); Ma Y et al. J Clin Lipidol Oct;12:230-235.e6). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 20, 2024