NM_000527.5(LDLR):c.518del (p.Cys173fs) AND Cardiovascular phenotype

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 23, 2018
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:: RCV002338787.2

Allele description [Variation Report for NM_000527.5(LDLR):c.518del (p.Cys173fs)]

NM_000527.5(LDLR):c.518del (p.Cys173fs)

Gene:

LDLR:low density lipoprotein receptor [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

19p13.2

Genomic location:

Preferred name:

NM_000527.5(LDLR):c.518del (p.Cys173fs)

HGVS:

NC_000019.10:g.11105424del
NG_009060.1:g.21044del
NM_000527.5:c.518delMANE SELECT
NM_001195798.2:c.518del
NM_001195799.2:c.395del
NM_001195800.2:c.314-1968del
NM_001195803.2:c.314-1141del
NP_000518.1:p.Cys173fs
NP_000518.1:p.Cys173fs
NP_001182727.1:p.Cys173fs
NP_001182728.1:p.Cys132fs
LRG_274t1:c.518del
LRG_274:g.21044del
LRG_274p1:p.Cys173fs
NC_000019.9:g.11216100del
NC_000019.9:g.11216100delG
NM_000527.4:c.518del
NM_000527.4:c.518delG
c.518delG
p.Cys173Serfs*33

Protein change:

C132fs

Links:

LDLR-LOVD, British Heart Foundation: LDLR_000073; dbSNP: rs879254559

NCBI 1000 Genomes Browser:

rs879254559

Molecular consequence:

NM_000527.5:c.518del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195798.2:c.518del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195799.2:c.395del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195800.2:c.314-1968del - intron variant - [Sequence Ontology: SO:0001627]
NM_001195803.2:c.314-1141del - intron variant - [Sequence Ontology: SO:0001627]

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
SCV002644165	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Feb 23, 2018)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 22390909, 8828982 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002644165

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Feb 23, 2018)

germline

clinical testing

PubMed (2)
[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 in relation to functionality of sequence variants in the gene coding for the low-density lipoprotein receptor: a study among 29,365 individuals tested for 64 specific low-density lipoprotein-receptor sequence variants.

Huijgen R, Kindt I, Defesche JC, Kastelein JJ.

Eur Heart J. 2012 Sep;33(18):2325-30. doi: 10.1093/eurheartj/ehs038. Epub 2012 Mar 4.

PubMed [citation]

PMID:: 22390909

Two novel mutations in the LDL receptor gene: common causes of familial hypercholesterolemia in a Spanish population.

Cenarro A, Jensen HK, Civeira F, Casao E, Ferrando J, González-Bonillo J, Pocoví M, Gregersen N.

Clin Genet. 1996 Apr;49(4):180-5.

PubMed [citation]

PMID:: 8828982

Details of each submission

From Ambry Genetics, SCV002644165.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The c.518delG pathogenic mutation, located in coding exon 4 of the LDLR gene, results from a deletion of one nucleotide at nucleotide position 518, causing a translational frameshift with a predicted alternate stop codon (p.C173Sfs*33). This alteration has been reported in individuals with hypercholesterolemia (Cenarro A et al. Clin. Genet., 1996 Apr;49:180-5; Huijgen R et al. Eur. Heart J., 2012 Sep;33:2325-30). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, 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: Jun 23, 2024

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