NM_000527.5(LDLR):c.1054T>A (p.Cys352Ser) AND Cardiovascular phenotype

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: May 24, 2017
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:: RCV002411081.2

Allele description [Variation Report for NM_000527.5(LDLR):c.1054T>A (p.Cys352Ser)]

NM_000527.5(LDLR):c.1054T>A (p.Cys352Ser)

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.1054T>A (p.Cys352Ser)

HGVS:

NC_000019.10:g.11110765T>A
NG_009060.1:g.26385T>A
NM_000527.5:c.1054T>AMANE SELECT
NM_001195798.2:c.1054T>A
NM_001195799.2:c.931T>A
NM_001195800.2:c.550T>A
NM_001195803.2:c.673T>A
NP_000518.1:p.Cys352Ser
NP_000518.1:p.Cys352Ser
NP_001182727.1:p.Cys352Ser
NP_001182728.1:p.Cys311Ser
NP_001182729.1:p.Cys184Ser
NP_001182732.1:p.Cys225Ser
LRG_274t1:c.1054T>A
LRG_274:g.26385T>A
LRG_274p1:p.Cys352Ser
NC_000019.9:g.11221441T>A
NM_000527.4:c.1054T>A
c.1054T>A

Protein change:

C184S

Links:

LDLR-LOVD, British Heart Foundation: LDLR_001338; dbSNP: rs879254769

NCBI 1000 Genomes Browser:

rs879254769

Molecular consequence:

NM_000527.5:c.1054T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.1054T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.931T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.550T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.673T>A - 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
SCV002715425	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (May 24, 2017)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 21376320, 22353362, 26020417, 26875521 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002715425

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(May 24, 2017)

germline

clinical testing

PubMed (4)
[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

Array-based resequencing for mutations causing familial hypercholesterolemia.

Chiou KR, Charng MJ, Chang HM.

Atherosclerosis. 2011 Jun;216(2):383-9. doi: 10.1016/j.atherosclerosis.2011.02.006. Epub 2011 Mar 3.

PubMed [citation]

PMID:: 21376320

Common mutations of familial hypercholesterolemia patients in Taiwan: characteristics and implications of migrations from southeast China.

Chiou KR, Charng MJ.

Gene. 2012 Apr 25;498(1):100-6. doi: 10.1016/j.gene.2012.01.092. Epub 2012 Feb 14.

PubMed [citation]

PMID:: 22353362

See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV002715425.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

The p.C352S variant (also known as c.1054T>A), located in coding exon 7 of the LDLR gene, results from a T to A substitution at nucleotide position 1054. The cysteine at codon 352 is replaced by serine, an amino acid with dissimilar properties. This alteration has been detected in several familial hypercholesterolemia (FH) cohorts and segregates with disease in one small FH family (Chiou KR et al. Atherosclerosis. 2011;216:383-9; Saban-Ruiz J et al. Atherosclerosis. 2015;241:e115; Hu M et al. J. Atheroscler. Thromb. 2016;23:520-31; Medeiros AM et al. Genet. Med. 2016;18:316-24). A number of alterations in the same codon (p.C352Y, p.C352W, p.C352R, and p.C352F) have also been associated with FH (Hobbs HH et al. Hum. Mutat. 1992;1:445-66; Bertolini S et al. Arterioscler Thromb Vasc Biol. 1999;19(2)408-18; Widhalm K et al. J Inherit Metab Dis. 2007;30(2):239-47; Marduel M et al. Hum. Mutat. 2010;31(11):E1811-24). 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.

#	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: May 1, 2024

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