NM_000527.5(LDLR):c.1056C>G (p.Cys352Trp) AND Familial hypercholesterolemia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 26, 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:: RCV000586287.1

Allele description [Variation Report for NM_000527.5(LDLR):c.1056C>G (p.Cys352Trp)]

NM_000527.5(LDLR):c.1056C>G (p.Cys352Trp)

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.1056C>G (p.Cys352Trp)

Other names:

FH Avellino-1

HGVS:

NC_000019.10:g.11110767C>G
NG_009060.1:g.26387C>G
NM_000527.5:c.1056C>GMANE SELECT
NM_001195798.2:c.1056C>G
NM_001195799.2:c.933C>G
NM_001195800.2:c.552C>G
NM_001195803.2:c.675C>G
NP_000518.1:p.Cys352Trp
NP_000518.1:p.Cys352Trp
NP_001182727.1:p.Cys352Trp
NP_001182728.1:p.Cys311Trp
NP_001182729.1:p.Cys184Trp
NP_001182732.1:p.Cys225Trp
LRG_274t1:c.1056C>G
LRG_274:g.26387C>G
LRG_274p1:p.Cys352Trp
NC_000019.9:g.11221443C>G
NM_000527.4:c.1056C>G
c.1056C>G
p.(Cys352Trp)

Protein change:

C184W

Links:

LDLR-LOVD, British Heart Foundation: LDLR_001341; dbSNP: rs13306515

NCBI 1000 Genomes Browser:

rs13306515

Molecular consequence:

NM_000527.5:c.1056C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.1056C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.933C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.552C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.675C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Familial hypercholesterolemia
Identifiers:: MONDO: MONDO:0005439; MedGen: C0020445; OMIM: PS143890

Recent activity

Clear Turn Off Turn On

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
SCV000697183	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Jul 26, 2017)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 15823280, 23375686 LabCorp Variant Classification Summary - May 2015.docx Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000697183

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Jul 26, 2017)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

LabCorp Variant Classification Summary - May 2015.docx

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

Effect of low-density lipoprotein receptor mutation on lipoproteins and cardiovascular disease risk: a parent-offspring study.

Koeijvoets KC, Wiegman A, Rodenburg J, Defesche JC, Kastelein JJ, Sijbrands EJ.

Atherosclerosis. 2005 May;180(1):93-9. Epub 2004 Dec 19.

PubMed [citation]

PMID:: 15823280

Spectrum of mutations and phenotypic expression in patients with autosomal dominant hypercholesterolemia identified in Italy.

Bertolini S, Pisciotta L, Rabacchi C, Cefalù AB, Noto D, Fasano T, Signori A, Fresa R, Averna M, Calandra S.

Atherosclerosis. 2013 Apr;227(2):342-8. doi: 10.1016/j.atherosclerosis.2013.01.007. Epub 2013 Jan 19.

PubMed [citation]

PMID:: 23375686

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000697183.1

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

Description

Variant summary: The LDLR c.1056C>G (p.Cys352Trp) variant involves the alteration of a non-conserved nucleotide. 5/5 in silico tools predict a damaging outcome for this variant. The variant of interest has not been found in a large, broad control population, ExAC in 120928 control chromosomes. This variant was reported in multiple patients with familial hypercholesterolemia (FH), including a homozygous patient whose phenotype was more severe than the heterozygous patients (Bertolini_Atherosclerosis_2013, Fouchier_HG_2001), including . A functional study suggested that the variant causes a defective LDL receptor, though the data was not provided for independent assessment (Bertolini_Atherosclerosis_2013). In addition, one clinical diagnostic laboratory classified this variant as likely pathogenic. Taken together, this variant is classified as 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: Jan 13, 2025

ClinVar

Relating variation to medicine