NM_000527.5(LDLR):c.519C>G (p.Cys173Trp) AND Hypercholesterolemia, familial, 1

Germline classification:: Pathogenic/Likely pathogenic (5 submissions)
Last evaluated:: May 11, 2019
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000238354.11

Allele description [Variation Report for NM_000527.5(LDLR):c.519C>G (p.Cys173Trp)]

NM_000527.5(LDLR):c.519C>G (p.Cys173Trp)

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.519C>G (p.Cys173Trp)

Other names:

NP_000518.1:p.C173W

HGVS:

NC_000019.10:g.11105425C>G
NG_009060.1:g.21045C>G
NM_000527.5:c.519C>GMANE SELECT
NM_001195798.2:c.519C>G
NM_001195799.2:c.396C>G
NM_001195800.2:c.314-1967C>G
NM_001195803.2:c.314-1140C>G
NP_000518.1:p.Cys173Trp
NP_000518.1:p.Cys173Trp
NP_001182727.1:p.Cys173Trp
NP_001182728.1:p.Cys132Trp
LRG_274t1:c.519C>G
LRG_274:g.21045C>G
LRG_274p1:p.Cys173Trp
NC_000019.9:g.11216101C>G
NM_000527.4:c.519C>G
P01130:p.Cys173Trp
c.519C>G

Protein change:

C132W

Links:

LDLR-LOVD, British Heart Foundation: LDLR_000391; UniProtKB: P01130#VAR_005325; dbSNP: rs769318035

NCBI 1000 Genomes Browser:

rs769318035

Molecular consequence:

NM_001195800.2:c.314-1967C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001195803.2:c.314-1140C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000527.5:c.519C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.519C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.396C>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Hypercholesterolemia, familial, 1
Synonyms:: LDL RECEPTOR DISORDER; Hyperlipoproteinemia Type IIa; HYPER-LOW-DENSITY-LIPOPROTEINEMIA; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007750; MedGen: C0745103; Orphanet: 391665; OMIM: 143890

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000294767	LDLR-LOVD, British Heart Foundation	criteria provided, single submitter (ACGS Guidelines, 2013)	Likely pathogenic (Mar 25, 2016)	germline	literature only	PubMed (4) [See all records that cite these PMIDs] 10090484, 11810272, 9452094, 26343872 Citation Link,
SCV000484679	Robarts Research Institute, Western University	criteria provided, single submitter (Wang et al. (Arterioscler Thromb Vasc Biol. 2016))	Likely pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000583691	U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 30, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000606146	Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum	no assertion criteria provided	Pathogenic	germline	research
SCV001432610	Brunham Lab, Centre for Heart and Lung Innovation, University of British Columbia	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 11, 2019)	germline	research	PubMed (2) [See all records that cite these PMIDs] 25741868, 31345425

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	13	1	not provided	8	not provided	clinical testing, literature only, research
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	research

Citations

PubMed

Mutation analysis in 46 German families with familial hypercholesterolemia: identification of 8 new mutations. Mutations in brief no. 226. Online.

Ebhardt M, Schmidt H, Doerk T, Tietge U, Haas R, Manns MP, Schmidtke J, Stuhrmann M.

Hum Mutat. 1999;13(3):257.

PubMed [citation]

PMID:: 10090484

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 (7)

Details of each submission

From LDLR-LOVD, British Heart Foundation, SCV000294767.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	literature only	PubMed (4)
2	not provided	1	not provided	not provided	literature only	PubMed (4)
3	not provided	1	not provided	not provided	literature only	PubMed (4)
4	not provided	1	not provided	not provided	literature only	PubMed (4)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided
2	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided
3	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided
4	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided

From Robarts Research Institute, Western University, SCV000484679.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		2	not provided	not provided	not provided

From U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille, SCV000583691.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	not provided	not provided	clinical testing	PubMed (1)

Description

Dutch Lipid Clinic Scoring : Definite FH

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		3	not provided	1	not provided

From Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum, SCV000606146.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	not provided

#	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

From Brunham Lab, Centre for Heart and Lung Innovation, University of British Columbia, SCV001432610.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	research	PubMed (2)
2	not provided	1	not provided	not provided	research	PubMed (2)
3	not provided	1	not provided	not provided	research	PubMed (2)
4	not provided	1	not provided	not provided	research	PubMed (2)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided
2	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided
3	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided
4	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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