NM_000527.5(LDLR):c.906C>G (p.Cys302Trp) AND Hypercholesterolemia, familial, 1

Germline classification:: Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:: Oct 16, 2023
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:: RCV000237924.4

Allele description [Variation Report for NM_000527.5(LDLR):c.906C>G (p.Cys302Trp)]

NM_000527.5(LDLR):c.906C>G (p.Cys302Trp)

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.906C>G (p.Cys302Trp)

Other names:

NP_000518.1:p.C302W

HGVS:

NC_000019.10:g.11107480C>G
NG_009060.1:g.23100C>G
NM_000527.5:c.906C>GMANE SELECT
NM_001195798.2:c.906C>G
NM_001195799.2:c.783C>G
NM_001195800.2:c.402C>G
NM_001195803.2:c.525C>G
NP_000518.1:p.Cys302Trp
NP_000518.1:p.Cys302Trp
NP_001182727.1:p.Cys302Trp
NP_001182728.1:p.Cys261Trp
NP_001182729.1:p.Cys134Trp
NP_001182732.1:p.Cys175Trp
LRG_274t1:c.906C>G
LRG_274:g.23100C>G
LRG_274p1:p.Cys302Trp
NC_000019.9:g.11218156C>G
NM_000527.4:c.906C>G
P01130:p.Cys302Trp
c.906C>G

Protein change:

C134W

Links:

LDLR-LOVD, British Heart Foundation: LDLR_000409; UniProtKB: P01130#VAR_005354; dbSNP: rs879254716

NCBI 1000 Genomes Browser:

rs879254716

Molecular consequence:

NM_000527.5:c.906C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.906C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.783C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.402C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.525C>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
SCV000295043	LDLR-LOVD, British Heart Foundation	criteria provided, single submitter (ACGS Guidelines, 2013)	Likely pathogenic (Mar 25, 2016)	germline	literature only	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV000484691	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]
SCV001467724	Rajaie Cardiovascular, Medical and Research Center, Iran University of Medical Sciences	no assertion criteria provided	Pathogenic	somatic	research
SCV004100718	Institute of Human Genetics, University of Leipzig Medical Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 16, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	somatic	yes	1	not provided	not provided	not provided	not provided	research
not provided	germline	yes	2	not provided	not provided	1	not provided	clinical testing, literature only
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Characterization of mutations in the low density lipoprotein (LDL)-receptor gene in patients with homozygous familial hypercholesterolemia, and frequency of these mutations in FH patients in the United Kingdom.

Webb JC, Sun XM, McCarthy SN, Neuwirth C, Thompson GR, Knight BL, Soutar AK.

J Lipid Res. 1996 Feb;37(2):368-81.

PubMed [citation]

PMID:: 9026534

Polygenic Versus Monogenic Causes of Hypercholesterolemia Ascertained Clinically.

Wang J, Dron JS, Ban MR, Robinson JF, McIntyre AD, Alazzam M, Zhao PJ, Dilliott AA, Cao H, Huff MW, Rhainds D, Low-Kam C, Dubé MP, Lettre G, Tardif JC, Hegele RA.

Arterioscler Thromb Vasc Biol. 2016 Dec;36(12):2439-2445. Epub 2016 Oct 20.

PubMed [citation]

PMID:: 27765764

See all PubMed Citations (3)

Details of each submission

From LDLR-LOVD, British Heart Foundation, SCV000295043.2

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

#	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

From Robarts Research Institute, Western University, SCV000484691.1

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

From Rajaie Cardiovascular, Medical and Research Center, Iran University of Medical Sciences, SCV001467724.1

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

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

From Institute of Human Genetics, University of Leipzig Medical Center, SCV004100718.1

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

Description

Criteria applied: PM5_STR,PS4_MOD,PM1,PM2_SUP,PP3

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

Last Updated: Nov 4, 2023

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