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NM_000527.5(LDLR):c.427T>C (p.Cys143Arg)

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
6 (Most recent: Jan 7, 2021)
Last evaluated:
Mar 22, 2020
Accession:
VCV000251219.4
Variation ID:
251219
Description:
single nucleotide variant
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NM_000527.5(LDLR):c.427T>C (p.Cys143Arg)

Allele ID
245557
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
19p13.2
Genomic location
19: 11105333 (GRCh38) GRCh38 UCSC
19: 11216009 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000019.9:g.11216009T>C
NC_000019.10:g.11105333T>C
NM_000527.5:c.427T>C MANE Select NP_000518.1:p.Cys143Arg missense
... more HGVS
Protein change
C143R, C102R
Other names
-
Canonical SPDI
NC_000019.10:11105332:T:C
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA10584916
LDLR-LOVD, British Heart Foundation: LDLR_000058
UniProtKB: P01130#VAR_072828
dbSNP: rs875989901
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic/Likely pathogenic 4 criteria provided, multiple submitters, no conflicts Oct 31, 2018 RCV000237201.3
Pathogenic/Likely pathogenic 2 criteria provided, multiple submitters, no conflicts Mar 22, 2020 RCV000775039.3
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
LDLR Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
3087 3287

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(Mar 25, 2016)
criteria provided, single submitter
Method: literature only
Familial hypercholesterolemia
(Autosomal dominant inheritance)
Allele origin: germline
LDLR-LOVD, British Heart Foundation
Accession: SCV000294704.2
Submitted: (Apr 20, 2016)
Evidence details
Publications
PubMed (3)
Likely pathogenic
(Mar 01, 2016)
criteria provided, single submitter
Method: research
Familial hypercholesterolemia
(Autosomal dominant inheritance)
Allele origin: germline
Cardiovascular Research Group,Instituto Nacional de Saude Doutor Ricardo Jorge
Accession: SCV000322898.1
Submitted: (Oct 14, 2016)
Evidence details
Comment:
0/190 non-FH alleles
Likely pathogenic
(Nov 05, 2016)
criteria provided, single submitter
Method: clinical testing
Familial hypercholesterolemia 1
(Autosomal dominant inheritance)
Allele origin: unknown
Molecular Genetics Laboratory,Centre for Cardiovascular Surgery and Transplantation
Additional submitter:
Centre of Molecular Biology and Gene Therapy,University Hospital Brno
Accession: SCV000540715.1
Submitted: (Mar 30, 2017)
Evidence details
Comment:
Disrupt disulfide bridge between Cys128 and Cys143.
Pathogenic
(Oct 31, 2018)
criteria provided, single submitter
Method: clinical testing
Familial hypercholesterolemia 1
Allele origin: unknown
Fulgent Genetics,Fulgent Genetics
Accession: SCV000894166.1
Submitted: (Nov 14, 2018)
Evidence details
Publications
PubMed (1)
DOI: 10.1038/gim.2015.30
Likely pathogenic
(Mar 12, 2019)
criteria provided, single submitter
Method: clinical testing
Familial hypercholesterolemia
Allele origin: germline
Color Health, Inc
Accession: SCV000909136.2
Submitted: (May 19, 2020)
Comment:
This missense variant (also known as p.Cys122Arg in the mature protein) is located in the third LDLR type A repeat of the ligand binding domain … (more)
Evidence details
Pathogenic
(Mar 22, 2020)
criteria provided, single submitter
Method: clinical testing
Familial hypercholesterolemia
Allele origin: germline
Invitae
Accession: SCV001580452.1
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (7)
Comment:
This sequence change replaces cysteine with arginine at codon 143 of the LDLR protein (p.Cys143Arg). The cysteine residue is highly conserved and there is a … (more)

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Richards S Genetics in medicine : official journal of the American College of Medical Genetics 2015 PMID: 25741868
The molecular basis of familial hypercholesterolemia in the Czech Republic: spectrum of LDLR mutations and genotype-phenotype correlations. Tichý L Atherosclerosis 2012 PMID: 22698793
An APEX-based genotyping microarray for the screening of 168 mutations associated with familial hypercholesterolemia. Dušková L Atherosclerosis 2011 PMID: 21310417
Update of the Portuguese Familial Hypercholesterolaemia Study. Medeiros AM Atherosclerosis 2010 PMID: 20828696
Update and analysis of the University College London low density lipoprotein receptor familial hypercholesterolemia database. Leigh SE Annals of human genetics 2008 PMID: 18325082
Identification of recurrent and novel mutations in the LDL receptor gene in German patients with familial hypercholesterolemia. Nauck MS Human mutation 2001 PMID: 11462246
Three-dimensional structure of a cysteine-rich repeat from the low-density lipoprotein receptor. Daly NL Proceedings of the National Academy of Sciences of the United States of America 1995 PMID: 7603991
Disulfide bridges of a cysteine-rich repeat of the LDL receptor ligand-binding domain. Bieri S Biochemistry 1995 PMID: 7548065
Structures and functions of multiligand lipoprotein receptors: macrophage scavenger receptors and LDL receptor-related protein (LRP). Krieger M Annual review of biochemistry 1994 PMID: 7979249

Text-mined citations for rs875989901...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated May 13, 2021