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NM_000527.5(LDLR):c.828C>A (p.Cys276Ter)

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Interpretation:
Conflicting interpretations of pathogenicity​

Benign(1);Likely benign(1);Pathogenic(4)

Review status:
criteria provided, conflicting interpretations
Submissions:
7 (Most recent: Jan 7, 2021)
Last evaluated:
Aug 24, 2020
Accession:
VCV000189298.5
Variation ID:
189298
Description:
single nucleotide variant
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NM_000527.5(LDLR):c.828C>A (p.Cys276Ter)

Allele ID
187195
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
19p13.2
Genomic location
19: 11107402 (GRCh38) GRCh38 UCSC
19: 11218078 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000019.10:g.11107402C>A
NC_000019.9:g.11218078C>A
NG_009060.1:g.23022C>A
... more HGVS
Protein change
C276*, C235*, C108*, C149*
Other names
-
Canonical SPDI
NC_000019.10:11107401:C:A
Functional consequence
-
Global minor allele frequency (GMAF)
0.00120 (T)

Allele frequency
-
Links
ClinGen: CA023773
LDLR-LOVD, British Heart Foundation: LDLR_000506
dbSNP: rs146651743
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 1 criteria provided, single submitter Aug 24, 2020 RCV001384763.1
Conflicting interpretations of pathogenicity 6 criteria provided, conflicting interpretations May 28, 2019 RCV000172961.6
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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
3093 3293

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely benign
(-)
criteria provided, single submitter
Method: research
Familial Hypercholesterolemia
(Autosomal dominant inheritance)
Allele origin: germline
Institute for Integrative and Experimental Genomics,University of Luebeck
Accession: SCV000212136.1
Submitted: (Mar 03, 2015)
Evidence details
Publications
PubMed (1)
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: SCV000295004.2
Submitted: (Apr 20, 2016)
Evidence details
Publications
PubMed (4)
Pathogenic
(Nov 05, 2016)
criteria provided, single submitter
Method: clinical testing
Familial hypercholesterolemia 1
(Autosomal dominant inheritance)
Allele origin: inherited
Molecular Genetics Laboratory,Centre for Cardiovascular Surgery and Transplantation
Additional submitter:
Centre of Molecular Biology and Gene Therapy,University Hospital Brno
Accession: SCV000540763.1
Submitted: (Mar 30, 2017)
Evidence details
Pathogenic
(Mar 01, 2016)
criteria provided, single submitter
Method: research
Familial hypercholesterolemia
(Autosomal dominant inheritance)
Allele origin: germline
Fundacion Hipercolesterolemia Familiar
Study: SAFEHEART
Accession: SCV000607507.1
Submitted: (Apr 20, 2017)
Evidence details
Benign
(May 28, 2019)
criteria provided, single submitter
Method: clinical testing
Familial hypercholesterolemia 1
Allele origin: unknown
Mendelics
Accession: SCV001140982.1
Submitted: (Oct 22, 2019)
Evidence details
Pathogenic
(Aug 24, 2020)
criteria provided, single submitter
Method: clinical testing
Familial hypercholesterolemia
Allele origin: germline
Invitae
Accession: SCV001584408.1
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (3)
Comment:
This sequence change creates a premature translational stop signal (p.Cys276*) in the LDLR gene. It is expected to result in an absent or disrupted protein … (more)
Pathogenic
(-)
no assertion criteria provided
Method: research
Familial hypercholesterolemia
Allele origin: germline
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum
Accession: SCV000606240.1
Submitted: (Apr 25, 2017)
Evidence details

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
Analysis of LDLR variants from homozygous FH patients carrying multiple mutations in the LDLR gene. Jiang L Atherosclerosis 2017 PMID: 28645073
Systematic analysis of variants related to familial hypercholesterolemia in families with premature myocardial infarction. Brænne I European journal of human genetics : EJHG 2016 PMID: 26036859
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
Molecular spectrum of autosomal dominant hypercholesterolemia in France. Marduel M Human mutation 2010 PMID: 20809525
Detection of mutations and large rearrangements of the low-density lipoprotein receptor gene in Taiwanese patients with familial hypercholesterolemia. Chiou KR The American journal of cardiology 2010 PMID: 20538126
Diagnosis of families with familial hypercholesterolaemia and/or Apo B-100 defect by means of DNA analysis of LDL-receptor gene mutations. Widhalm K Journal of inherited metabolic disease 2007 PMID: 17347910
Mutation analysis in 36 unrelated Spanish subjects with familial hypercholesterolemia: identification of 3 novel mutations in the LDL receptor gene. Mozas P Human mutation 2000 PMID: 10790219

Text-mined citations for rs146651743...

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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 Dec 04, 2021