NM_000527.5(LDLR):c.828C>A (p.Cys276Ter) AND Familial hypercholesterolemia 1

Clinical significance:Conflicting interpretations of pathogenicity, Benign(1);Likely benign(1);Pathogenic(3) (Last evaluated: May 28, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
6 submissions [Details]
Record status:
current
Accession:
RCV000172961.6

Allele description [Variation Report for NM_000527.5(LDLR):c.828C>A (p.Cys276Ter)]

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

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.828C>A (p.Cys276Ter)
HGVS:
  • NC_000019.10:g.11107402C>A
  • NG_009060.1:g.23022C>A
  • NM_000527.4:c.828C>A
  • NM_000527.5:c.828C>AMANE SELECT
  • NM_001195798.2:c.828C>A
  • NM_001195799.2:c.705C>A
  • NM_001195800.2:c.324C>A
  • NM_001195803.2:c.447C>A
  • NP_000518.1:p.Cys276Ter
  • NP_000518.1:p.Cys276Ter
  • NP_001182727.1:p.Cys276Ter
  • NP_001182728.1:p.Cys235Ter
  • NP_001182729.1:p.Cys108Ter
  • NP_001182732.1:p.Cys149Ter
  • LRG_274t1:c.828C>A
  • LRG_274:g.23022C>A
  • LRG_274p1:p.Cys276Ter
  • NC_000019.9:g.11218078C>A
  • c.828C>A
Protein change:
C108*
Links:
LDLR-LOVD, British Heart Foundation: LDLR_000506; dbSNP: rs146651743
NCBI 1000 Genomes Browser:
rs146651743
Molecular consequence:
  • NM_000527.4:c.828C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_000527.5:c.828C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001195798.2:c.828C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001195799.2:c.705C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001195800.2:c.324C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001195803.2:c.447C>A - nonsense - [Sequence Ontology: SO:0001587]
Observations:
9

Condition(s)

Name:
Familial hypercholesterolemia 1 (FHCL1)
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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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000212136Institute for Integrative and Experimental Genomics,University of Luebeckcriteria provided, single submitter
Likely benigngermlineresearch

PubMed (1)
[See all records that cite this PMID]

SCV000295004LDLR-LOVD, British Heart Foundationcriteria provided, single submitter
Pathogenic
(Mar 25, 2016)
germlineliterature only

PubMed (4)
[See all records that cite these PMIDs]

Citation Link,

SCV000540763Molecular Genetics Laboratory,Centre for Cardiovascular Surgery and Transplantation

See additional submitters

criteria provided, single submitter
Pathogenic
(Nov 5, 2016)
inheritedclinical testing

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

SCV000606240Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrumno assertion criteria providedPathogenicgermlineresearch

SCV000607507Fundacion Hipercolesterolemia Familiar - SAFEHEARTcriteria provided, single submitter
Pathogenic
(Mar 1, 2016)
germlineresearch

PubMed (1)
[See all records that cite this PMID]

SCV001140982Mendelicscriteria provided, single submitter
Benign
(May 28, 2019)
unknownclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes4not providednot provided4not providedliterature only
not providedgermlinenonot provided1not providednot providednot providedresearch
not providedgermlineunknownnot providednot providednot providednot providednot providedresearch
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing
Caucasianinheritedyes119not provided3964yesclinical testing

Citations

PubMed

Systematic analysis of variants related to familial hypercholesterolemia in families with premature myocardial infarction.

Brænne I, Kleinecke M, Reiz B, Graf E, Strom T, Wieland T, Fischer M, Kessler T, Hengstenberg C, Meitinger T, Erdmann J, Schunkert H.

Eur J Hum Genet. 2016 Feb;24(2):191-7. doi: 10.1038/ejhg.2015.100. Epub 2015 Jun 3.

PubMed [citation]
PMID:
26036859
PMCID:
PMC4717192

Mutation analysis in 36 unrelated Spanish subjects with familial hypercholesterolemia: identification of 3 novel mutations in the LDL receptor gene.

Mozas P, Cenarro A, Civeira F, Castillo S, Ros E, Pocovi M.

Hum Mutat. 2000 May;15(5):483-4.

PubMed [citation]
PMID:
10790219
See all PubMed Citations (7)

Details of each submission

From Institute for Integrative and Experimental Genomics,University of Luebeck, SCV000212136.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedresearch PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenonot providednot providednot providednot providednot provided1not provided

From LDLR-LOVD, British Heart Foundation, SCV000295004.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedliterature only PubMed (4)
2not provided1not providednot providedliterature only PubMed (4)
3not provided1not providednot providedliterature only PubMed (4)
4not provided1not providednot providedliterature only PubMed (4)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyes1not providednot provided1not providednot providednot provided
2germlineyes1not providednot provided1not providednot providednot provided
3germlineyes1not providednot provided1not providednot providednot provided
4germlineyes1not providednot provided1not providednot providednot provided

From Molecular Genetics Laboratory,Centre for Cardiovascular Surgery and Transplantation, SCV000540763.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1Caucasian11not providedyesclinical testing PubMed (2)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1inheritedyes3964Whole bloodnot provided11not provided9not provided

From Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum, SCV000606240.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedresearchnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Fundacion Hipercolesterolemia Familiar - SAFEHEART, SCV000607507.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedresearch PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Mendelics, SCV001140982.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 8, 2021

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