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

Clinical significance:Pathogenic (Last evaluated: Aug 24, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001384763.1

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]

Condition(s)

Name:
Familial hypercholesterolemia (FH)
Identifiers:
MONDO: MONDO:0005439; MedGen: C0020445; OMIM: PS143890

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001584408Invitaecriteria provided, single submitter
Pathogenic
(Aug 24, 2020)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

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

Molecular spectrum of autosomal dominant hypercholesterolemia in France.

Marduel M, Carrié A, Sassolas A, Devillers M, Carreau V, Di Filippo M, Erlich D, Abifadel M, Marques-Pinheiro A, Munnich A, Junien C; French ADH Research Network., Boileau C, Varret M, Rabès JP.

Hum Mutat. 2010 Nov;31(11):E1811-24. doi: 10.1002/humu.21348.

PubMed [citation]
PMID:
20809525
PMCID:
PMC3152176
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001584408.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

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 product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with autosomal dominant familial hypercholesterolemia (PMID: 10790219). ClinVar contains an entry for this variant (Variation ID: 189298). Loss-of-function variants in LDLR are known to be pathogenic (PMID: 20809525, 28645073). For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 7, 2021

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