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

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 25, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV001384763.4

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)
Other names:
NM_000527.5(LDLR):c.828C>A
HGVS:
  • NC_000019.10:g.11107402C>A
  • NG_009060.1:g.23022C>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
  • NM_000527.4:c.828C>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_000527.5: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

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001584408Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Apr 25, 2023) 		germlineclinical testing

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

Help

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, SCV001584408.4

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

Description

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

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

Last Updated: Feb 20, 2024