U.S. flag

An official website of the United States government

NM_000527.5(LDLR):c.1222G>T (p.Glu408Ter) AND Familial hypercholesterolemia

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 14, 2021
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:
RCV001864673.4

Allele description [Variation Report for NM_000527.5(LDLR):c.1222G>T (p.Glu408Ter)]

NM_000527.5(LDLR):c.1222G>T (p.Glu408Ter)

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.1222G>T (p.Glu408Ter)
HGVS:
  • NC_000019.10:g.11113313G>T
  • NG_009060.1:g.28933G>T
  • NM_000527.5:c.1222G>TMANE SELECT
  • NM_001195798.2:c.1222G>T
  • NM_001195799.2:c.1099G>T
  • NM_001195800.2:c.718G>T
  • NM_001195803.2:c.841G>T
  • NP_000518.1:p.Glu408Ter
  • NP_001182727.1:p.Glu408Ter
  • NP_001182728.1:p.Glu367Ter
  • NP_001182729.1:p.Glu240Ter
  • NP_001182732.1:p.Glu281Ter
  • LRG_274:g.28933G>T
  • NC_000019.9:g.11223989G>T
Protein change:
E240*
Links:
dbSNP: rs137943601
NCBI 1000 Genomes Browser:
rs137943601
Molecular consequence:
  • NM_000527.5:c.1222G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001195798.2:c.1222G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001195799.2:c.1099G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001195800.2:c.718G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001195803.2:c.841G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002140297Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Dec 14, 2021) 		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 detection in patients with familial hypercholesterolaemia using heteroduplex and single strand conformation polymorphism analysis by capillary electrophoresis.

Sozen M, Whittall R, Humphries SE.

Atheroscler Suppl. 2004 Dec;5(5):7-11.

PubMed [citation]
PMID:
15556093

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV002140297.3

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant is also known as p.E387X. This premature translational stop signal has been observed in individual(s) with familial hypercholesterolemia (PMID: 15556093). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu408*) 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: Sep 29, 2024