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NM_000527.5(LDLR):c.378del (p.Phe126fs) AND Familial hypercholesterolemia

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jul 28, 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:
RCV001235875.5

Allele description [Variation Report for NM_000527.5(LDLR):c.378del (p.Phe126fs)]

NM_000527.5(LDLR):c.378del (p.Phe126fs)

Gene:
LDLR:low density lipoprotein receptor [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
19p13.2
Genomic location:
Preferred name:
NM_000527.5(LDLR):c.378del (p.Phe126fs)
HGVS:
  • NC_000019.10:g.11105284del
  • NG_009060.1:g.20904del
  • NM_000527.5:c.378delMANE SELECT
  • NM_001195798.2:c.378del
  • NM_001195799.2:c.255del
  • NM_001195800.2:c.314-2108del
  • NM_001195803.2:c.314-1281del
  • NP_000518.1:p.Phe126fs
  • NP_000518.1:p.Phe126fs
  • NP_001182727.1:p.Phe126fs
  • NP_001182728.1:p.Phe85fs
  • LRG_274t1:c.378del
  • LRG_274:g.20904del
  • LRG_274p1:p.Phe126fs
  • NC_000019.9:g.11215960del
  • NM_000527.4:c.378del
  • NM_000527.4:c.378delC
Protein change:
F126fs
Links:
dbSNP: rs1555803213
NCBI 1000 Genomes Browser:
rs1555803213
Molecular consequence:
  • NM_000527.5:c.378del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001195798.2:c.378del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001195799.2:c.255del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001195800.2:c.314-2108del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001195803.2:c.314-1281del - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:
Familial hypercholesterolemia
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
SCV001408581Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jul 28, 2021) 		germlineclinical testing

PubMed (3)
[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

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

Analysis of LDLR variants from homozygous FH patients carrying multiple mutations in the LDLR gene.

Jiang L, Benito-Vicente A, Tang L, Etxebarria A, Cui W, Uribe KB, Pan XD, Ostolaza H, Yang SW, Zhou YJ, Martin C, Wang LY.

Atherosclerosis. 2017 Aug;263:163-170. doi: 10.1016/j.atherosclerosis.2017.06.014. Epub 2017 Jun 8.

PubMed [citation]
PMID:
28645073
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001408581.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in LDLR are known to be pathogenic (PMID: 20809525, 28645073). This variant has not been reported in the literature in individuals with LDLR-related conditions. ClinVar contains an entry for this variant (Variation ID: 440565). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Phe126Leufs*80) in the LDLR gene. It is expected to result in an absent or disrupted protein product.

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

Last Updated: Sep 29, 2024