NM_000527.5(LDLR):c.908_926dup (p.Pro309_Ile310insGlyLeuValArgTer) AND Familial hypercholesterolemia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 2, 2022
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:: RCV002515609.3

Allele description [Variation Report for NM_000527.5(LDLR):c.908_926dup (p.Pro309_Ile310insGlyLeuValArgTer)]

NM_000527.5(LDLR):c.908_926dup (p.Pro309_Ile310insGlyLeuValArgTer)

Gene:

LDLR:low density lipoprotein receptor [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

19p13.2

Genomic location:

Preferred name:

NM_000527.5(LDLR):c.908_926dup (p.Pro309_Ile310insGlyLeuValArgTer)

HGVS:

NC_000019.10:g.11107482_11107500dup
NG_009060.1:g.23102_23120dup
NM_000527.5:c.908_926dupMANE SELECT
NM_001195798.2:c.908_926dup
NM_001195799.2:c.785_803dup
NM_001195800.2:c.404_422dup
NM_001195803.2:c.527_545dup
NP_000518.1:p.Ile310_Lys311insGlyLeuValArgTer
NP_000518.1:p.Pro309_Ile310insGlyLeuValArgTer
NP_001182727.1:p.Pro309_Ile310insGlyLeuValArgTer
NP_001182728.1:p.Pro268_Ile269insGlyLeuValArgTer
NP_001182729.1:p.Pro141_Ile142insGlyLeuValArgTer
NP_001182732.1:p.Pro182_Ile183insGlyLeuValArgTer
LRG_274t1:c.908_926dup
LRG_274:g.23102_23120dup
LRG_274p1:p.Ile310_Lys311insGlyLeuValArgTer
NC_000019.9:g.11218155_11218156insCCGGGACTGGTCAGATGAA
NC_000019.9:g.11218158_11218176dup
NM_000527.4:c.908_926dup

Links:

dbSNP: rs875989908

NCBI 1000 Genomes Browser:

rs875989908

Molecular consequence:

NM_000527.5:c.908_926dup - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_001195798.2:c.908_926dup - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_001195799.2:c.785_803dup - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_001195800.2:c.404_422dup - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_001195803.2:c.527_545dup - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_000527.5:c.908_926dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001195798.2:c.908_926dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001195799.2:c.785_803dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001195800.2:c.404_422dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001195803.2:c.527_545dup - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

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

Recent activity

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DC034479 Osada Taira anterior endomesoderm (AEM) pCS105 cDNA library Xenopus lae...
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gi|118938006|gnl|dbEST|43246679|dbj 4479.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003226573	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 2, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 20809525, 28645073, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003226573

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 2, 2022)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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, SCV003226573.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Ile310Glyfs*5) 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). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with LDLR-related conditions. ClinVar contains an entry for this variant (Variation ID: 226335). For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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