NM_000527.5(LDLR):c.2230dup (p.Arg744fs) AND Familial hypercholesterolemia

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 9, 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:: RCV003582077.1

Allele description

NM_000527.5(LDLR):c.2230dup (p.Arg744fs)

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.2230dup (p.Arg744fs)

HGVS:

NC_000019.10:g.11123263dup
NG_009060.1:g.38883dup
NM_000527.5:c.2230dupMANE SELECT
NM_001195798.2:c.2230dup
NM_001195799.2:c.2107dup
NM_001195800.2:c.1726dup
NM_001195803.2:c.1696dup
NP_000518.1:p.Arg744Profs
NP_000518.1:p.Arg744fs
NP_001182727.1:p.Arg744fs
NP_001182728.1:p.Arg703fs
NP_001182729.1:p.Arg576fs
NP_001182732.1:p.Arg566fs
LRG_274t1:c.2230dup
LRG_274:g.38883dup
LRG_274p1:p.Arg744Profs
NC_000019.9:g.11233936_11233937insC
NC_000019.9:g.11233939dup
NM_000527.4:c.2230dup

Protein change:

R566fs

Molecular consequence:

NM_000527.5:c.2230dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195798.2:c.2230dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195799.2:c.2107dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195800.2:c.1726dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195803.2:c.1696dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004335498	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 9, 2023)	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

SCV004335498

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 9, 2023)

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 Invitae, SCV004335498.1

#	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.Arg744Profs*38) 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. 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 1, 2024

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