NM_000527.5(LDLR):c.670_672del (p.Asp224del) AND Familial hypercholesterolemia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 12, 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:: RCV003043619.3

Allele description [Variation Report for NM_000527.5(LDLR):c.670_672del (p.Asp224del)]

NM_000527.5(LDLR):c.670_672del (p.Asp224del)

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.670_672del (p.Asp224del)

HGVS:

NC_000019.10:g.11105576_11105578del
NG_009060.1:g.21196_21198del
NM_000527.5:c.670_672delMANE SELECT
NM_001195798.2:c.670_672del
NM_001195799.2:c.547_549del
NM_001195800.2:c.314-1816_314-1814del
NM_001195803.2:c.314-989_314-987del
NP_000518.1:p.Asp224del
NP_000518.1:p.Asp224del
NP_001182727.1:p.Asp224del
NP_001182728.1:p.Asp183del
LRG_274t1:c.670_672del
LRG_274:g.21196_21198del
LRG_274p1:p.Asp224del
NC_000019.9:g.11216252_11216254del
NM_000527.4:c.670_672delGAC

Protein change:

D183del

Molecular consequence:

NM_000527.5:c.670_672del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001195798.2:c.670_672del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001195799.2:c.547_549del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001195800.2:c.314-1816_314-1814del - intron variant - [Sequence Ontology: SO:0001627]
NM_001195803.2:c.314-989_314-987del - intron variant - [Sequence Ontology: SO:0001627]

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
SCV003345314	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 12, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 15576851, 19843101, 30876530, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003345314

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 12, 2022)

germline

clinical testing

PubMed (4)
[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

Multiplex ligation-dependent probe amplification of LDLR enhances molecular diagnosis of familial hypercholesterolemia.

Wang J, Ban MR, Hegele RA.

J Lipid Res. 2005 Feb;46(2):366-72. Epub 2004 Dec 1.

PubMed [citation]

PMID:: 15576851

Mutation screening in patients for familial hypercholesterolaemia (ADH).

Taylor A, Patel K, Tsedeke J, Humphries SE, Norbury G.

Clin Genet. 2010 Jan;77(1):97-9. doi: 10.1111/j.1399-0004.2009.01279.x. Epub 2009 Oct 14. No abstract available.

PubMed [citation]

PMID:: 19843101

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003345314.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the LDLR protein in which other variant(s) (p.Asp224Asn) have been determined to be pathogenic (PMID: 15576851, 19843101, 30876530; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant has not been reported in the literature in individuals affected with LDLR-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant, c.670_672del, results in the deletion of 1 amino acid(s) of the LDLR protein (p.Asp224del), but otherwise preserves the integrity of the reading frame.

#	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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