NM_000527.5(LDLR):c.353del (p.Asp118fs) AND Familial hypercholesterolemia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 27, 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:: RCV003581595.2

Allele description [Variation Report for NM_000527.5(LDLR):c.353del (p.Asp118fs)]

NM_000527.5(LDLR):c.353del (p.Asp118fs)

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.353del (p.Asp118fs)

HGVS:

NC_000019.10:g.11105259del
NG_009060.1:g.20879del
NM_000527.5:c.353delMANE SELECT
NM_001195798.2:c.353del
NM_001195799.2:c.230del
NM_001195800.2:c.314-2133del
NM_001195803.2:c.314-1306del
NP_000518.1:p.Asp118fs
NP_001182727.1:p.Asp118fs
NP_001182728.1:p.Asp77fs
LRG_274:g.20879del
NC_000019.9:g.11215935del
NC_000019.9:g.11215935delA
NM_000527.4:c.353delA
c.353delA
p.Asp118Valfs*88

Protein change:

D118fs

Links:

LDLR-LOVD, British Heart Foundation: LDLR_000384; dbSNP: rs879254488

NCBI 1000 Genomes Browser:

rs879254488

Molecular consequence:

NM_000527.5:c.353del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195798.2:c.353del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195799.2:c.230del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195800.2:c.314-2133del - intron variant - [Sequence Ontology: SO:0001627]
NM_001195803.2:c.314-1306del - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

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

Recent activity

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Homo sapiens FA core complex associated protein 20 (FAAP20), transcript variant ...
Homo sapiens FA core complex associated protein 20 (FAAP20), transcript variant 3, mRNA
gi|1844084054|ref|NM_001256945.2|

Nucleotide
Homo sapiens chromosome 1 open reading frame 86, mRNA (cDNA clone MGC:120153 IMA...
Homo sapiens chromosome 1 open reading frame 86, mRNA (cDNA clone MGC:120153 IMAGE:40022365), complete cds
gi|115527148|gb|BC103992.2|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004298313	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 27, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 10208479, 20809525, 28645073, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004298313

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 27, 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

The type of mutation in the low density lipoprotein receptor gene influences the cholesterol-lowering response of the HMG-CoA reductase inhibitor simvastatin in patients with heterozygous familial hypercholesterolaemia.

Heath KE, Gudnason V, Humphries SE, Seed M.

Atherosclerosis. 1999 Mar;143(1):41-54.

PubMed [citation]

PMID:: 10208479

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, SCV004298313.1

#	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. ClinVar contains an entry for this variant (Variation ID: 251169). This premature translational stop signal has been observed in individual(s) with familial hypercholesterolemia (PMID: 10208479). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asp118Valfs*88) 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).

#	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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