NM_000527.5(LDLR):c.1878del (p.Ala627fs) AND Familial hypercholesterolemia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 28, 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:: RCV001861359.5

Allele description [Variation Report for NM_000527.5(LDLR):c.1878del (p.Ala627fs)]

NM_000527.5(LDLR):c.1878del (p.Ala627fs)

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.1878del (p.Ala627fs)

HGVS:

NC_000019.10:g.11120124del
NG_009060.1:g.35744del
NM_000527.5:c.1878delMANE SELECT
NM_001195798.2:c.1878del
NM_001195799.2:c.1755del
NM_001195800.2:c.1374del
NM_001195803.2:c.1497del
NP_000518.1:p.Ala627fs
NP_000518.1:p.E626Efs*38
NP_001182727.1:p.Ala627fs
NP_001182728.1:p.Ala586fs
NP_001182729.1:p.Ala459fs
NP_001182732.1:p.Ala500fs
LRG_274:g.35744del
NC_000019.9:g.11230799del
NC_000019.9:g.11230800del
NM_000527.4:c.1878delA

Protein change:

A459fs

Links:

dbSNP: rs1057516134

NCBI 1000 Genomes Browser:

rs1057516134

Molecular consequence:

NM_000527.5:c.1878del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195798.2:c.1878del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195799.2:c.1755del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195800.2:c.1374del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195803.2:c.1497del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002232528	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 28, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 19026292, 20809525, 28645073, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002232528

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 28, 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

Longitudinal evaluation and assessment of cardiovascular disease in patients with homozygous familial hypercholesterolemia.

Kolansky DM, Cuchel M, Clark BJ, Paridon S, McCrindle BW, Wiegers SE, Araujo L, Vohra Y, Defesche JC, Wilson JM, Rader DJ.

Am J Cardiol. 2008 Dec 1;102(11):1438-43. doi: 10.1016/j.amjcard.2008.07.035. Epub 2008 Sep 11.

PubMed [citation]

PMID:: 19026292

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, SCV002232528.4

#	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: 369872). This variant is also known as 1877delA. This premature translational stop signal has been observed in individual(s) with familial hypercholesterolemia (PMID: 19026292). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ala627Profs*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).

#	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: Feb 25, 2025

ClinVar

Relating variation to medicine