NM_000527.5(LDLR):c.1886del (p.Phe629fs) AND Familial hypercholesterolemia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 22, 2020
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:: RCV002229815.6

Allele description [Variation Report for NM_000527.5(LDLR):c.1886del (p.Phe629fs)]

NM_000527.5(LDLR):c.1886del (p.Phe629fs)

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.1886del (p.Phe629fs)

HGVS:

NC_000019.10:g.11120132del
NC_000019.9:g.11230805del
NG_009060.1:g.35752del
NM_000527.5:c.1886delMANE SELECT
NM_001195798.2:c.1886del
NM_001195799.2:c.1763del
NM_001195800.2:c.1382del
NM_001195803.2:c.1505del
NP_000518.1:p.Phe629fs
NP_001182727.1:p.Phe629fs
NP_001182728.1:p.Phe588fs
NP_001182729.1:p.Phe461fs
NP_001182732.1:p.Phe502fs
LRG_274:g.35752del
NC_000019.9:g.11230805del
NC_000019.9:g.11230808del
NC_000019.9:g.11230808delT
NM_000527.4:c.1886delT
c.1886delT
p.Phe629Serfs*36

Protein change:

F461fs

Links:

LDLR-LOVD, British Heart Foundation: LDLR_000261; dbSNP: rs879255068

NCBI 1000 Genomes Browser:

rs879255068

Molecular consequence:

NM_000527.5:c.1886del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195798.2:c.1886del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195799.2:c.1763del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195800.2:c.1382del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195803.2:c.1505del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

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

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SESN3 sestrin 3 [Homo sapiens]
SESN3 sestrin 3 [Homo sapiens]
Gene ID:143686

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000824578	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 22, 2020)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 17765246, 20809525, 28645073, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000824578

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 22, 2020)

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

Familial hypercholesterolaemia in Portugal.

Bourbon M, Alves AC, Medeiros AM, Silva S, Soutar AK; Investigators of Portuguese FH Study..

Atherosclerosis. 2008 Feb;196(2):633-42. Epub 2007 Aug 31.

PubMed [citation]

PMID:: 17765246

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, SCV000824578.4

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

Description

This variant has been observed in several individuals affected with familial hypercholesterolemia (PMID: 17765246, 20809525). This variant is also known as F608fsX642 in the literature. ClinVar contains an entry for this variant (Variation ID: 252104). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Phe629Serfs*36) 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). 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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