NM_000527.5(LDLR):c.227_233del (p.Gly76fs) AND Familial hypercholesterolemia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 31, 2021
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:: RCV002568932.2

Allele description [Variation Report for NM_000527.5(LDLR):c.227_233del (p.Gly76fs)]

NM_000527.5(LDLR):c.227_233del (p.Gly76fs)

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.227_233del (p.Gly76fs)

HGVS:

NC_000019.10:g.11102700_11102706del
NG_009060.1:g.18320_18326del
NM_000527.5:c.227_233delMANE SELECT
NM_001195798.2:c.227_233del
NM_001195799.2:c.190+2355_190+2361del
NM_001195800.2:c.227_233del
NM_001195803.2:c.227_233del
NP_000518.1:p.Gly76fs
NP_001182727.1:p.Gly76fs
NP_001182729.1:p.Gly76fs
NP_001182732.1:p.Gly76fs
LRG_274t1:c.227_233del
LRG_274:g.18320_18326del
NC_000019.9:g.11213375_11213381del
NC_000019.9:g.11213376_11213382del
NM_000527.4:c.227_233delGGGGCCG

Protein change:

G76fs

Links:

dbSNP: rs2147216927

NCBI 1000 Genomes Browser:

rs2147216927

Molecular consequence:

NM_000527.5:c.227_233del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195798.2:c.227_233del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195800.2:c.227_233del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195803.2:c.227_233del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195799.2:c.190+2355_190+2361del - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Familial hypercholesterolemia (FH)
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
SCV003317148	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 31, 2021)	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

SCV003317148

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 31, 2021)

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, SCV003317148.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1180494). 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 sequence change creates a premature translational stop signal (p.Gly76Valfs*128) 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 20, 2024

ClinVar

Relating variation to medicine