NM_000527.5(LDLR):c.2128_2131dup (p.Cys711Ter) AND Familial hypercholesterolemia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 23, 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:: RCV001941772.6

Allele description [Variation Report for NM_000527.5(LDLR):c.2128_2131dup (p.Cys711Ter)]

NM_000527.5(LDLR):c.2128_2131dup (p.Cys711Ter)

Gene:

LDLR:low density lipoprotein receptor [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

19p13.2

Genomic location:

Preferred name:

NM_000527.5(LDLR):c.2128_2131dup (p.Cys711Ter)

HGVS:

NC_000019.10:g.11120510_11120513dup
NG_009060.1:g.36130_36133dup
NM_000527.5:c.2128_2131dupMANE SELECT
NM_001195798.2:c.2128_2131dup
NM_001195799.2:c.2005_2008dup
NM_001195800.2:c.1624_1627dup
NM_001195803.2:c.1606+277_1606+280dup
NP_000518.1:p.Cys711Ter
NP_001182727.1:p.Cys711Ter
NP_001182728.1:p.Cys670Ter
NP_001182729.1:p.Cys543Ter
LRG_274:g.36130_36133dup
NC_000019.9:g.11231185_11231186insAGCT
NC_000019.9:g.11231186_11231189dup

Protein change:

C543*

Links:

dbSNP: rs2147266606

NCBI 1000 Genomes Browser:

rs2147266606

Molecular consequence:

NM_001195803.2:c.1606+277_1606+280dup - intron variant - [Sequence Ontology: SO:0001627]
NM_000527.5:c.2128_2131dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001195798.2:c.2128_2131dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001195799.2:c.2005_2008dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001195800.2:c.1624_1627dup - nonsense - [Sequence Ontology: SO:0001587]

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
SCV002234398	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 23, 2021)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 23375686, 20809525, 28645073, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002234398

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 23, 2021)

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

Spectrum of mutations and phenotypic expression in patients with autosomal dominant hypercholesterolemia identified in Italy.

Bertolini S, Pisciotta L, Rabacchi C, Cefalù AB, Noto D, Fasano T, Signori A, Fresa R, Averna M, Calandra S.

Atherosclerosis. 2013 Apr;227(2):342-8. doi: 10.1016/j.atherosclerosis.2013.01.007. Epub 2013 Jan 19.

PubMed [citation]

PMID:: 23375686

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, SCV002234398.3

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

Description

This nonsense change has been observed in individual(s) with familial hypercholesterolemia (PMID: 23375686). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Cys711*) 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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