NM_000527.5(LDLR):c.2271del (p.Leu759fs) AND Cardiovascular phenotype

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 16, 2023
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:: RCV002444848.3

Allele description [Variation Report for NM_000527.5(LDLR):c.2271del (p.Leu759fs)]

NM_000527.5(LDLR):c.2271del (p.Leu759fs)

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.2271del (p.Leu759fs)

HGVS:

NC_000019.10:g.11123304del
NG_009060.1:g.38924del
NM_000527.5:c.2271delMANE SELECT
NM_001195798.2:c.2271del
NM_001195799.2:c.2148del
NM_001195800.2:c.1767del
NM_001195803.2:c.1737del
NP_000518.1:p.Leu759fs
NP_001182727.1:p.Leu759fs
NP_001182728.1:p.Leu718fs
NP_001182729.1:p.Leu591fs
NP_001182732.1:p.Leu581fs
LRG_274:g.38924del
NC_000019.9:g.11233980del
NC_000019.9:g.11233980delT
NM_000527.4:c.2271delT
NM_000527.5:c.2271del
c.2271delT

Protein change:

L581fs

Links:

LDLR-LOVD, British Heart Foundation: LDLR_000890;

Molecular consequence:

NM_000527.5:c.2271del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195798.2:c.2271del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195799.2:c.2148del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195800.2:c.1767del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195803.2:c.1737del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002733276	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Feb 16, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16314194, 21722902, 22089669, 29576406 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002733276

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Feb 16, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

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

Genetic heterogeneity of autosomal dominant hypercholesterolemia in Mexico.

Robles-Osorio L, Huerta-Zepeda A, Ordóñez ML, Canizales-Quinteros S, Díaz-Villaseñor A, Gutiérrez-Aguilar R, Riba L, Huertas-Vázquez A, Rodríguez-Torres M, Gómez-Díaz RA, Salinas S, Ongay-Larios L, Codiz-Huerta G, Mora-Cabrera M, Mehta R, Gómez Pérez FJ, Rull JA, Rabès JP, Tusié-Luna MT, Durán-Vargas S, Aguilar-Salinas CA.

Arch Med Res. 2006 Jan;37(1):102-8. Erratum in: Arch Med Res. 2006 Feb;37(2):297.

PubMed [citation]

PMID:: 16314194

Mutational analysis of the LDL receptor and APOB genes in Mexican individuals with autosomal dominant hypercholesterolemia.

Vaca G, Vàzquez A, Magaña MT, Ramìrez ML, Dàvalos IP, Martìnez E, Marìn B, Carrillo G.

Atherosclerosis. 2011 Oct;218(2):391-6. doi: 10.1016/j.atherosclerosis.2011.06.006. Epub 2011 Jun 13.

PubMed [citation]

PMID:: 21722902

See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV002733276.3

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

Description

The c.2271delT pathogenic mutation, located in coding exon 15 of the LDLR gene, results from a deletion of one nucleotide at nucleotide position 2271, causing a translational frameshift with a predicted alternate stop codon (p.L759Sfs*6). This mutation has been detected in individuals with heterozygous and homozygous familial hypercholesterolemia (FH) with co-segregation reported in multiple Mexican families (Robles-Osorio L et al. Arch. Med. Res., 2006 Jan;37:102-8; Vaca G et al. Atherosclerosis, 2011 Oct;218:391-6; Hernández Flores TJ et al. J Clin Lipidol., 2018 Mar;12:693-701). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

#	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: Jun 23, 2024

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