NM_000527.5(LDLR):c.1201C>G (p.Leu401Val) AND Cardiovascular phenotype

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jul 16, 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:: RCV002345455.9

Allele description [Variation Report for NM_000527.5(LDLR):c.1201C>G (p.Leu401Val)]

NM_000527.5(LDLR):c.1201C>G (p.Leu401Val)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

19p13.2

Genomic location:

Preferred name:

NM_000527.5(LDLR):c.1201C>G (p.Leu401Val)

HGVS:

NC_000019.10:g.11113292C>G
NG_009060.1:g.28912C>G
NM_000527.5:c.1201C>GMANE SELECT
NM_001195798.2:c.1201C>G
NM_001195799.2:c.1078C>G
NM_001195800.2:c.697C>G
NM_001195803.2:c.820C>G
NP_000518.1:p.Leu401Val
NP_000518.1:p.Leu401Val
NP_001182727.1:p.Leu401Val
NP_001182728.1:p.Leu360Val
NP_001182729.1:p.Leu233Val
NP_001182732.1:p.Leu274Val
LRG_274t1:c.1201C>G
LRG_274:g.28912C>G
LRG_274p1:p.Leu401Val
NC_000019.9:g.11223968C>G
NM_000527.4:c.1201C>G
P01130:p.Leu401Val
c.1201C>G

Protein change:

L233V

Links:

LDLR-LOVD, British Heart Foundation: LDLR_000535; UniProtKB: P01130#VAR_007987

Molecular consequence:

NM_000527.5:c.1201C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.1201C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.1078C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.697C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.820C>G - missense variant - [Sequence Ontology: SO:0001583]

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
SCV002650517	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Jul 16, 2021)	germline	clinical testing	PubMed (11) [See all records that cite these PMIDs] 21722902, 21957200, 22683370, 23669246, 24507775, 25461735, 25637381, 30586733, 31447099, 32041611, 9104431 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002650517

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Jul 16, 2021)

germline

clinical testing

PubMed (11)
[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

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

LDL-apheresis depletes apoE-HDL and pre-β1-HDL in familial hypercholesterolemia: relevance to atheroprotection.

Orsoni A, Saheb S, Levels JHM, Dallinga-Thie G, Atassi M, Bittar R, Robillard P, Bruckert E, Kontush A, Carrié A, Chapman MJ.

J Lipid Res. 2011 Dec;52(12):2304-2313. doi: 10.1194/jlr.P016816. Epub 2011 Sep 26.

PubMed [citation]

PMID:: 21957200
PMCID:: PMC3283261

See all PubMed Citations (11)

Details of each submission

From Ambry Genetics, SCV002650517.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (11)

Description

The p.L401V variant (also known as c.1201C>G), located in coding exon 9 of the LDLR gene, results from a C to G substitution at nucleotide position 1201. The leucine at codon 401 is replaced by valine, an amino acid with highly similar properties. This alteration, also referred to as L380V, has been reported in hypercholesterolemia and early onset myocardial infarction cohorts (Leren TP et al. J. Intern. Med., 1997 Mar;241:185-94; Vaca G et al. Atherosclerosis, 2011 Oct;218:391-6; Lange LA et al. Am. J. Hum. Genet., 2014 Feb;94:233-45; Jannes CE et al. Atherosclerosis, 2015 Jan;238:101-7; Khera AV et al. Circulation, 2019 03;139:1593-1602). This alteration was also described to segregate with the disease (Leren TP et al. J. Intern. Med., 1997 Mar;241:185-94). This variant has been seen in an exome cohort, but cardiovascular history was not provided (Amendola LM et al. Genome Res., 2015 Mar;25:305-15). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be 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: Nov 3, 2024

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