NM_000527.5(LDLR):c.340T>A (p.Phe114Ile) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 27, 2018
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:: RCV002451333.2

Allele description [Variation Report for NM_000527.5(LDLR):c.340T>A (p.Phe114Ile)]

NM_000527.5(LDLR):c.340T>A (p.Phe114Ile)

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.340T>A (p.Phe114Ile)

HGVS:

NC_000019.10:g.11105246T>A
NG_009060.1:g.20866T>A
NM_000527.5:c.340T>AMANE SELECT
NM_001195798.2:c.340T>A
NM_001195799.2:c.217T>A
NM_001195800.2:c.314-2146T>A
NM_001195803.2:c.314-1319T>A
NP_000518.1:p.Phe114Ile
NP_001182727.1:p.Phe114Ile
NP_001182728.1:p.Phe73Ile
LRG_274t1:c.340T>A
LRG_274:g.20866T>A
NC_000019.9:g.11215922T>A
NM_000527.4:c.340T>A

Protein change:

F114I

Links:

dbSNP: rs776716507

NCBI 1000 Genomes Browser:

rs776716507

Molecular consequence:

NM_001195800.2:c.314-2146T>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001195803.2:c.314-1319T>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000527.5:c.340T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.340T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.217T>A - 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
SCV002614371	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Jul 27, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002614371

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Jul 27, 2018)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Efficacy of alirocumab in 1191 patients with a wide spectrum of mutations in genes causative for familial hypercholesterolemia.

Defesche JC, Stefanutti C, Langslet G, Hopkins PN, Seiz W, Baccara-Dinet MT, Hamon SC, Banerjee P, Kastelein JJP.

J Clin Lipidol. 2017 Nov - Dec;11(6):1338-1346.e7. doi: 10.1016/j.jacl.2017.08.016. Epub 2017 Sep 4. Erratum in: J Clin Lipidol. 2020 Sep - Oct;14(5):742. doi: 10.1016/j.jacl.2020.09.010.

PubMed [citation]

PMID:: 28964736

Details of each submission

From Ambry Genetics, SCV002614371.2

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

Description

The p.F114I variant (also known as c.340T>A), located in coding exon 4 of the LDLR gene, results from a T to A substitution at nucleotide position 340. The phenylalanine at codon 114 is replaced by isoleucine, an amino acid with highly similar properties. This alteration was detected in an individual with elevated LDL and a familial hypercholesterolemia (FH) diagnosis; however, additional clinical details were not provided (Defesche JC et al. J Clin Lipidol Sep;11:1338-1346.e7). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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: May 1, 2024

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