NM_000527.5(LDLR):c.1207T>C (p.Phe403Leu) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 13, 2019
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:: RCV002347940.2

Allele description [Variation Report for NM_000527.5(LDLR):c.1207T>C (p.Phe403Leu)]

NM_000527.5(LDLR):c.1207T>C (p.Phe403Leu)

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.1207T>C (p.Phe403Leu)

Other names:

FH Wakayama

HGVS:

NC_000019.10:g.11113298T>C
NG_009060.1:g.28918T>C
NM_000527.5:c.1207T>CMANE SELECT
NM_001195798.2:c.1207T>C
NM_001195799.2:c.1084T>C
NM_001195800.2:c.703T>C
NM_001195803.2:c.826T>C
NP_000518.1:p.Phe403Leu
NP_000518.1:p.Phe403Leu
NP_001182727.1:p.Phe403Leu
NP_001182728.1:p.Phe362Leu
NP_001182729.1:p.Phe235Leu
NP_001182732.1:p.Phe276Leu
LRG_274t1:c.1207T>C
LRG_274:g.28918T>C
LRG_274p1:p.Phe403Leu
NC_000019.9:g.11223974T>C
NM_000527.4:c.1207T>C
P01130:p.Phe403Leu
c.1207T>C

Protein change:

F235L

Links:

LDLR-LOVD, British Heart Foundation: LDLR_000536; UniProtKB: P01130#VAR_008995; dbSNP: rs879254831

NCBI 1000 Genomes Browser:

rs879254831

Molecular consequence:

NM_000527.5:c.1207T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.1207T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.1084T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.703T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.826T>C - 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
SCV002648251	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Sep 13, 2019)	germline	clinical testing	PubMed (11) [See all records that cite these PMIDs] 10447263, 15359125, 18718593, 31491741, 32331935, 33533259, 33740630, 33794673, 34176852, 35929461, 9399845 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002648251

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Sep 13, 2019)

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

Identification of recurrent and novel mutations in the LDL receptor gene in Japanese familial hypercholesterolemia. Mutation in brief no. 248. Online.

Hattori H, Nagano M, Iwata F, Homma Y, Egashira T, Okada T.

Hum Mutat. 1999;14(1):87.

PubMed [citation]

PMID:: 10447263

Novel and recurrent mutations of the LDL receptor gene in Korean patients with familial hypercholesterolemia.

Kim JH, Choi HK, Lee H, Park HY, Kim JH, Kim JW, Kim HJ, Lee ST.

Mol Cells. 2004 Aug 31;18(1):63-70.

PubMed [citation]

PMID:: 15359125

See all PubMed Citations (11)

Details of each submission

From Ambry Genetics, SCV002648251.2

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

Description

The p.F403L variant (also known as c.1207T>C and F382L), located in coding exon 9 of the LDLR gene, results from a T to C substitution at nucleotide position 1207. The phenylalanine at codon 403 is replaced by leucine, an amino acid with highly similar properties. This alteration has been been detected in individuals from familial hypercholesterolemia cohorts; however clinical details were limited (Varret M et al. Nucleic Acids Res., 1998 Jan;26:248-52; Hattori H et al. Hum. Mutat., 1999;14:87; Kim JH et al. Mol. Cells, 2004 Aug;18:63-70; Miyake Y et al. Atherosclerosis, 2009 Mar;203:153-60). 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: Feb 25, 2025

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