NM_000527.5(LDLR):c.1723C>T (p.Leu575Phe) AND Familial hypercholesterolemia

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Aug 2, 2022
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:: RCV003581672.1

Allele description [Variation Report for NM_000527.5(LDLR):c.1723C>T (p.Leu575Phe)]

NM_000527.5(LDLR):c.1723C>T (p.Leu575Phe)

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.1723C>T (p.Leu575Phe)

HGVS:

NC_000019.10:g.11116876C>T
NG_009060.1:g.32496C>T
NM_000527.5:c.1723C>TMANE SELECT
NM_001195798.2:c.1723C>T
NM_001195799.2:c.1600C>T
NM_001195800.2:c.1219C>T
NM_001195803.2:c.1342C>T
NP_000518.1:p.Leu575Phe
NP_000518.1:p.Leu575Phe
NP_001182727.1:p.Leu575Phe
NP_001182728.1:p.Leu534Phe
NP_001182729.1:p.Leu407Phe
NP_001182732.1:p.Leu448Phe
LRG_274t1:c.1723C>T
LRG_274:g.32496C>T
LRG_274p1:p.Leu575Phe
NC_000019.9:g.11227552C>T
NM_000527.4(LDLR):c.1723C>T
NM_000527.4:c.1723C>T
p.Leu575Phe

Protein change:

L407F

Links:

dbSNP: rs1205480064

NCBI 1000 Genomes Browser:

rs1205480064

Molecular consequence:

NM_000527.5:c.1723C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.1723C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.1600C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.1219C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.1342C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Familial hypercholesterolemia
Identifiers:: MONDO: MONDO:0005439; MedGen: C0020445; OMIM: PS143890

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004358543	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Aug 2, 2022)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 27830735, 28502495, 29874871, 33747976, 33994402, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004358543

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Aug 2, 2022)

germline

clinical testing

PubMed (6)
[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

The use of targeted exome sequencing in genetic diagnosis of young patients with severe hypercholesterolemia.

Jiang L, Wu WF, Sun LY, Chen PP, Wang W, Benito-Vicente A, Zhang F, Pan XD, Cui W, Yang SW, Zhou YJ, Martin C, Wang LY.

Sci Rep. 2016 Nov 10;6:36823. doi: 10.1038/srep36823.

PubMed [citation]

PMID:: 27830735
PMCID:: PMC5103295

Detection of common sequence variations of familial hypercholesterolemia in Taiwan using DNA mass spectrometry.

Chiou KR, Charng MJ.

J Clin Lipidol. 2017 Mar - Apr;11(2):386-393.e6. doi: 10.1016/j.jacl.2016.12.014. Epub 2017 Jan 10.

PubMed [citation]

PMID:: 28502495

See all PubMed Citations (6)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV004358543.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This missense variant (also known as p.Leu554Phe in the mature protein) replaces leucine with phenylalanine at codon 575 in the LDLR type B repeat 5 of the EGF precursor homology domain of the LDLR protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Functional studies have shown that this variant causes a defect in protein trafficking and results in reduced cell-surface expression of LDLR and diminished LDL binding/uptake activities (PMID: 27830735, 29874871). This variant has been reported in at least 6 unrelated individuals affected with familial hypercholesterolemia (PMID: 27830735, 28502495, 33994402, 33747976). It has been shown that this variant segregates with elevated LDL-C levels in a family with myocardial infarction, hyperlipidemia, hypertension, and type 2 diabetes mellitus (PMID: 33747976). This variant has been identified in 1/251486 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Likely 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 1, 2024

ClinVar

Relating variation to medicine