NM_000527.5(LDLR):c.1268T>C (p.Ile423Thr) AND Cardiovascular phenotype

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 6, 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:: RCV002446477.2

Allele description [Variation Report for NM_000527.5(LDLR):c.1268T>C (p.Ile423Thr)]

NM_000527.5(LDLR):c.1268T>C (p.Ile423Thr)

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.1268T>C (p.Ile423Thr)

HGVS:

NC_000019.10:g.11113359T>C
NG_009060.1:g.28979T>C
NM_000527.5:c.1268T>CMANE SELECT
NM_001195798.2:c.1268T>C
NM_001195799.2:c.1145T>C
NM_001195800.2:c.764T>C
NM_001195803.2:c.887T>C
NP_000518.1:p.Ile423Thr
NP_000518.1:p.Ile423Thr
NP_001182727.1:p.Ile423Thr
NP_001182728.1:p.Ile382Thr
NP_001182729.1:p.Ile255Thr
NP_001182732.1:p.Ile296Thr
LRG_274t1:c.1268T>C
LRG_274:g.28979T>C
LRG_274p1:p.Ile423Thr
NC_000019.9:g.11224035T>C
NM_000527.4:c.1268T>C
P01130:p.Ile423Thr
c.1268T>C

Protein change:

I255T

Links:

LDLR-LOVD, British Heart Foundation: LDLR_001384; UniProtKB: P01130#VAR_005382; dbSNP: rs879254849

NCBI 1000 Genomes Browser:

rs879254849

Molecular consequence:

NM_000527.5:c.1268T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.1268T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.1145T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.764T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.887T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

Recent activity

Clear Turn Off Turn On

Plec [Peromyscus leucopus]
Plec [Peromyscus leucopus]
Gene ID:114694159

Gene

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
SCV002682617	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Mar 6, 2018)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 10884919, 11005141, 12436241, 24722143 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002682617

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Mar 6, 2018)

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

Expression of an LDL receptor allele with two different mutations (E256K and I402T).

Ekström U, Abrahamson M, Sveger T, Sun XM, Soutar AK, Nilsson-Ehle P.

Mol Pathol. 2000 Feb;53(1):31-6.

PubMed [citation]

PMID:: 10884919
PMCID:: PMC1186899

Low-density lipoprotein receptor gene mutations in a Southeast Asian population with familial hypercholesterolemia.

Khoo KL, van Acker P, Defesche JC, Tan H, van de Kerkhof L, Heijnen-van Eijk SJ, Kastelein JJ, Deslypere JP.

Clin Genet. 2000 Aug;58(2):98-105.

PubMed [citation]

PMID:: 11005141

See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV002682617.2

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

Description

The p.I423T pathogenic mutation (also known as c.1268T>C), located in coding exon 9 of the LDLR gene, results from a T to C substitution at nucleotide position 1268. The isoleucine at codon 423 is replaced by threonine, an amino acid with similar properties. This alteration (historically described as p.I402T) has been reported in individuals with familial hypercholesterolemia and segregated with the disease in two apparently unrelated families (Ekström U et al. MP, Mol. Pathol., 2000 Feb;53:31-6; Khoo KL et al. Clin. Genet., 2000 Aug;58:98-105; Amsellem S et al. Hum. Genet., 2002 Dec;111:501-10; Wu WF et al. PLoS ONE, 2014 Apr;9:e94697). In addition, functional studies have suggested that this alteration would cause reduced protein activity in LDL binding and degradation (Ekström U et al. MP, Mol. Pathol., 2000 Feb;53:31-6). Based on the supporting evidence, 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: Oct 8, 2024

ClinVar

Relating variation to medicine