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

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 4, 2020
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:: RCV001384956.7

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

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
SCV001584659	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 4, 2020)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 7635461, 24722143, 11005141, 10884919, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001584659

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 4, 2020)

germline

clinical testing

PubMed (5)
[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

An efficient screening procedure detecting six novel mutations in the LDL receptor gene in Swedish children with hypercholesterolemia.

Ekström U, Abrahamson M, Sveger T, Lombardi P, Nilsson-Ehle P.

Hum Genet. 1995 Aug;96(2):147-50.

PubMed [citation]

PMID:: 7635461

Use of targeted exome sequencing in genetic diagnosis of Chinese familial hypercholesterolemia.

Wu WF, Sun LY, Pan XD, Yang SW, Wang LY.

PLoS One. 2014;9(4):e94697. doi: 10.1371/journal.pone.0094697.

PubMed [citation]

PMID:: 24722143
PMCID:: PMC3983231

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001584659.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. This variant has been reported to affect LDLR protein function (PMID: 10884919). This variant has been observed in individual(s) with familial hypercholesterolemia (PMID: 7635461, 24722143, 11005141, 10884919, Invitae). It has also been observed to segregate with disease in related individuals. This variant is also known as p.I402T in the literature. ClinVar contains an entry for this variant (Variation ID: 251760, 430765). This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with threonine at codon 423 of the LDLR protein (p.Ile423Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine.

#	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