NM_000527.5(LDLR):c.851G>A (p.Cys284Tyr) AND Cardiovascular phenotype

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Aug 16, 2023
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:: RCV002414422.3

Allele description [Variation Report for NM_000527.5(LDLR):c.851G>A (p.Cys284Tyr)]

NM_000527.5(LDLR):c.851G>A (p.Cys284Tyr)

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.851G>A (p.Cys284Tyr)

HGVS:

NC_000019.10:g.11107425G>A
NG_009060.1:g.23045G>A
NM_000527.5:c.851G>AMANE SELECT
NM_001195798.2:c.851G>A
NM_001195799.2:c.728G>A
NM_001195800.2:c.347G>A
NM_001195803.2:c.470G>A
NP_000518.1:p.Cys284Tyr
NP_000518.1:p.Cys284Tyr
NP_001182727.1:p.Cys284Tyr
NP_001182728.1:p.Cys243Tyr
NP_001182729.1:p.Cys116Tyr
NP_001182732.1:p.Cys157Tyr
LRG_274t1:c.851G>A
LRG_274:g.23045G>A
LRG_274p1:p.Cys284Tyr
NC_000019.9:g.11218101G>A
NM_000527.4:c.851G>A

Protein change:

C116Y

Molecular consequence:

NM_000527.5:c.851G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.851G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.728G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.347G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.470G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

Recent activity

Clear Turn Off Turn On

The effect of co-culture on MMTV-HER2 early lesion or primary tumor cell and alv...
The effect of co-culture on MMTV-HER2 early lesion or primary tumor cell and alveolar macrophages [bulk RNA-seq]
The effect of co-culture on MMTV-HER2 early lesion or primary tumor cell and alveolar macrophages [bulk RNA-seq]

BioProject

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
SCV002675455	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Aug 16, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 11310584, 15199436, 16250003, 27932355 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002675455

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Aug 16, 2023)

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

A Chinese homozygote of familial hypercholesterolemia: identification of a novel C263R mutation in the LDL receptor gene.

Wang D, Wu B, Li Y, Heng W, Zhong H, Mu Y, Wang J.

J Hum Genet. 2001;46(3):152-4.

PubMed [citation]

PMID:: 11310584

Application of molecular genetics for diagnosing familial hypercholesterolemia in Norway: results from a family-based screening program.

Leren TP, Manshaus T, Skovholt U, Skodje T, Nossen IE, Teie C, Sørensen S, Bakken KS.

Semin Vasc Med. 2004 Feb;4(1):75-85. Review.

PubMed [citation]

PMID:: 15199436

See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV002675455.3

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

Description

The p.C284Y variant (also known as c.851G>A), located in coding exon 6 of the LDLR gene, results from a G to A substitution at nucleotide position 851. The cysteine at codon 284 is replaced by tyrosine, an amino acid with highly dissimilar properties, and is located in LDLR class A repeat 7. Pathogenic LDLR mutations that result in the substitution or generation of cysteine residues within the cysteine-rich LDLR class A repeats and EGF-like domains are common in familial hypercholesterolemia (FH) (Villéger L. Hum Mutat. 2002;20(2):81-7). This particular cysteine alteration has been reported in one proband from a Chinese FH cohort (Li JJ et al. Arterioscler. Thromb. Vasc. Biol., 2017 Mar;37:570-579). This variant is also considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Internal structural analysis indicates this alteration eliminates a disulfide bond critical for the structural integrity of LDLR class A repeat 7 (Ambry internal data). Additional amino acid substitutions at this codon, p.C284R, p.C284S, and p.C284G, have also been reported in individuals with FH (Wang D et al. J. Hum. Genet., 2001;46:152-4; Leren TP et al. Semin Vasc Med, 2004 Feb;4:75-85; Fouchier SW et al. Hum. Mutat., 2005 Dec;26:550-6). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be 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: May 1, 2024

ClinVar

Relating variation to medicine