NM_000527.5(LDLR):c.269A>G (p.Asp90Gly) AND Cardiovascular phenotype

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 25, 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:: RCV002426991.2

Allele description [Variation Report for NM_000527.5(LDLR):c.269A>G (p.Asp90Gly)]

NM_000527.5(LDLR):c.269A>G (p.Asp90Gly)

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.269A>G (p.Asp90Gly)

Other names:

FH London-4; NM_000527.5(LDLR):c.269A>G

HGVS:

NC_000019.10:g.11102742A>G
NG_009060.1:g.18362A>G
NM_000527.5:c.269A>GMANE SELECT
NM_001195798.2:c.269A>G
NM_001195799.2:c.190+2397A>G
NM_001195800.2:c.269A>G
NM_001195803.2:c.269A>G
NP_000518.1:p.Asp90Gly
NP_000518.1:p.Asp90Gly
NP_001182727.1:p.Asp90Gly
NP_001182729.1:p.Asp90Gly
NP_001182732.1:p.Asp90Gly
LRG_274t1:c.269A>G
LRG_274:g.18362A>G
LRG_274p1:p.Asp90Gly
NC_000019.9:g.11213418A>G
NM_000527.4:c.269A>G
P01130:p.Asp90Gly
c.269A>G

Protein change:

D90G

Links:

LDLR-LOVD, British Heart Foundation: LDLR_001676; UniProtKB: P01130#VAR_005310; dbSNP: rs771019366

NCBI 1000 Genomes Browser:

rs771019366

Molecular consequence:

NM_001195799.2:c.190+2397A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000527.5:c.269A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.269A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.269A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.269A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

Recent activity

Clear Turn Off Turn On

LOC114276977 [Camellia sinensis]
LOC114276977 [Camellia sinensis]
Gene ID:114276977

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
SCV002743473	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (May 25, 2023)	germline	clinical testing	PubMed (11) [See all records that cite these PMIDs] 1301956, 8347689, 9026534, 9259195, 10933493, 11857755, 12436241, 19026292, 20809525, 22883975, 25487149 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002743473

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(May 25, 2023)

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

Molecular genetics of the LDL receptor gene in familial hypercholesterolemia.

Hobbs HH, Brown MS, Goldstein JL.

Hum Mutat. 1992;1(6):445-66. Review.

PubMed [citation]

PMID:: 1301956

Identification of two new LDL-receptor mutations causing homozygous familial hypercholesterolemia in a South African of Indian origin.

Rubinsztein DC, Jialal I, Leitersdorf E, Coetzee GA, van der Westhuyzen DR.

Biochim Biophys Acta. 1993 Aug 4;1182(1):75-82.

PubMed [citation]

PMID:: 8347689

See all PubMed Citations (11)

Details of each submission

From Ambry Genetics, SCV002743473.2

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

Description

The c.269A>G (p.D90G) alteration is located in coding exon 3 of the LDLR gene. This alteration results from a A to G substitution at nucleotide position 269, causing the aspartic acid (D) at amino acid position 90 to be replaced by a glycine (G). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This alteration, also known as FH London-4 and D69G, has been reported in hypercholesterolemia patients from various ethnic groups (Hobbs, 1992; Webb, 1996; Day, 1997; Bunn, 2002; Amsellem, 2002; Hooper, 2012). Other alterations at the same codon, p.D90N and p.D90E, have also reported in association with hypercholesterolemia (Day, 1997; Marduel, 2010). This amino acid position is highly conserved in available vertebrate species. Based on internal structural analysis, this variant is predicted to be structurally disruptive (Kurniawan, 2000). This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as 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 29, 2024

ClinVar

Relating variation to medicine