NM_000527.5(LDLR):c.1118G>A (p.Gly373Asp) AND Cardiovascular phenotype

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 17, 2021
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:: RCV002436075.2

Allele description [Variation Report for NM_000527.5(LDLR):c.1118G>A (p.Gly373Asp)]

NM_000527.5(LDLR):c.1118G>A (p.Gly373Asp)

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.1118G>A (p.Gly373Asp)

Other names:

FH Potenza-2

HGVS:

NC_000019.10:g.11111571G>A
NG_009060.1:g.27191G>A
NM_000527.5:c.1118G>AMANE SELECT
NM_001195798.2:c.1118G>A
NM_001195799.2:c.995G>A
NM_001195800.2:c.614G>A
NM_001195803.2:c.737G>A
NP_000518.1:p.Gly373Asp
NP_000518.1:p.Gly373Asp
NP_001182727.1:p.Gly373Asp
NP_001182728.1:p.Gly332Asp
NP_001182729.1:p.Gly205Asp
NP_001182732.1:p.Gly246Asp
LRG_274t1:c.1118G>A
LRG_274:g.27191G>A
LRG_274p1:p.Gly373Asp
NC_000019.9:g.11222247G>A
NM_000527.4:c.1118G>A
P01130:p.Gly373Asp
c.1118G>A
p.(Gly373Asp)

Protein change:

G205D

Links:

LDLR-LOVD, British Heart Foundation: LDLR_000320; UniProtKB: P01130#VAR_072845

Molecular consequence:

NM_000527.5:c.1118G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.1118G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.995G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.614G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.737G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002752727	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Nov 17, 2021)	germline	clinical testing	PubMed (13) [See all records that cite these PMIDs] 12124988, 15241806, 20091938, 21310417, 23375686, 25461735, 28958694, 30270055, 30586733, 32977124, 33258288, 34297352, 9974426 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002752727

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Nov 17, 2021)

germline

clinical testing

PubMed (13)
[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

The UMD-LDLR database: additions to the software and 490 new entries to the database.

Villéger L, Abifadel M, Allard D, Rabès JP, Thiart R, Kotze MJ, Béroud C, Junien C, Boileau C, Varret M.

Hum Mutat. 2002 Aug;20(2):81-7. Review.

PubMed [citation]

PMID:: 12124988

Molecular characterization of familial hypercholesterolemia in Spain: identification of 39 novel and 77 recurrent mutations in LDLR.

Mozas P, Castillo S, Tejedor D, Reyes G, Alonso R, Franco M, Saenz P, Fuentes F, Almagro F, Mata P, Pocoví M.

Hum Mutat. 2004 Aug;24(2):187.

PubMed [citation]

PMID:: 15241806

See all PubMed Citations (13)

Details of each submission

From Ambry Genetics, SCV002752727.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (13)

Description

The p.G373D pathogenic mutation (also known as c.1118G>A), located in coding exon 8 of the LDLR gene, results from a G to A substitution at nucleotide position 1118. The glycine at codon 373 is replaced by aspartic acid, an amino acid with similar properties. This alteration has been detected in both the homozygous and heterozygous states in multiple individuals meeting diagnostic criteria for familial hypercholesterolemia (FH) (Bertolini S et al. Arterioscler. Thromb. Vasc. Biol., 1999 Feb;19:408-18; Mozas P et al. Hum. Mutat., 2004 Aug;24:187; Noto D et al. Pediatr. Res., 2010 Feb;67:200-4; Du&scaron;ková L et al. Atherosclerosis, 2011 May;216:139-45; Jannes CE et al. Atherosclerosis, 2015 Jan;238:101-7; Scicali R et al. Nutr Metab Cardiovasc Dis, 2018 01;28:35-43; Corral P et al. Atherosclerosis, 2018 10;277:256-261; Khera AV et al. Circulation, 2019 Mar;139:1593-1602; Di Taranto MD et al. Clin Genet, 2021 11;100:529-541). In addition, this alteration is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD).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 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: Sep 29, 2024

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