NM_000527.5(LDLR):c.1775G>A (p.Gly592Glu) AND Cardiovascular phenotype

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 21, 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:: RCV002399517.9

Allele description [Variation Report for NM_000527.5(LDLR):c.1775G>A (p.Gly592Glu)]

NM_000527.5(LDLR):c.1775G>A (p.Gly592Glu)

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.1775G>A (p.Gly592Glu)

Other names:

FH Sicily; FH Foggia-1; FH Naples4; FH Sicilia-4; NP_000518.1:p.G592E; NM_000527.5(LDLR):c.1775G>A

HGVS:

NC_000019.10:g.11116928G>A
NG_009060.1:g.32548G>A
NM_000527.5:c.1775G>AMANE SELECT
NM_001195798.2:c.1775G>A
NM_001195799.2:c.1652G>A
NM_001195800.2:c.1271G>A
NM_001195803.2:c.1394G>A
NP_000518.1:p.Gly592Glu
NP_000518.1:p.Gly592Glu
NP_001182727.1:p.Gly592Glu
NP_001182728.1:p.Gly551Glu
NP_001182729.1:p.Gly424Glu
NP_001182732.1:p.Gly465Glu
LRG_274t1:c.1775G>A
LRG_274:g.32548G>A
LRG_274p1:p.Gly592Glu
NC_000019.9:g.11227604G>A
NM_000527.4:c.1775G>A
P01130:p.Gly592Glu
c.1775G>A
p.(Gly592Glu)

Protein change:

G424E

Links:

LDLR-LOVD, British Heart Foundation: LDLR_000237; UniProtKB: P01130#VAR_005403

Molecular consequence:

NM_000527.5:c.1775G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.1775G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.1652G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.1271G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.1394G>A - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

no known functional consequence - Comment(s)
- non-disruptive missense
variation affecting protein function [Variation Ontology: 0003]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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ATP5MJ ATP synthase membrane subunit j [Homo sapiens]
ATP5MJ ATP synthase membrane subunit j [Homo sapiens]
Gene ID:9556

Gene
9556[uid] AND (alive[prop]) (1)
Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002714823	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Sep 21, 2021)	germline	clinical testing	PubMed (21) [See all records that cite these PMIDs] 11317361, 15864114, 17765246, 20145306, 20663204, 21310417, 21865347, 21925044, 22390909, 23375686, 25461735, 25487149, 25647241, 25936317, 26020417, 26036859, 26238499, 26723464, 27824480, 27998977, 31617323 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002714823

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Sep 21, 2021)

germline

clinical testing

PubMed (21)
[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

Characterization and geographic distribution of the low density lipoprotein receptor (LDLR) gene mutations in northwestern Greece.

Miltiadous G, Elisaf M, Bairaktari H, Xenophontos SL, Manoli P, Cariolou MA.

Hum Mutat. 2001 May;17(5):432-3.

PubMed [citation]

PMID:: 11317361

Genetic and environmental factors affecting the response to statin therapy in patients with molecularly defined familial hypercholesterolaemia.

Miltiadous G, Xenophontos S, Bairaktari E, Ganotakis M, Cariolou M, Elisaf M.

Pharmacogenet Genomics. 2005 Apr;15(4):219-25.

PubMed [citation]

PMID:: 15864114

See all PubMed Citations (21)

Details of each submission

From Ambry Genetics, SCV002714823.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (21)

Description

The p.G592E pathogenic mutation (also known as c.1775G>A), located in coding exon 12 of the LDLR gene, results from a G to A substitution at nucleotide position 1775. The glycine at codon 592 is replaced by glutamic acid, an amino acid with some similar properties, and is located in the EGF precursor-like domain. This mutation, also known as FH-Sicily and G571E, has been detected in many unrelated individuals with familial hypercholesterolemia (FH), and has also been reported to impact protein function (Hobbs et al. Hum Mutat. 1992;1(6):445-66; Miltiadous G et al. Hum Mutat. 2001;17(5):432-3; Romano M et al. J Lipid Res. 2011;52(11):2095-100; Susan-Resiga D et al. J Biol Chem. 2017;292(5):1573-1590). In addition, this mutation has been reported as one of the most common amongst Czech, Polish, German, Austrian, and Slovak FH cohorts (Chmara M et al. J Appl Genet. 2010;51(1):95-106; Tichy et al. Atherosclerosis. 2012;223(2):401-8; Gabová D et al. Physiol Res. 2017;66(1):75-84). 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 26, 2024

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