NM_000527.5(LDLR):c.1546G>A (p.Gly516Ser) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 22, 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:: RCV002399777.10

Allele description [Variation Report for NM_000527.5(LDLR):c.1546G>A (p.Gly516Ser)]

NM_000527.5(LDLR):c.1546G>A (p.Gly516Ser)

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.1546G>A (p.Gly516Ser)

HGVS:

NC_000019.10:g.11113722G>A
NG_009060.1:g.29342G>A
NM_000527.5:c.1546G>AMANE SELECT
NM_001195798.2:c.1546G>A
NM_001195799.2:c.1423G>A
NM_001195800.2:c.1042G>A
NM_001195803.2:c.1165G>A
NP_000518.1:p.Gly516Ser
NP_000518.1:p.Gly516Ser
NP_001182727.1:p.Gly516Ser
NP_001182728.1:p.Gly475Ser
NP_001182729.1:p.Gly348Ser
NP_001182732.1:p.Gly389Ser
LRG_274t1:c.1546G>A
LRG_274:g.29342G>A
LRG_274p1:p.Gly516Ser
NC_000019.9:g.11224398G>A
NM_000527.4:c.1546G>A
c.1546G>A

Protein change:

G348S

Links:

LDLR-LOVD, British Heart Foundation: LDLR_001452;

Molecular consequence:

NM_000527.5:c.1546G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.1546G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.1423G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.1042G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.1165G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

Recent activity

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cylicin-2 isoform X1 [Oryctolagus cuniculus]
cylicin-2 isoform X1 [Oryctolagus cuniculus]
gi|655599556|ref|XP_008256622.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002706299	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Mar 22, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 20809525, 22883975, 25487149, 29399563, 31491741, 33303402 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002706299

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Mar 22, 2023)

germline

clinical testing

PubMed (6)
[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 spectrum of autosomal dominant hypercholesterolemia in France.

Marduel M, Carrié A, Sassolas A, Devillers M, Carreau V, Di Filippo M, Erlich D, Abifadel M, Marques-Pinheiro A, Munnich A, Junien C; French ADH Research Network., Boileau C, Varret M, Rabès JP.

Hum Mutat. 2010 Nov;31(11):E1811-24. doi: 10.1002/humu.21348.

PubMed [citation]

PMID:: 20809525
PMCID:: PMC3152176

Genetic analysis of familial hypercholesterolaemia in Western Australia.

Hooper AJ, Nguyen LT, Burnett JR, Bates TR, Bell DA, Redgrave TG, Watts GF, van Bockxmeer FM.

Atherosclerosis. 2012 Oct;224(2):430-4. doi: 10.1016/j.atherosclerosis.2012.07.030. Epub 2012 Jul 27.

PubMed [citation]

PMID:: 22883975

See all PubMed Citations (6)

Details of each submission

From Ambry Genetics, SCV002706299.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

The p.G516S variant (also known as c.1546G>A), located in coding exon 10 of the LDLR gene, results from a G to A substitution at nucleotide position 1546. The glycine at codon 516 is replaced by serine, an amino acid with similar properties. This variant has been reported in hypercholesterolemia and early onset myocardial infarction cohorts; however, it was also detected in two controls and clinical details were limited in most cases (Marduel M et al. Hum. Mutat., 2010 Nov;31:E1811-24; Hooper AJ et al. Atherosclerosis, 2012 Oct;224:430-4; Do R et al. Nature, 2015 Feb;518:102-6; Kim HN et al. Chonnam Med J, 2018 Jan;54:31-35). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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: Nov 3, 2024

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