NM_000527.5(LDLR):c.967G>A (p.Gly323Ser) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 19, 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:: RCV003372619.2

Allele description [Variation Report for NM_000527.5(LDLR):c.967G>A (p.Gly323Ser)]

NM_000527.5(LDLR):c.967G>A (p.Gly323Ser)

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.967G>A (p.Gly323Ser)

Other names:

NM_000527.5(LDLR):c.967G>A

HGVS:

NC_000019.10:g.11110678G>A
NG_009060.1:g.26298G>A
NM_000527.5:c.967G>AMANE SELECT
NM_001195798.2:c.967G>A
NM_001195799.2:c.844G>A
NM_001195800.2:c.463G>A
NM_001195803.2:c.586G>A
NP_000518.1:p.Gly323Ser
NP_000518.1:p.Gly323Ser
NP_001182727.1:p.Gly323Ser
NP_001182728.1:p.Gly282Ser
NP_001182729.1:p.Gly155Ser
NP_001182732.1:p.Gly196Ser
LRG_274t1:c.967G>A
LRG_274:g.26298G>A
NC_000019.9:g.11221354G>A
NM_000527.4(LDLR):c.967G>A
NM_000527.4:c.967G>A
c.967G>A

Protein change:

G155S

Links:

LDLR-LOVD, British Heart Foundation: LDLR_000623; dbSNP: rs373869746

NCBI 1000 Genomes Browser:

rs373869746

Molecular consequence:

NM_000527.5:c.967G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.967G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.844G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.463G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.586G>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
SCV004087622	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Aug 19, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 15823288, 34176852, 35480308 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004087622

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Aug 19, 2023)

germline

clinical testing

PubMed (3)
[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 relationship of molecular genetic to clinical diagnosis of familial hypercholesterolemia in a Danish population.

Damgaard D, Larsen ML, Nissen PH, Jensen JM, Jensen HK, Soerensen VR, Jensen LG, Faergeman O.

Atherosclerosis. 2005 May;180(1):155-60. Epub 2005 Jan 12.

PubMed [citation]

PMID:: 15823288

Universal Screening for Familial Hypercholesterolemia in Children in Kagawa, Japan.

Matsunaga K, Mizobuchi A, Ying Fu H, Ishikawa S, Tada H, Kawashiri MA, Yokota I, Sasaki T, Ito S, Kunikata J, Iwase T, Hirao T, Yokoyama K, Hoshikawa Y, Fujisawa T, Dobashi K, Kusaka T, Minamino T.

J Atheroscler Thromb. 2022 Jun 1;29(6):839-849. doi: 10.5551/jat.62780. Epub 2021 Jun 26.

PubMed [citation]

PMID:: 34176852
PMCID:: PMC9174094

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV004087622.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The p.G323S variant (also known as c.967G>A), located in coding exon 7 of the LDLR gene, results from a G to A substitution at nucleotide position 967. The glycine at codon 323 is replaced by serine, an amino acid with similar properties. This alteration has been reported in familial hypercholesterolemia (FH) cohorts; however, clinical details were limited (Damgaard D et al. Atherosclerosis, 2005 May;180:155-60; Matsunaga K et al. J Atheroscler Thromb, 2022 Jun;29:839-849; Tada H et al. Front Genet, 2022 Apr;13:872056). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. 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: Jun 22, 2025

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