NM_000527.5(LDLR):c.2113G>T (p.Ala705Ser) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 2, 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:: RCV003372667.2

Allele description [Variation Report for NM_000527.5(LDLR):c.2113G>T (p.Ala705Ser)]

NM_000527.5(LDLR):c.2113G>T (p.Ala705Ser)

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.2113G>T (p.Ala705Ser)

Other names:

NM_000527.5(LDLR):c.2113G>T; p.Ala705Ser

HGVS:

NC_000019.10:g.11120495G>T
NG_009060.1:g.36115G>T
NM_000527.5:c.2113G>TMANE SELECT
NM_001195798.2:c.2113G>T
NM_001195799.2:c.1990G>T
NM_001195800.2:c.1609G>T
NM_001195803.2:c.1606+262G>T
NP_000518.1:p.Ala705Ser
NP_000518.1:p.Ala705Ser
NP_001182727.1:p.Ala705Ser
NP_001182728.1:p.Ala664Ser
NP_001182729.1:p.Ala537Ser
LRG_274t1:c.2113G>T
LRG_274:g.36115G>T
LRG_274p1:p.Ala705Ser
NC_000019.9:g.11231171G>T
NM_000527.4:c.2113G>T
c.2113G>T

Protein change:

A537S

Links:

LDLR-LOVD, British Heart Foundation: LDLR_000986; dbSNP: rs193922570

NCBI 1000 Genomes Browser:

rs193922570

Molecular consequence:

NM_001195803.2:c.1606+262G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_000527.5:c.2113G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.2113G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.1990G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.1609G>T - 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
SCV004087503	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Sep 2, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 15556093, 17142622, 18325082, 19837725, 30778614, 33303402 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004087503

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Sep 2, 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

Mutation detection in patients with familial hypercholesterolaemia using heteroduplex and single strand conformation polymorphism analysis by capillary electrophoresis.

Sozen M, Whittall R, Humphries SE.

Atheroscler Suppl. 2004 Dec;5(5):7-11.

PubMed [citation]

PMID:: 15556093

Genetic causes of familial hypercholesterolaemia in patients in the UK: relation to plasma lipid levels and coronary heart disease risk.

Humphries SE, Whittall RA, Hubbart CS, Maplebeck S, Cooper JA, Soutar AK, Naoumova R, Thompson GR, Seed M, Durrington PN, Miller JP, Betteridge DJ, Neil HA; Simon Broome Familial Hyperlipidaemia Register Group and Scientific Steering Committee..

J Med Genet. 2006 Dec;43(12):943-9. Erratum in: J Med Genet. 2009 Dec;46(12):861. J Med Genet. 2010 Dec;47(12):862.

PubMed [citation]

PMID:: 17142622
PMCID:: PMC2563208

See all PubMed Citations (6)

Details of each submission

From Ambry Genetics, SCV004087503.2

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

Description

The p.A705S variant (also known as c.2113G>T), located in coding exon 14 of the LDLR gene, results from a G to T substitution at nucleotide position 2113. The alanine at codon 705 is replaced by serine, an amino acid with similar properties. This alteration has been reported in subjects with familial hypercholesterolemia (FH) (Humphries SE et al. J Med Genet, 2006 Dec;43:943-9; Sozen M et al. Atheroscler Suppl, 2004 Dec;5:7-11; Whittall RA et al. Ann Clin Biochem, 2010 Jan;47:44-55; Gill PK et al. J Clin Lipidol, 2021 Nov;15:79-87). This amino acid position is not well 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: May 7, 2024

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