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NM_000527.5(LDLR):c.859G>A (p.Gly287Ser) AND Cardiovascular phenotype

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Oct 26, 2022
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:
RCV002444606.9

Allele description [Variation Report for NM_000527.5(LDLR):c.859G>A (p.Gly287Ser)]

NM_000527.5(LDLR):c.859G>A (p.Gly287Ser)

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.859G>A (p.Gly287Ser)
Other names:
NM_000527.5(LDLR):c.859G>A; p.Gly287Ser
HGVS:
  • NC_000019.10:g.11107433G>A
  • NG_009060.1:g.23053G>A
  • NM_000527.5:c.859G>AMANE SELECT
  • NM_001195798.2:c.859G>A
  • NM_001195799.2:c.736G>A
  • NM_001195800.2:c.355G>A
  • NM_001195803.2:c.478G>A
  • NP_000518.1:p.Gly287Ser
  • NP_000518.1:p.Gly287Ser
  • NP_001182727.1:p.Gly287Ser
  • NP_001182728.1:p.Gly246Ser
  • NP_001182729.1:p.Gly119Ser
  • NP_001182732.1:p.Gly160Ser
  • LRG_274t1:c.859G>A
  • LRG_274:g.23053G>A
  • LRG_274p1:p.Gly287Ser
  • NC_000019.9:g.11218109G>A
  • NM_000527.4:c.859G>A
  • c.859G>A
Protein change:
G119S
Links:
LDLR-LOVD, British Heart Foundation: LDLR_001848; dbSNP: rs375495026
NCBI 1000 Genomes Browser:
rs375495026
Molecular consequence:
  • NM_000527.5:c.859G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.859G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195799.2:c.736G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195800.2:c.355G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195803.2:c.478G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002679931Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Oct 26, 2022) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Analysis of the frequency and spectrum of mutations recognised to cause familial hypercholesterolaemia in routine clinical practice in a UK specialist hospital lipid clinic.

Futema M, Whittall RA, Kiley A, Steel LK, Cooper JA, Badmus E, Leigh SE, Karpe F, Neil HA; Simon Broome Register Group., Humphries SE.

Atherosclerosis. 2013 Jul;229(1):161-8. doi: 10.1016/j.atherosclerosis.2013.04.011. Epub 2013 Apr 18.

PubMed [citation]
PMID:
23669246
PMCID:
PMC3701838

Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction.

Do R, Stitziel NO, Won HH, Jørgensen AB, Duga S, Angelica Merlini P, Kiezun A, Farrall M, Goel A, Zuk O, Guella I, Asselta R, Lange LA, Peloso GM, Auer PL; NHLBI Exome Sequencing Project., Girelli D, Martinelli N, Farlow DN, DePristo MA, Roberts R, Stewart AF, et al.

Nature. 2015 Feb 5;518(7537):102-6. doi: 10.1038/nature13917. Epub 2014 Dec 10.

PubMed [citation]
PMID:
25487149
PMCID:
PMC4319990
See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV002679931.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

The p.G287S variant (also known as c.859G>A), located in coding exon 6 of the LDLR gene, results from a G to A substitution at nucleotide position 859. The glycine at codon 287 is replaced by serine, an amino acid with similar properties. This alteration has been reported in familial cholesterolemia (FH) cohorts; however, clinical details were limited (Futema M et al. Atherosclerosis, 2013 Jul;229:161-8; Leren TP et al. Atherosclerosis, 2021 04;322:61-66). Additionally, this alteration was reported in a control population of an early onset myocardial infarction cohort (Do R et al. Nature, 2015 Feb;518:102-6). 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 13, 2024