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NM_000527.5(LDLR):c.1503G>A (p.Ala501=) AND Cardiovascular phenotype

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Mar 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:
RCV003298316.2

Allele description [Variation Report for NM_000527.5(LDLR):c.1503G>A (p.Ala501=)]

NM_000527.5(LDLR):c.1503G>A (p.Ala501=)

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.1503G>A (p.Ala501=)
Other names:
NM_000527.5(LDLR):c.1503G>A
HGVS:
  • NC_000019.10:g.11113679G>A
  • NG_009060.1:g.29299G>A
  • NM_000527.5:c.1503G>AMANE SELECT
  • NM_001195798.2:c.1503G>A
  • NM_001195799.2:c.1380G>A
  • NM_001195800.2:c.999G>A
  • NM_001195803.2:c.1122G>A
  • NP_000518.1:p.Ala501=
  • NP_000518.1:p.Ala501=
  • NP_001182727.1:p.Ala501=
  • NP_001182728.1:p.Ala460=
  • NP_001182729.1:p.Ala333=
  • NP_001182732.1:p.Ala374=
  • LRG_274t1:c.1503G>A
  • LRG_274:g.29299G>A
  • NC_000019.9:g.11224355G>A
  • NM_000527.4(LDLR):c.1503G>A
  • NM_000527.4:c.1503G>A
  • c.1503G>A
  • p.Ala501=
Links:
LDLR-LOVD, British Heart Foundation: LDLR_000208; dbSNP: rs368889457
NCBI 1000 Genomes Browser:
rs368889457
Molecular consequence:
  • NM_000527.5:c.1503G>A - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001195798.2:c.1503G>A - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001195799.2:c.1380G>A - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001195800.2:c.999G>A - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001195803.2:c.1122G>A - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004000122Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Mar 19, 2023) 		germlineclinical testing

PubMed (2)
[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

Molecular characterization of Polish patients with familial hypercholesterolemia: novel and recurrent LDLR mutations.

Chmara M, Wasag B, Zuk M, Kubalska J, Wegrzyn A, Bednarska-Makaruk M, Pronicka E, Wehr H, Defesche JC, Rynkiewicz A, Limon J.

J Appl Genet. 2010;51(1):95-106. doi: 10.1007/BF03195716.

PubMed [citation]
PMID:
20145306

Autosomal dominant hypercholesterolemia in Catalonia: Correspondence between clinical-biochemical and genetic diagnostics in 967 patients studied in a multicenter clinical setting.

Martín-Campos JM, Plana N, Figueras R, Ibarretxe D, Caixàs A, Esteve E, Pérez A, Bueno M, Mauri M, Roig R, Martínez S, Pintó X, Masana L, Julve J, Blanco-Vaca F; Xarxa d’Unitats de Lípids i Arteriosclerosi (XULA)..

J Clin Lipidol. 2018 Nov - Dec;12(6):1452-1462. doi: 10.1016/j.jacl.2018.09.002. Epub 2018 Sep 7.

PubMed [citation]
PMID:
30293936

Details of each submission

From Ambry Genetics, SCV004000122.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

The c.1503G>A variant (also known as p.A501A), located in coding exon 10 of the LDLR gene, results from a G to A substitution at nucleotide position 1503. This nucleotide substitution does not change the alanine at codon 501. This alteration has been reported in familial hypercholesterolemia (FH) cohorts; however, clinical details were limited (Chmara M et al. J Appl Genet, 2010;51:95-106; Martín-Campos JM et al. J Clin Lipidol, 2018 Sep;12:1452-1462). This nucleotide position is poorly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will result in the creation or strengthening of a novel splice acceptor site. 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: Sep 29, 2024