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NM_000527.5(LDLR):c.758G>A (p.Arg253Gln) AND Cardiovascular phenotype

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Oct 24, 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:
RCV004031422.1

Allele description [Variation Report for NM_000527.5(LDLR):c.758G>A (p.Arg253Gln)]

NM_000527.5(LDLR):c.758G>A (p.Arg253Gln)

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.758G>A (p.Arg253Gln)
Other names:
NM_000527.5(LDLR):c.758G>A; p.Arg253Gln
HGVS:
  • NC_000019.10:g.11106628G>A
  • NG_009060.1:g.22248G>A
  • NM_000527.5:c.758G>AMANE SELECT
  • NM_001195798.2:c.758G>A
  • NM_001195799.2:c.635G>A
  • NM_001195800.2:c.314-764G>A
  • NM_001195803.2:c.377G>A
  • NP_000518.1:p.Arg253Gln
  • NP_001182727.1:p.Arg253Gln
  • NP_001182728.1:p.Arg212Gln
  • NP_001182732.1:p.Arg126Gln
  • LRG_274t1:c.758G>A
  • LRG_274:g.22248G>A
  • NC_000019.9:g.11217304G>A
  • NC_000019.9:g.11217304G>A
  • NM_000527.4:c.758G>A
Protein change:
R126Q
Links:
dbSNP: rs139507589
NCBI 1000 Genomes Browser:
rs139507589
Molecular consequence:
  • NM_001195800.2:c.314-764G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000527.5:c.758G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.758G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195799.2:c.635G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195803.2:c.377G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV005035889Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Oct 24, 2023) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Clinical Evaluation of Patients with Genetically Confirmed Familial Hypercholesterolemia.

Aparicio A, Villazón F, Suárez-Gutiérrez L, Gómez J, Martínez-Faedo C, Méndez-Torre E, Avanzas P, Álvarez-Velasco R, Cuesta-Llavona E, García-Lago C, Neuhalfen D, Coto E, Lorca R.

J Clin Med. 2023 Jan 29;12(3). doi:pii: 1030. 10.3390/jcm12031030.

PubMed [citation]
PMID:
36769678
PMCID:
PMC9917940

Details of each submission

From Ambry Genetics, SCV005035889.1

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

Description

The p.R253Q variant (also known as c.758G>A), located in coding exon 5 of the LDLR gene, results from a G to A substitution at nucleotide position 758. The arginine at codon 253 is replaced by glutamine, an amino acid with highly similar properties. This variant co-occurred with a pathogenic mutation in the LDLR gene in an individual from a familial hypercholesterolemia cohort (Aparicio A et al. J Clin Med, 2023 Jan;12). 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.

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

Last Updated: Sep 29, 2024