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NM_000527.5(LDLR):c.1367T>C (p.Leu456Pro) AND Cardiovascular phenotype

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jul 31, 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:
RCV002383989.3

Allele description [Variation Report for NM_000527.5(LDLR):c.1367T>C (p.Leu456Pro)]

NM_000527.5(LDLR):c.1367T>C (p.Leu456Pro)

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.1367T>C (p.Leu456Pro)
HGVS:
  • NC_000019.10:g.11113543T>C
  • NG_009060.1:g.29163T>C
  • NM_000527.5:c.1367T>CMANE SELECT
  • NM_001195798.2:c.1367T>C
  • NM_001195799.2:c.1244T>C
  • NM_001195800.2:c.863T>C
  • NM_001195803.2:c.986T>C
  • NP_000518.1:p.Leu456Pro
  • NP_000518.1:p.Leu456Pro
  • NP_001182727.1:p.Leu456Pro
  • NP_001182728.1:p.Leu415Pro
  • NP_001182729.1:p.Leu288Pro
  • NP_001182732.1:p.Leu329Pro
  • LRG_274t1:c.1367T>C
  • LRG_274:g.29163T>C
  • LRG_274p1:p.Leu456Pro
  • NC_000019.9:g.11224219T>C
  • NM_000527.4:c.1367T>C
Protein change:
L288P
Links:
dbSNP: rs200143634
NCBI 1000 Genomes Browser:
rs200143634
Molecular consequence:
  • NM_000527.5:c.1367T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.1367T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195799.2:c.1244T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195800.2:c.863T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195803.2:c.986T>C - 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
SCV002701185Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Jul 31, 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

Longitudinal evaluation and assessment of cardiovascular disease in patients with homozygous familial hypercholesterolemia.

Kolansky DM, Cuchel M, Clark BJ, Paridon S, McCrindle BW, Wiegers SE, Araujo L, Vohra Y, Defesche JC, Wilson JM, Rader DJ.

Am J Cardiol. 2008 Dec 1;102(11):1438-43. doi: 10.1016/j.amjcard.2008.07.035. Epub 2008 Sep 11.

PubMed [citation]
PMID:
19026292

Low prevalence of mutations in known loci for autosomal dominant hypercholesterolemia in a multiethnic patient cohort.

Ahmad Z, Adams-Huet B, Chen C, Garg A.

Circ Cardiovasc Genet. 2012 Dec;5(6):666-75. doi: 10.1161/CIRCGENETICS.112.963587. Epub 2012 Oct 11.

PubMed [citation]
PMID:
23064986
PMCID:
PMC3774009

Details of each submission

From Ambry Genetics, SCV002701185.3

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

Description

The p.L456P variant (also known as c.1367T>C), located in coding exon 10 of the LDLR gene, results from a T to C substitution at nucleotide position 1367. The leucine at codon 456 is replaced by proline, an amino acid with similar properties. This variant, also referred to as p.L435P, has been detected in an individual with untreated LDL-C of 279mg/dL, and co-occurred with a canonical LDLR variant in second individual reported to have homozygous familial hypercholesterolemia (Ahmad Z et al. Circ Cardiovasc Genet, 2012 Dec;5:666-75; Kolansky DM et al. Am J Cardiol, 2008 Dec;102:1438-43). This amino acid position is poorly 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: Sep 1, 2024