NM_000527.5(LDLR):c.1112T>C (p.Leu371Pro) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 29, 2019
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:: RCV002436373.2

Allele description [Variation Report for NM_000527.5(LDLR):c.1112T>C (p.Leu371Pro)]

NM_000527.5(LDLR):c.1112T>C (p.Leu371Pro)

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.1112T>C (p.Leu371Pro)

HGVS:

NC_000019.10:g.11111565T>C
NG_009060.1:g.27185T>C
NM_000527.5:c.1112T>CMANE SELECT
NM_001195798.2:c.1112T>C
NM_001195799.2:c.989T>C
NM_001195800.2:c.608T>C
NM_001195803.2:c.731T>C
NP_000518.1:p.Leu371Pro
NP_000518.1:p.Leu371Pro
NP_001182727.1:p.Leu371Pro
NP_001182728.1:p.Leu330Pro
NP_001182729.1:p.Leu203Pro
NP_001182732.1:p.Leu244Pro
LRG_274t1:c.1112T>C
LRG_274:g.27185T>C
LRG_274p1:p.Leu371Pro
NC_000019.9:g.11222241T>C
NM_000527.4:c.1112T>C

Protein change:

L203P

Links:

dbSNP: rs1060499920

NCBI 1000 Genomes Browser:

rs1060499920

Molecular consequence:

NM_000527.5:c.1112T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.1112T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.989T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.608T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.731T>C - 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
SCV002748970	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Apr 29, 2019)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 22081141, 28379029 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002748970

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Apr 29, 2019)

germline

clinical testing

PubMed (2)
[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

Mechanistic implications for LDL receptor degradation from the PCSK9/LDLR structure at neutral pH.

Lo Surdo P, Bottomley MJ, Calzetta A, Settembre EC, Cirillo A, Pandit S, Ni YG, Hubbard B, Sitlani A, Carfí A.

EMBO Rep. 2011 Dec 1;12(12):1300-5. doi: 10.1038/embor.2011.205.

PubMed [citation]

PMID:: 22081141
PMCID:: PMC3245695

Molecular genetic background of an autosomal dominant hypercholesterolemia in the Czech Republic.

Tichý L, Fajkusová L, Zapletalová P, Schwarzová L, Vrablík M, Freiberger T.

Physiol Res. 2017 Apr 5;66(Suppl 1):S47-S54. Review.

PubMed [citation]

PMID:: 28379029

Details of each submission

From Ambry Genetics, SCV002748970.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The p.L371P variant (also known as c.1112T>C), located in coding exon 8 of the LDLR gene, results from a T to C substitution at nucleotide position 1112. The leucine at codon 371 is replaced by proline, an amino acid with similar properties, and is located in the EGF B domain. This alteration was detected in a hypercholesterolemia cohort; however clinical details were limited (Tichý L et al. Physiol Res, 2017 Apr;66:S47-S54). Internal structural analysis suggests this alteration may be disruptive to the calcium binding EGF like domain (Lo Surdo P et al. EMBO Rep. 2011 Dec;12(12):1300-5). 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 1, 2024

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