NM_000527.5(LDLR):c.542C>G (p.Pro181Arg) AND not provided

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: May 24, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000161959.4

Allele description [Variation Report for NM_000527.5(LDLR):c.542C>G (p.Pro181Arg)]

NM_000527.5(LDLR):c.542C>G (p.Pro181Arg)

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.542C>G (p.Pro181Arg)

Other names:

NM_000527.5(LDLR):c.542C>G

HGVS:

NC_000019.10:g.11105448C>G
NG_009060.1:g.21068C>G
NM_000527.5:c.542C>GMANE SELECT
NM_001195798.2:c.542C>G
NM_001195799.2:c.419C>G
NM_001195800.2:c.314-1944C>G
NM_001195803.2:c.314-1117C>G
NP_000518.1:p.Pro181Arg
NP_000518.1:p.Pro181Arg
NP_001182727.1:p.Pro181Arg
NP_001182728.1:p.Pro140Arg
LRG_274t1:c.542C>G
LRG_274:g.21068C>G
LRG_274p1:p.Pro181Arg
NC_000019.9:g.11216124C>G
NM_000527.4:c.542C>G
c.542C>G
p.(Pro181Arg)

Protein change:

P140R

Links:

LDLR-LOVD, British Heart Foundation: LDLR_000361; dbSNP: rs557344672

NCBI 1000 Genomes Browser:

rs557344672

Molecular consequence:

NM_001195800.2:c.314-1944C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001195803.2:c.314-1117C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000527.5:c.542C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.542C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.419C>G - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

no known functional consequence - Comment(s)

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000189534	Dept. of Genetics and Pharmacogenomics, Merck Research Labs	no classification provided (in vitro)	not provided	not applicable	in vitro	PubMed (1) [See all records that cite this PMID]
SCV001469531	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (Jul 24, 2020)	unknown	clinical testing	PubMed (11) [See all records that cite these PMIDs] 11754108, 21868016, 23375686, 25647241, 25487149, 22698793, 20045108, 18279815, 16250003, 14508510, 26467025
SCV005078058	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (May 24, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000189534

Dept. of Genetics and Pharmacogenomics, Merck Research Labs

no classification provided

(in vitro)

not provided

not applicable

in vitro

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

SCV001469531

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Uncertain significance
(Jul 24, 2020)

unknown

clinical testing

PubMed (11)
[See all records that cite these PMIDs]

SCV005078058

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(May 24, 2024)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	not applicable	not applicable	not provided	not provided	not provided	not provided	not provided	in vitro
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Spectrum of low density lipoprotein receptor mutations in Czech hypercholesterolemic patients.

Kuhrová V, Francová H, Zapletalová P, Freiberger T, Fajkusová L, Hrabincová E, Slováĉková R, Kozák L, Slováková R.

Hum Mutat. 2002 Jan;19(1):80.

PubMed [citation]

PMID:: 11754108

Reduced penetrance of autosomal dominant hypercholesterolemia in a high percentage of families: importance of genetic testing in the entire family.

Garcia-Garcia AB, Ivorra C, Martinez-Hervas S, Blesa S, Fuentes MJ, Puig O, Martín-de-Llano JJ, Carmena R, Real JT, Chaves FJ.

Atherosclerosis. 2011 Oct;218(2):423-30. doi: 10.1016/j.atherosclerosis.2011.07.106. Epub 2011 Jul 30.

PubMed [citation]

PMID:: 21868016

See all PubMed Citations (11)

Details of each submission

From Dept. of Genetics and Pharmacogenomics, Merck Research Labs, SCV000189534.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	in vitro	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	not applicable	not applicable	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV001469531.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (11)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From GeneDx, SCV005078058.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Functional studies demonstrated that p.(P181R) is associated with altered LDLR precursor processing; however, it does not result in altered receptor activity (PMID: 21868016); Also known as p.(P160R); This variant is associated with the following publications: (PMID: 16250003, 21310417, 14508510, 20045108, 23375686, 11524740, 25487149, 22698793, 11754108, 11600564, 18279815, 25647241, 21868016, 31447099, 37409534, 35913489, 32977124)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 13, 2024

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