U.S. flag

An official website of the United States government

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

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Mar 1, 2024
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:
RCV004525832.4

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)
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:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000697237Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)
Uncertain significance
(Mar 1, 2024)
germlineclinical testing

PubMed (16)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

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

Citations

PubMed

Molecular genetics of familial hypercholesterolemia in Spain: Ten novel LDLR mutations and population analysis.

García-García AB, Real JT, Puig O, Cebolla E, Marín-García P, Martínez Ferrandis JI, García-Sogo M, Civera M, Ascaso JF, Carmena R, Armengod ME, Chaves FJ.

Hum Mutat. 2001 Nov;18(5):458-9.

PubMed [citation]
PMID:
11668640

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
See all PubMed Citations (16)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000697237.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (16)

Description

Variant summary: LDLR c.542C>G (p.Pro181Arg) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.7e-05 in 261608 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.542C>G has been reported in many FH patients/families with both co-segregation of variant with disease as well as lack of co-segregation observed (example, Garcia-Garcia_ 2001 and Garcia-Garcia _2011). In vitro functional studies showed that variant of interest altered LDLR precursor processing to the mature form, however, the protein activity was normal (Garcia-Garcia _2011) and showed comparable levels of cellular LDL-uptake to wild type (Thormaehlen_2015), suggesting a possible lack of functional effect which needs to be further clarified. The following publications have been ascertained in the context of this evaluation (PMID: 23375686, 16627557, 34297352, 25487149, 21310417, 18279815, 16250003, 21868016, 11668640, 11754108, 14508510, 20045108, 35913489, 25647241, 22698793, 31447099). ClinVar contains an entry for this variant (Variation ID: 183089). Based on the evidence outlined above, the variant was classified as uncertain significance.

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

Last Updated: Jun 29, 2024