NM_000527.4(LDLR):c.542C>G (p.Pro181Arg) AND Familial hypercholesterolemia

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Likely pathogenic(2);Uncertain significance(1) (Last evaluated: Mar 30, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
4 submissions [Details]
Record status:
current
Accession:
RCV000237262.2

Allele description

NM_000527.4(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_000527.4(LDLR):c.542C>G (p.Pro181Arg)
HGVS:
  • NC_000019.10:g.11105448C>G
  • NG_009060.1:g.21068C>G
  • NM_000527.4:c.542C>G
  • NM_001195800.1:c.314-1944C>G
  • NP_000518.1:p.Pro181Arg
  • LRG_274t1:c.542C>G
  • LRG_274:g.21068C>G
  • LRG_274p1:p.Pro181Arg
  • NC_000019.9:g.11216124C>G
  • c.542C>G
Protein change:
P181R
Links:
LDLR-LOVD, British Heart Foundation: LDLR_000361; dbSNP: rs557344672
NCBI 1000 Genomes Browser:
rs557344672
Allele Frequency:
0.00005(G)
Molecular consequence:
  • NM_001195800.1:c.314-1944C>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000527.4:c.542C>G - missense variant - [Sequence Ontology: SO:0001583]
Functional consequence:
no known functional consequence - Comment(s)
Observations:
3

Condition(s)

Name:
Familial hypercholesterolemia (FH)
Synonyms:
LDL RECEPTOR DISORDER; Hyperlipoproteinemia Type IIa; HYPER-LOW-DENSITY-LIPOPROTEINEMIA; See all synonyms [MedGen]
Identifiers:
MedGen: C0020445; Orphanet: 391665; OMIM: 143890

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
SCV000294785LDLR-LOVD, British Heart Foundationcriteria provided, single submitter
Likely pathogenic
(Mar 25, 2016)
germlineliterature only

PubMed (4)
[See all records that cite these PMIDs]

Citation Link,

SCV000503179Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies,APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foixcriteria provided, single submitter
Likely benign
(Dec 16, 2016)
germlineclinical testing

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

SCV000540742Molecular Genetics Laboratory,Centre for Cardiovascular Surgery and Transplantation

See additional submitters

criteria provided, single submitter
Uncertain significance
(Nov 5, 2016)
unknownclinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV000583701U4M - Lille University & CHRU Lille,Université Lille 2 - CHRU de Lillecriteria provided, single submitter
Likely pathogenic
(Mar 30, 2017)
germlineclinical testing

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

Description

ACMG Guidelines: Likely Pathogenic (ii)

SCV000583701

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes61not provided2604not providedclinical testing, literature only
Caucasianunknownyes22not provided3964yesclinical testing

Citations

PubMed

Update of the molecular basis of familial hypercholesterolemia in The Netherlands.

Fouchier SW, Kastelein JJ, Defesche JC.

Hum Mutat. 2005 Dec;26(6):550-6.

PubMed [citation]
PMID:
16250003
See all PubMed Citations (6)

Details of each submission

From LDLR-LOVD, British Heart Foundation, SCV000294785.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedliterature only PubMed (4)
2not provided1not providednot providedliterature only PubMed (4)
3not provided1not providednot providedliterature only PubMed (4)
4not provided1not providednot providedliterature only PubMed (4)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyes1not providednot provided1not providednot providednot provided
2germlineyes1not providednot provided1not providednot providednot provided
3germlineyes1not providednot provided1not providednot providednot provided
4germlineyes1not providednot provided1not providednot providednot provided

From Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies,APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix, SCV000503179.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

subject mutated among 2600 FH index cases screened = 1 / Software predictions: Conflicting

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyes2600not providednot provided1not providednot providednot provided

From Molecular Genetics Laboratory,Centre for Cardiovascular Surgery and Transplantation, SCV000540742.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1Caucasian2not providedyesclinical testing PubMed (3)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownyes3964Whole bloodnot provided2not provided2not provided

From U4M - Lille University & CHRU Lille,Université Lille 2 - CHRU de Lille, SCV000583701.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

Dutch Lipid Clinic Scoring : Probable FH

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not provided1not provided

Last Updated: Sep 5, 2017