NM_000527.5(LDLR):c.1837G>A (p.Val613Ile) AND Familial hypercholesterolemia 1

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(2);Uncertain significance(2) (Last evaluated: May 18, 2021)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
5 submissions [Details]
Record status:
current
Accession:
RCV000210230.7

Allele description [Variation Report for NM_000527.5(LDLR):c.1837G>A (p.Val613Ile)]

NM_000527.5(LDLR):c.1837G>A (p.Val613Ile)

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.1837G>A (p.Val613Ile)
HGVS:
  • NC_000019.10:g.11116990G>A
  • NG_009060.1:g.32610G>A
  • NM_000527.4:c.1837G>A
  • NM_000527.5:c.1837G>AMANE SELECT
  • NM_001195798.2:c.1837G>A
  • NM_001195799.2:c.1714G>A
  • NM_001195800.2:c.1333G>A
  • NM_001195803.2:c.1456G>A
  • NP_000518.1:p.Val613Ile
  • NP_000518.1:p.Val613Ile
  • NP_001182727.1:p.Val613Ile
  • NP_001182728.1:p.Val572Ile
  • NP_001182729.1:p.Val445Ile
  • NP_001182732.1:p.Val486Ile
  • LRG_274t1:c.1837G>A
  • LRG_274:g.32610G>A
  • LRG_274p1:p.Val613Ile
  • NC_000019.9:g.11227666G>A
  • c.1837G>A
Protein change:
V445I
Links:
LDLR-LOVD, British Heart Foundation: LDLR_000250;
Molecular consequence:
  • NM_000527.4:c.1837G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000527.5:c.1837G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.1837G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195799.2:c.1714G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195800.2:c.1333G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195803.2:c.1456G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Familial hypercholesterolemia 1 (FHCL1)
Synonyms:
LDL RECEPTOR DISORDER; Hyperlipoproteinemia Type IIa; HYPER-LOW-DENSITY-LIPOPROTEINEMIA; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0007750; MedGen: C0745103; 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
SCV000266314Cardiovascular Biomarker Research Laboratory,Mayo Clinic - RIGHTcriteria provided, single submitter
Likely benign
(Aug 31, 2015)
germlineresearch

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

Kullo Lab Assertion Criteria_01072016.pdf,

Citation Link,

SCV000295691LDLR-LOVD, British Heart Foundationcriteria provided, single submitter
Likely benign
(Mar 25, 2016)
germlineliterature only

PubMed (2)
[See all records that cite these PMIDs]

Citation Link,

SCV000588610Laboratory of Genetics and Molecular Cardiology, University of São Paulo - HipercolBrasilcriteria provided, single submitter
Uncertain significance
(Mar 1, 2016)
germlineresearch

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

SCV000606532Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrumno assertion criteria providedPathogenicgermlineresearch

SCV001653367Nilou-Genome Labcriteria provided, single submitter
Uncertain significance
(May 18, 2021)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes2not providednot provided2not providedliterature only
not providedgermlinenonot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedresearch
Whitegermlinenonot providednot providednot provided1013not providedresearch

Citations

PubMed

Variability in assigning pathogenicity to incidental findings: insights from LDLR sequence linked to the electronic health record in 1013 individuals.

Safarova MS, Klee EW, Baudhuin LM, Winkler EM, Kluge ML, Bielinski SJ, Olson JE, Kullo IJ.

Eur J Hum Genet. 2017 Apr;25(4):410-415. doi: 10.1038/ejhg.2016.193. Epub 2017 Feb 1.

PubMed [citation]
PMID:
28145427
PMCID:
PMC5386413

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 (4)

Details of each submission

From Cardiovascular Biomarker Research Laboratory,Mayo Clinic - RIGHT, SCV000266314.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1Whitenot providednot providednot providedresearch PubMed (1)

Description

MAF =<0.3%

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineno1013not providedassert pathogenicitynot providednot providednot providednot provided

From LDLR-LOVD, British Heart Foundation, SCV000295691.2

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

From Laboratory of Genetics and Molecular Cardiology, University of São Paulo - HipercolBrasil, SCV000588610.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedresearch PubMed (1)

Description

%MAF(ExAC):0.001648

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

From Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum, SCV000606532.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedresearchnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Nilou-Genome Lab, SCV001653367.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenonot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 8, 2021

Support Center