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NM_000527.5(LDLR):c.1586+5G>C

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely pathogenic(3);Uncertain significance(1)

Review status:
criteria provided, conflicting interpretations
Submissions:
7 (Most recent: May 26, 2021)
Last evaluated:
Jun 1, 2019
Accession:
VCV000440652.5
Variation ID:
440652
Description:
single nucleotide variant
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NM_000527.5(LDLR):c.1586+5G>C

Allele ID
434303
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
19p13.2
Genomic location
19: 11113767 (GRCh38) GRCh38 UCSC
19: 11224443 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NM_000527.4(LDLR):c.1586+5G>C
NC_000019.10:g.11113767G>C
NC_000019.9:g.11224443G>C
... more HGVS
Protein change
-
Other names
-
Canonical SPDI
NC_000019.10:11113766:G:C
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA632115377
dbSNP: rs781362878
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely pathogenic 3 criteria provided, single submitter Apr 6, 2016 RCV000586202.3
Likely pathogenic 1 criteria provided, single submitter Jun 1, 2019 RCV001509011.1
Conflicting interpretations of pathogenicity 3 criteria provided, conflicting interpretations Mar 10, 2019 RCV000508837.4
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
LDLR Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
3089 3289

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(May 30, 2017)
criteria provided, single submitter
Method: clinical testing
Familial hypercholesterolemia
Allele origin: germline
Invitae
Accession: SCV000627020.1
Submitted: (Oct 05, 2017)
Evidence details
Comment:
This sequence change falls in intron 10 of the LDLR gene. It does not directly change the encoded amino acid sequence of the LDLR protein, … (more)
Likely pathogenic
(Apr 06, 2016)
criteria provided, single submitter
Method: clinical testing
Familial hypercholesterolemia
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000697203.1
Submitted: (Jan 25, 2018)
Evidence details
Publications
PubMed (2)
Comment:
Variant summary: c.1586+5G>C affects a conserved nucleotide, resulting in an intronic change. Mutation taster predicts this variant to be disease-causing. 5/5 programs in Alamut predict … (more)
Uncertain significance
(Mar 10, 2019)
criteria provided, single submitter
Method: research
Familial hypercholesterolemia 1
Allele origin: germline
Brunham Lab, Centre for Heart and Lung Innovation,University of British Columbia
Accession: SCV001432659.1
Submitted: (Sep 16, 2020)
Evidence details
Likely pathogenic
(Jun 01, 2019)
criteria provided, single submitter
Method: clinical testing
Not provided
Allele origin: germline
Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV001715492.1
Submitted: (May 26, 2021)
Evidence details
Publications
PubMed (1)
Comment:
PM1, PS4_moderate, PP1, PP3
Pathogenic
(-)
no assertion criteria provided
Method: research
Familial hypercholesterolemia
Allele origin: germline
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum
Accession: SCV000606462.1
Submitted: (Apr 25, 2017)
Evidence details
Uncertain significance
(Jan 22, 2020)
no assertion criteria provided
Method: curation
Familial hypercholesterolemia
(Autosomal dominant inheritance)
Allele origin: germline
Broad Institute Rare Disease Group, Broad Institute
Accession: SCV001422708.1
Submitted: (Mar 09, 2020)
Evidence details
Publications
PubMed (1)
Other databases
https://erepo.clinicalgenome.org…
Comment:
The c.1586+5G>C variant in LDLR has been reported in at least 2 Taiwanese individuals with familial hypercholesterolemia (PMID: 17964958), and has been identified in 0.02% … (more)
Likely pathogenic
(Sep 16, 2020)
no assertion criteria provided
Method: clinical testing
Familial hypercholesterolemia
Allele origin: germline
Natera, Inc.
Accession: SCV001460279.1
Submitted: (Dec 28, 2020)
Evidence details

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Risk of Premature Atherosclerotic Disease in Patients With Monogenic Versus Polygenic Familial Hypercholesterolemia. Trinder M Journal of the American College of Cardiology 2019 PMID: 31345425
The use of next-generation sequencing in clinical diagnosis of familial hypercholesterolemia. Vandrovcova J Genetics in medicine : official journal of the American College of Medical Genetics 2013 PMID: 23680767
LDLR and ApoB are major genetic causes of autosomal dominant hypercholesterolemia in a Taiwanese population. Yang KC Journal of the Formosan Medical Association = Taiwan yi zhi 2007 PMID: 17964958
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/d78133e9-4512-4ec7-b878-d73cac005f01 - - - -

Text-mined citations for rs781362878...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Oct 24, 2021