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NM_000527.5(LDLR):c.1745T>C (p.Leu582Pro)

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Interpretation:
Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
7 (Most recent: Jan 7, 2021)
Last evaluated:
Jan 23, 2020
Accession:
VCV000226372.8
Variation ID:
226372
Description:
single nucleotide variant
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NM_000527.5(LDLR):c.1745T>C (p.Leu582Pro)

Allele ID
228184
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
19p13.2
Genomic location
19: 11116898 (GRCh38) GRCh38 UCSC
19: 11227574 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000019.10:g.11116898T>C
NC_000019.9:g.11227574T>C
NG_009060.1:g.32518T>C
... more HGVS
Protein change
L582P, L541P, L414P, L455P
Other names
NP_000518.1:p.L582P
Canonical SPDI
NC_000019.10:11116897:T:C
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA10576318
LDLR-LOVD, British Heart Foundation: LDLR_000980
dbSNP: rs875989930
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely pathogenic 4 criteria provided, multiple submitters, no conflicts Dec 16, 2016 RCV000211698.6
Likely pathogenic 3 criteria provided, multiple submitters, no conflicts Jan 23, 2020 RCV000775075.6
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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
3093 3293

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(Mar 25, 2016)
criteria provided, single submitter
Method: literature only
Familial hypercholesterolemia
(Autosomal dominant inheritance)
Allele origin: germline
LDLR-LOVD, British Heart Foundation
Accession: SCV000295631.2
Submitted: (Apr 20, 2016)
Evidence details
Publications
PubMed (2)
Likely pathogenic
(-)
criteria provided, single submitter
Method: clinical testing
Familial hypercholesterolemia 1
(Autosomal dominant inheritance)
Allele origin: germline
Robarts Research Institute,Western University
Accession: SCV000484721.1
Submitted: (Nov 23, 2016)
Evidence details
Likely pathogenic
(Dec 16, 2016)
criteria provided, single submitter
Method: clinical testing
Familial hypercholesterolemia 1
Allele origin: germline
Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies,APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix
Accession: SCV000503406.1
Submitted: (Jan 23, 2017)
Evidence details
Comment:
subject mutated among 2600 FH index cases screened = 1/software prediction damaging
Likely pathogenic
(Mar 22, 2019)
criteria provided, single submitter
Method: clinical testing
Familial hypercholesterolemia
Allele origin: germline
Color Health, Inc
Accession: SCV000909177.2
Submitted: (May 19, 2020)
Comment:
This missense variant (also known as p.Leu561Pro in the mature protein) is located in the fifth LDLR type B repeat of the EGF precursor homology … (more)
Evidence details
Likely pathogenic
(Jan 23, 2020)
criteria provided, single submitter
Method: clinical testing
Familial hypercholesterolemia
Allele origin: germline
Invitae
Accession: SCV000957611.3
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (3)
Comment:
This sequence change replaces leucine with proline at codon 582 of the LDLR protein (p.Leu582Pro). The leucine residue is highly conserved and there is a … (more)
Pathogenic
(Aug 07, 2012)
no assertion criteria provided
Method: clinical testing
Familial hypercholesterolemia
Allele origin: germline
Cardiovascular Genetics Laboratory,PathWest Laboratory Medicine WA - Fiona Stanley Hospital
Accession: SCV000268635.1
Submitted: (May 09, 2016)
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: SCV001422865.1
Submitted: (Mar 09, 2020)
Evidence details
Publications
PubMed (3)
Other databases
https://erepo.clinicalgenome.org…
Comment:
The p.Leu582Pro variant in LDLR has been reported in 4 European individuals with familial hypercholesterolemia (PMID: 28161202, 15199436, 11668627), and was absent from large population … (more)

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
Analysis of Children and Adolescents with Familial Hypercholesterolemia. Minicocci I The Journal of pediatrics 2017 PMID: 28161202
Polygenic Versus Monogenic Causes of Hypercholesterolemia Ascertained Clinically. Wang J Arteriosclerosis, thrombosis, and vascular biology 2016 PMID: 27765764
Application of molecular genetics for diagnosing familial hypercholesterolemia in Norway: results from a family-based screening program. Leren TP Seminars in vascular medicine 2004 PMID: 15199436
Low density lipoprotein receptor (LDLR) gene mutations in Canadian subjects with familial hypercholesterolemia, but not of French descent. Wang J Human mutation 2001 PMID: 11668627
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/d3d04606-333e-47a2-94f4-65226e2563ae - - - -

Text-mined citations for rs875989930...

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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 21, 2021