Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation

ClinVar Genomic variation as it relates to human health

Advanced search

NM_000527.5(LDLR):c.1252G>A (p.Glu418Lys)

Help
Interpretation:
Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
8 (Most recent: Nov 19, 2021)
Last evaluated:
May 27, 2020
Accession:
VCV000225182.6
Variation ID:
225182
Description:
single nucleotide variant
Help

NM_000527.5(LDLR):c.1252G>A (p.Glu418Lys)

Allele ID
227097
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
19p13.2
Genomic location
19: 11113343 (GRCh38) GRCh38 UCSC
19: 11224019 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
LRG_274t1:c.1252G>A
LRG_274:g.28963G>A
NC_000019.10:g.11113343G>A
... more HGVS
Protein change
E418K, E250K, E377K, E291K
Other names
-
Canonical SPDI
NC_000019.10:11113342:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA358781
LDLR-LOVD, British Heart Foundation: LDLR_000942
VarSome
Help

Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely pathogenic 6 criteria provided, multiple submitters, no conflicts Nov 5, 2016 RCV000210833.6
Likely pathogenic 2 criteria provided, single submitter May 27, 2020 RCV001181607.3
Help
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

Help
Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(Apr 03, 2016)
criteria provided, single submitter
Method: literature only
Familial hypercholesterolemia 1
Allele origin: germline
SNPedia
Accession: SCV000267119.1
Submitted: (Apr 07, 2016)
Evidence details
Publications
PubMed (1)
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: SCV000295328.2
Submitted: (Apr 20, 2016)
Evidence details
Publications
PubMed (1)
Likely pathogenic
(Nov 05, 2016)
criteria provided, single submitter
Method: clinical testing
Familial hypercholesterolemia 1
(Autosomal dominant inheritance)
Allele origin: unknown
Molecular Genetics Laboratory,Centre for Cardiovascular Surgery and Transplantation
Additional submitter:
Centre of Molecular Biology and Gene Therapy,University Hospital Brno
Accession: SCV000540807.1
Submitted: (Mar 30, 2017)
Evidence details
Likely pathogenic
(Mar 01, 2016)
criteria provided, single submitter
Method: research
Familial hypercholesterolemia
(Autosomal dominant inheritance)
Allele origin: germline
Laboratory of Genetics and Molecular Cardiology, University of São Paulo
Study: HipercolBrasil
Accession: SCV000588569.1
Submitted: (Aug 04, 2017)
Evidence details
Likely pathogenic
(Mar 01, 2016)
criteria provided, single submitter
Method: research
Familial hypercholesterolemia
(Autosomal dominant inheritance)
Allele origin: germline
Iberoamerican FH Network
Accession: SCV000748144.1
Submitted: (Jul 28, 2017)
Comment:
Variant present in the database from Uruguay
Evidence details
Likely pathogenic
(May 27, 2020)
criteria provided, single submitter
Method: clinical testing
Familial hypercholesterolemia
Allele origin: germline
Color Health, Inc
Accession: SCV001346786.2
Submitted: (Jun 11, 2021)
Evidence details
Comment:
This missense variant (also known as p.Glu397Lys in the mature protein) is located in the LDLR type B repeat 1 of the EGF precursor homology … (more)
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: SCV001422750.1
Submitted: (Mar 09, 2020)
Evidence details
Publications
PubMed (2)
Other databases
https://erepo.clinicalgenome.org…
Comment:
The p.Glu418Lys variant in LDLR has been reported in 2 individuals (1 Japanese) with familial hypercholesterolemia (PMID: 27050191, 12417285), and has been identified in 0.0009% … (more)
Likely pathogenic
(Dec 19, 2019)
no assertion criteria provided
Method: clinical testing
Familial hypercholesterolemia 1
Allele origin: germline
PerkinElmer Genomics
Accession: SCV002022660.1
Submitted: (Nov 19, 2021)
Evidence details

Functional evidence

Help
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

Help
Title Author Journal Year Link
Diagnostic Yield and Clinical Utility of Sequencing Familial Hypercholesterolemia Genes in Patients With Severe Hypercholesterolemia. Khera AV Journal of the American College of Cardiology 2016 PMID: 27050191
Update of Japanese common LDLR gene mutations and their phenotypes: Mild type mutation L547V might predominate in the Japanese population. Miyake Y Atherosclerosis 2009 PMID: 18718593
Molecular genetic analysis of familial hypercholesterolemia: spectrum and regional difference of LDL receptor gene mutations in Japanese population. Yu W Atherosclerosis 2002 PMID: 12417285
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/7c2381f2-f4e1-44e1-9481-3054b1e2c394 - - - -

Record last updated Dec 04, 2021