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NM_000527.5(LDLR):c.1898G>T (p.Arg633Leu)

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Interpretation:
Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
3 (Most recent: Apr 29, 2020)
Last evaluated:
Feb 3, 2020
Accession:
VCV000252107.2
Variation ID:
252107
Description:
single nucleotide variant
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NM_000527.5(LDLR):c.1898G>T (p.Arg633Leu)

Allele ID
246403
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
19p13.2
Genomic location
19: 11120144 (GRCh38) GRCh38 UCSC
19: 11230820 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000019.10:g.11120144G>T
NC_000019.9:g.11230820G>T
NM_000527.5:c.1898G>T MANE Select NP_000518.1:p.Arg633Leu missense
... more HGVS
Protein change
R633L, R465L, R506L, R592L
Other names
-
Canonical SPDI
NC_000019.10:11120143:G:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA10585677
LDLR-LOVD, British Heart Foundation: LDLR_001074
dbSNP: rs754536745
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely pathogenic 2 criteria provided, single submitter Mar 25, 2016 RCV000237353.3
Likely pathogenic 1 criteria provided, single submitter Feb 3, 2020 RCV001174944.1
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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
(Mar 25, 2016)
criteria provided, single submitter
Method: literature only
Familial hypercholesterolemia
(Autosomal dominant inheritance)
Allele origin: germline
LDLR-LOVD, British Heart Foundation
Accession: SCV000295747.2
Submitted: (Apr 20, 2016)
Evidence details
Publications
PubMed (1)
Likely pathogenic
(Feb 03, 2020)
criteria provided, single submitter
Method: clinical testing
Familial hypercholesterolemia
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001338397.1
Submitted: (Apr 29, 2020)
Evidence details
Publications
PubMed (5)
Comment:
Variant summary: LDLR c.1898G>T (p.Arg633Leu) results in a non-conservative amino acid change located in the LDLR class B repeat (IPR000033) of the encoded protein sequence. … (more)
Pathogenic
(-)
no assertion criteria provided
Method: research
Familial hypercholesterolemia
Allele origin: germline
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum
Accession: SCV000606554.1
Submitted: (Apr 25, 2017)
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
Inheritance pattern of familial hypercholesterolemia and markers of cardiovascular risk. Kusters DM Journal of lipid research 2013 PMID: 23833242
Cardiovascular risk in relation to functionality of sequence variants in the gene coding for the low-density lipoprotein receptor: a study among 29,365 individuals tested for 64 specific low-density lipoprotein-receptor sequence variants. Huijgen R European heart journal 2012 PMID: 22390909
Molecular basis of autosomal dominant hypercholesterolemia: assessment in a large cohort of hypercholesterolemic children. van der Graaf A Circulation 2011 PMID: 21382890
Functionality of sequence variants in the genes coding for the low-density lipoprotein receptor and apolipoprotein B in individuals with inherited hypercholesterolemia. Huijgen R Human mutation 2010 PMID: 20506408
Update of the molecular basis of familial hypercholesterolemia in The Netherlands. Fouchier SW Human mutation 2005 PMID: 16250003

Text-mined citations for rs754536745...

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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 Jun 14, 2021