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NM_000527.5(LDLR):c.292G>A (p.Gly98Ser)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely pathogenic(1);Uncertain significance(2)

Review status:
criteria provided, conflicting interpretations
Submissions:
4 (Most recent: Aug 31, 2021)
Last evaluated:
Feb 19, 2021
Accession:
VCV000251118.6
Variation ID:
251118
Description:
single nucleotide variant
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NM_000527.5(LDLR):c.292G>A (p.Gly98Ser)

Allele ID
245461
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
19p13.2
Genomic location
19: 11102765 (GRCh38) GRCh38 UCSC
19: 11213441 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NM_000527.4:c.292G>A NP_000518.1:p.Gly98Ser missense
NC_000019.10:g.11102765G>A
NC_000019.9:g.11213441G>A
... more HGVS
Protein change
G98S
Other names
-
Canonical SPDI
NC_000019.10:11102764:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
Exome Aggregation Consortium (ExAC) 0.00006
The Genome Aggregation Database (gnomAD) 0.00003
The Genome Aggregation Database (gnomAD), exomes 0.00004
Trans-Omics for Precision Medicine (TOPMed) 0.00005
Links
ClinGen: CA042749
LDLR-LOVD, British Heart Foundation: LDLR_001032
dbSNP: rs750474121
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 RCV000238329.3
Uncertain significance 1 criteria provided, single submitter Feb 19, 2021 RCV001177872.2
Uncertain significance 1 criteria provided, single submitter Jun 18, 2019 RCV001582801.3
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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
3091 3291

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: SCV000294583.2
Submitted: (Apr 20, 2016)
Evidence details
Publications
PubMed (1)
Uncertain significance
(Feb 19, 2021)
criteria provided, single submitter
Method: clinical testing
Familial hypercholesterolemia
Allele origin: germline
Color Health, Inc
Accession: SCV001342163.2
Submitted: (Jun 11, 2021)
Evidence details
Comment:
This missense variant (also known as p.Gly77Ser in the mature protein) replaces glycine with serine at codon 98 of the LDLR protein. Computational prediction suggests … (more)
Uncertain significance
(Jun 18, 2019)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV001812175.1
Submitted: (Aug 31, 2021)
Evidence details
Comment:
In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 32041611, 30971288, … (more)
Pathogenic
(-)
no assertion criteria provided
Method: research
Familial hypercholesterolemia
Allele origin: germline
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum
Accession: SCV000606065.1
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
Update of the molecular basis of familial hypercholesterolemia in The Netherlands. Fouchier SW Human mutation 2005 PMID: 16250003

Text-mined citations for rs750474121...

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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 Nov 06, 2021