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NM_000527.5(LDLR):c.1049G>C (p.Arg350Pro)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely pathogenic(2);Uncertain significance(1)

Review status:
criteria provided, conflicting interpretations
Submissions:
4 (Most recent: Jun 11, 2021)
Last evaluated:
Nov 17, 2020
Accession:
VCV000226343.4
Variation ID:
226343
Description:
single nucleotide variant
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NM_000527.5(LDLR):c.1049G>C (p.Arg350Pro)

Allele ID
228157
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
19p13.2
Genomic location
19: 11110760 (GRCh38) GRCh38 UCSC
19: 11221436 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000019.10:g.11110760G>C
NC_000019.9:g.11221436G>C
NM_000527.5:c.1049G>C MANE Select NP_000518.1:p.Arg350Pro missense
... more HGVS
Protein change
R350P, R223P, R182P, R309P
Other names
FH Alghero
Canonical SPDI
NC_000019.10:11110759:G:C
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
Trans-Omics for Precision Medicine (TOPMed) 0.00001
Links
ClinGen: CA10576296
LDLR-LOVD, British Heart Foundation: LDLR_001337
UniProtKB: P01130#VAR_005368
dbSNP: rs875989914
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely pathogenic 1 criteria provided, single submitter Nov 17, 2020 RCV001183695.2
Conflicting interpretations of pathogenicity 3 criteria provided, conflicting interpretations Mar 3, 2017 RCV000211597.4
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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
3087 3287

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: SCV000295162.2
Submitted: (Apr 20, 2016)
Evidence details
Publications
PubMed (1)
Uncertain significance
(Mar 03, 2017)
criteria provided, single submitter
Method: clinical testing
Familial hypercholesterolemia
Allele origin: germline
Invitae
Accession: SCV000627011.1
Submitted: (Oct 05, 2017)
Evidence details
Comment:
This sequence change replaces arginine with proline at codon 350 of the LDLR protein (p.Arg350Pro). The arginine residue is moderately conserved and there is a … (more)
Likely pathogenic
(Nov 17, 2020)
criteria provided, single submitter
Method: clinical testing
Familial hypercholesterolemia
Allele origin: germline
Color Health, Inc
Accession: SCV001349491.2
Submitted: (Jun 11, 2021)
Evidence details
Comment:
This missense variant (also known as p.Arg329Pro in the mature protein) replaces arginine with proline at codon 350 in the EGF-like repeat A of the … (more)
Pathogenic
(Jun 05, 2008)
no assertion criteria provided
Method: clinical testing
Familial hypercholesterolemia
Allele origin: germline
Cardiovascular Genetics Laboratory,PathWest Laboratory Medicine WA - Fiona Stanley Hospital
Accession: SCV000268596.1
Submitted: (May 09, 2016)
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
Characterization of mutations in the low density lipoprotein (LDL)-receptor gene in patients with homozygous familial hypercholesterolemia, and frequency of these mutations in FH patients in the United Kingdom. Webb JC Journal of lipid research 1996 PMID: 9026534

Text-mined citations for rs875989914...

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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 19, 2021