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NM_000527.5(LDLR):c.401G>T (p.Cys134Phe)

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
4 (Most recent: Jan 7, 2021)
Last evaluated:
May 29, 2020
Accession:
VCV000251204.5
Variation ID:
251204
Description:
single nucleotide variant
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NM_000527.5(LDLR):c.401G>T (p.Cys134Phe)

Allele ID
245542
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
19p13.2
Genomic location
19: 11105307 (GRCh38) GRCh38 UCSC
19: 11215983 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000019.9:g.11215983G>T
NC_000019.10:g.11105307G>T
NM_000527.5:c.401G>T MANE Select NP_000518.1:p.Cys134Phe missense
... more HGVS
Protein change
C134F, C93F
Other names
FH Alessandria
Canonical SPDI
NC_000019.10:11105306:G:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA10584903
LDLR-LOVD, British Heart Foundation: LDLR_001725
UniProtKB: P01130#VAR_062371
dbSNP: rs879254514
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, multiple submitters, no conflicts Mar 25, 2016 RCV000237376.2
Pathogenic/Likely pathogenic 2 criteria provided, multiple submitters, no conflicts May 29, 2020 RCV000775037.4
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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: SCV000294687.2
Submitted: (Apr 20, 2016)
Evidence details
Publications
PubMed (2)
Likely pathogenic
(Mar 01, 2016)
criteria provided, single submitter
Method: research
Familial hypercholesterolemia
(Autosomal dominant inheritance)
Allele origin: germline
Iberoamerican FH Network
Accession: SCV000748130.1
Submitted: (Jul 28, 2017)
Comment:
Variant present in the database from Uruguay
Evidence details
Likely pathogenic
(Mar 12, 2019)
criteria provided, single submitter
Method: clinical testing
Familial hypercholesterolemia
Allele origin: germline
Color Health, Inc
Accession: SCV000909134.2
Submitted: (May 19, 2020)
Comment:
This missense variant (also known as p.Cys113Phe in the mature protein and as FH Alessandria) is located in the third LDLR type A repeat of … (more)
Evidence details
Pathogenic
(May 29, 2020)
criteria provided, single submitter
Method: clinical testing
Familial hypercholesterolemia
Allele origin: germline
Invitae
Accession: SCV001212401.2
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (10)
Comment:
This sequence change replaces cysteine with phenylalanine at codon 134 of the LDLR protein (p.Cys134Phe). The cysteine residue is highly conserved and there is a … (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
Clinical features of bilateral temporal bone xanthoma with LDLR gene mutation. Han Y International journal of pediatric otorhinolaryngology 2015 PMID: 25921077
Spectrum of mutations and phenotypic expression in patients with autosomal dominant hypercholesterolemia identified in Italy. Bertolini S Atherosclerosis 2013 PMID: 23375686
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
Update and analysis of the University College London low density lipoprotein receptor familial hypercholesterolemia database. Leigh SE Annals of human genetics 2008 PMID: 18325082
Identification of recurrent and novel mutations in the LDL receptor gene in German patients with familial hypercholesterolemia. Nauck MS Human mutation 2001 PMID: 11462246
Clinical expression of familial hypercholesterolemia in clusters of mutations of the LDL receptor gene that cause a receptor-defective or receptor-negative phenotype. Bertolini S Arteriosclerosis, thrombosis, and vascular biology 2000 PMID: 10978268
Molecular genetic testing for familial hypercholesterolemia: spectrum of LDL receptor gene mutations in The Netherlands. Lombardi MP Clinical genetics 2000 PMID: 10735632
Three-dimensional structure of a cysteine-rich repeat from the low-density lipoprotein receptor. Daly NL Proceedings of the National Academy of Sciences of the United States of America 1995 PMID: 7603991
Disulfide bridges of a cysteine-rich repeat of the LDL receptor ligand-binding domain. Bieri S Biochemistry 1995 PMID: 7548065
Structures and functions of multiligand lipoprotein receptors: macrophage scavenger receptors and LDL receptor-related protein (LRP). Krieger M Annual review of biochemistry 1994 PMID: 7979249

Text-mined citations for rs879254514...

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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 May 10, 2021