NM_000527.5(LDLR):c.1783C>T (p.Arg595Trp) variant is classified as Pathogenic for Familial Hypercholesterolemia by applying evidence codes (PS4, PP1_Strong, PM2, PP3 and PP4) as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1101/2021.03.17.21252755). The supporting evidence is as follows: PS4 - Variant meets PM2. Variant identified in 12 index cases. PP1_strong - 10 informative meioses identified by Laboratory of Genetics and Molecular Cardiology. PM2 - PopMax MAF = 0.00001548 (0.0015%) in European non-Finnish (gnomAD v2.1.1). PP3 - REVEL: 0,89. PP4 - Variant meets PM2. Variant identified in 12 index cases fulfilling validated clinical criteria for FH (6 cases with Simon-Broome or DLCN criteria from Ambry Genetics; 2 cases with Simon-Broome from Color laboratory; 3 cases with Simon-Broome criteria from Laboratory of Genetics and Molecular Cardiology; 1 case with Simon-Broome criteria from GeneDx).
ClinVar Genomic variation as it relates to human health
NM_000527.5(LDLR):c.1783C>T (p.Arg595Trp)
Germline
Top reviewed classifications are shown here.
Submission summary:
Reviewed by expert panel
Pathogenic
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000527.5(LDLR):c.1783C>T (p.Arg595Trp)
Variation ID: 161290 Accession: VCV000161290.38
- Type and length
-
single nucleotide variant, 1 bp
- Location
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Cytogenetic: 19p13.2 19: 11116936 (GRCh38) [ NCBI UCSC ] 19: 11227612 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Dec 7, 2014 Aug 11, 2024 Jun 9, 2021 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000527.5:c.1783C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000518.1:p.Arg595Trp missense NM_001195798.2:c.1783C>T NP_001182727.1:p.Arg595Trp missense NM_001195799.2:c.1660C>T NP_001182728.1:p.Arg554Trp missense NM_001195800.2:c.1279C>T NP_001182729.1:p.Arg427Trp missense NM_001195803.2:c.1402C>T NP_001182732.1:p.Arg468Trp missense NC_000019.10:g.11116936C>T NC_000019.9:g.11227612C>T NG_009060.1:g.32556C>T LRG_274:g.32556C>T LRG_274t1:c.1783C>T LRG_274p1:p.Arg595Trp P01130:p.Arg595Trp - Protein change
- R595W, R468W, R427W, R554W
- Other names
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NM_000527.5(LDLR):c.1783C>T
- Canonical SPDI
- NC_000019.10:11116935:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
- -
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
- -
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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| LDLR | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
4075 | 4351 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Pathogenic (15) |
reviewed by expert panel
|
Jun 9, 2021 | RCV000237585.34 | |
| Pathogenic (5) |
criteria provided, multiple submitters, no conflicts
|
Dec 1, 2023 | RCV000588105.23 | |
| Pathogenic/Likely pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
Oct 7, 2022 | RCV000518174.14 | |
| Uncertain significance (1) |
no assertion criteria provided
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Jun 1, 2014 | RCV002051683.10 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Mar 19, 2024 | RCV002399519.10 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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|---|---|---|---|---|---|
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Pathogenic
(Jun 09, 2021)
|
reviewed by expert panel
Method: curation
|
Hypercholesterolemia, familial, 1
(Semidominant inheritance)
Affected status: unknown
Allele origin:
germline
|
ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel
FDA Recognized Database
Accession: SCV001960931.1 First in ClinVar: Oct 08, 2021 Last updated: Oct 08, 2021 |
Comment:
NM_000527.5(LDLR):c.1783C>T (p.Arg595Trp) variant is classified as Pathogenic for Familial Hypercholesterolemia by applying evidence codes (PS4, PP1_Strong, PM2, PP3 and PP4) as defined by the ClinGen … (more)
NM_000527.5(LDLR):c.1783C>T (p.Arg595Trp) variant is classified as Pathogenic for Familial Hypercholesterolemia by applying evidence codes (PS4, PP1_Strong, PM2, PP3 and PP4) as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1101/2021.03.17.21252755). The supporting evidence is as follows: PS4 - Variant meets PM2. Variant identified in 12 index cases. PP1_strong - 10 informative meioses identified by Laboratory of Genetics and Molecular Cardiology. PM2 - PopMax MAF = 0.00001548 (0.0015%) in European non-Finnish (gnomAD v2.1.1). PP3 - REVEL: 0,89. PP4 - Variant meets PM2. Variant identified in 12 index cases fulfilling validated clinical criteria for FH (6 cases with Simon-Broome or DLCN criteria from Ambry Genetics; 2 cases with Simon-Broome from Color laboratory; 3 cases with Simon-Broome criteria from Laboratory of Genetics and Molecular Cardiology; 1 case with Simon-Broome criteria from GeneDx). (less)
|
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Likely pathogenic
(Dec 16, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Hypercholesterolemia, familial, 1
Affected status: yes
Allele origin:
germline
|
Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies, APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix
Accession: SCV000503414.1
First in ClinVar: Jul 29, 2016 Last updated: Jul 29, 2016 |
Comment:
subject mutated among 2600 FH index cases screened = 1 / previously described in association with FH/software prediction damaging
Number of individuals with the variant: 1
|
|
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Uncertain significance
(Mar 01, 2016)
|
criteria provided, single submitter
Method: research
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Familial hypercholesterolemia
Affected status: unknown
Allele origin:
germline
|
Fundacion Hipercolesterolemia Familiar
Study: SAFEHEART
Accession: SCV000607640.1 First in ClinVar: Sep 30, 2017 Last updated: Sep 30, 2017 |
Comment on evidence:
%MAF(ExAC):0.0008237
|
|
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Likely pathogenic
(Jun 16, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Athena Diagnostics
Accession: SCV000614004.1
First in ClinVar: Dec 19, 2017 Last updated: Dec 19, 2017 |
|
|
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Uncertain significance
(Mar 01, 2016)
|
criteria provided, single submitter
Method: research
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Familial hypercholesterolemia
Affected status: unknown
Allele origin:
germline
|
Iberoamerican FH Network
Accession: SCV000748099.1
First in ClinVar: May 19, 2018 Last updated: May 19, 2018
Comment:
Variant present in the database from Argentina
|
Comment on evidence:
%MAF(ExAC):0.0008237
|
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Uncertain significance
(Sep 07, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Hypercholesterolemia, familial, 1
Affected status: yes
Allele origin:
unknown
|
Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV001440210.2
First in ClinVar: Oct 31, 2020 Last updated: Sep 25, 2021 |
|
|
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Pathogenic
(Feb 14, 2022)
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criteria provided, single submitter
Method: clinical testing
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Familial hypercholesterolemia
Affected status: yes
Allele origin:
germline
|
DASA
Accession: SCV002097311.1
First in ClinVar: Feb 20, 2022 Last updated: Feb 20, 2022 |
Comment:
The c.1783C>T;p.(Arg595Trp) missense variant has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar: 161290; PMID: 11737238; 25461735; 27784735; 16250003; … (more)
The c.1783C>T;p.(Arg595Trp) missense variant has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar: 161290; PMID: 11737238; 25461735; 27784735; 16250003; 20538126) - PS4. The variant is located in a mutational hot spot and/or critical and well-established functional domain (Ldl_recept_b) - PM1. The variant is present at low allele frequencies population databases (rs373371572 - gnomAD 0.0002631%; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2_supporting. Pathogenic missense variant in this residue have been reported (ClinVar ID: 252029 - c.1784G>T;p.(Arg595Leu)) - PM5. The variant co-segregated with disease in multiple affected family members (PMID: 11737238; 16250003; 20538126) - PP1_strong. Multiple lines of computational evidence support a deleterious effect on the gene or gene product - PP3. In summary, the currently available evidence indicates that the variant is pathogenic. (less)
Number of individuals with the variant: 1
Sex: female
Geographic origin: Brazil
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Pathogenic
(Jul 27, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hypercholesterolemia, familial, 1
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV003827169.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
|
|
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Pathogenic
(Mar 19, 2024)
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criteria provided, single submitter
Method: clinical testing
|
Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV002710381.3
First in ClinVar: Nov 29, 2022 Last updated: Aug 11, 2024 |
Comment:
The c.1783C>T (p.R595W) alteration is located in coding exon 12 of the LDLR gene. This alteration results from a C to T substitution at nucleotide … (more)
The c.1783C>T (p.R595W) alteration is located in coding exon 12 of the LDLR gene. This alteration results from a C to T substitution at nucleotide position 1783, causing the arginine (R) at amino acid position 595 to be replaced by a tryptophan (W). Based on data from gnomAD, the T allele has an overall frequency of 0.001% (2/282862) total alleles studied. The highest observed frequency was 0.002% (2/129168) of European (non-Finnish) alleles. This variant has been reported in several individuals with familial hypercholesterolemia (FH) from varying ethnic backgrounds (Descamps, 2001; Damgaard, 2005; Tejedor, 2005; Fouchier, 2005; Chiou, 2010; Jannes, 2015; Bañares, 2017; Pirillo, 2017; Pek, 2018). Another alteration at the same codon, p.R595Q (c.1784G>A), has also been detected in individuals with FH (Fouchier, 2005). This amino acid position is highly conserved in available vertebrate species. Functional studies of this variant demonstrated reduced binding capacity and receptor recycling (Guo, 2019). This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as pathogenic. (less)
|
|
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Likely pathogenic
(Mar 25, 2016)
|
criteria provided, single submitter
Method: literature only
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Familial hypercholesterolemia
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
LDLR-LOVD, British Heart Foundation
Accession: SCV000295653.2
First in ClinVar: Jul 29, 2016 Last updated: May 19, 2018 |
Observation 1:
Number of individuals with the variant: 1
Observation 2:
Number of individuals with the variant: 1
Observation 3:
Number of individuals with the variant: 1
Observation 4:
Number of individuals with the variant: 1
Observation 5:
Number of individuals with the variant: 1
|
|
|
Pathogenic
(Mar 30, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Familial Hypercholesterolemia
Affected status: yes
Allele origin:
germline
|
U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille
Accession: SCV000494601.2
First in ClinVar: Jul 29, 2016 Last updated: Jul 21, 2017
Comment:
ACMG Guidelines: Pathogenic (ii)
|
Number of individuals with the variant: 3
Clinical Features:
Hyperbetalipoproteinemia (present) , Hypercholesterolemia (present)
Indication for testing: Familial Hypercholesterolemia
Sex: mixed
Geographic origin: France
Comment on evidence:
Dutch Lipid Clinic Scoring : Definite FH
Secondary finding: no
|
|
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Uncertain significance
(Mar 01, 2016)
|
criteria provided, single submitter
Method: research
|
Familial hypercholesterolemia
Affected status: unknown
Allele origin:
germline
|
Laboratory of Genetics and Molecular Cardiology, University of São Paulo
Study: HipercolBrasil
Accession: SCV000588606.1 First in ClinVar: Aug 13, 2017 Last updated: Aug 13, 2017 |
Comment on evidence:
%MAF(ExAC):0.0008237
|
|
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Likely pathogenic
(Dec 27, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Hypercholesterolemia, familial, 1
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
de novo
|
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München
Accession: SCV001149823.1
First in ClinVar: Feb 03, 2020 Last updated: Feb 03, 2020 |
Sex: female
Tissue: blood
|
|
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Pathogenic
(Sep 30, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Familial hypercholesterolemia
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000697210.2
First in ClinVar: Mar 17, 2018 Last updated: Jun 22, 2020 |
Comment:
Variant summary: LDLR c.1783C>T (p.Arg595Trp) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging … (more)
Variant summary: LDLR c.1783C>T (p.Arg595Trp) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251488 control chromosomes. c.1783C>T has been reported in the literature in multiple individuals affected with Familial Hypercholesterolemia in the homozygous and compound heterozygous state (Mozas_2004, Junyent_2010, Damgaard_2005, Chiou_2012, Pek_2018, Pirillo_2017). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Nine clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments, three as VUS, six as likely pathogenic/pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
|
|
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Likely pathogenic
(Mar 16, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute
Accession: SCV001433287.1
First in ClinVar: Sep 27, 2020 Last updated: Sep 27, 2020 |
|
|
|
Pathogenic
(Oct 07, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Hypercholesterolemia, familial, 1
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV002789296.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
|
|
|
Pathogenic
(Oct 07, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV002526489.3
First in ClinVar: Jun 24, 2022 Last updated: Mar 04, 2023 |
Comment:
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; … (more)
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Reported as a pathogenic variant by ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel (ClinVar Variant ID#171218; SCV001960931.1); Also known as p.(R574W); This variant is associated with the following publications: (PMID: 25637381, 28502510, 29172679, 28965616, 15823288, 16250003, 28502495, 30586733, 31491741, 31447099, 33740630, 34037665, 29353225, 32331935, 11737238, 15241806, 27578128, 30583242, 34906454, 34526433, 33994402, 34176852, 20538126, 25461735, 27784735) (less)
|
|
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Pathogenic
(Dec 01, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Familial hypercholesterolemia
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000752411.7
First in ClinVar: May 19, 2018 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 595 of the LDLR protein … (more)
This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 595 of the LDLR protein (p.Arg595Trp). This variant is present in population databases (rs373371572, gnomAD 0.002%). This missense change has been observed in individuals with familial hypercholesterolaemia (PMID: 11737238, 16250003, 20538126, 25461735, 27784735). ClinVar contains an entry for this variant (Variation ID: 161290). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt LDLR protein function with a positive predictive value of 95%. This variant disrupts the p.Arg595 amino acid residue in LDLR. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15256764, 15359125, 16250003, 18718593, 25437892, 25487149, 27497240, 28502510). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. (less)
|
|
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Pathogenic
(Apr 20, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Familial hypercholesterolemia
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000909180.4
First in ClinVar: May 20, 2019 Last updated: Feb 14, 2024 |
Comment:
This missense variant (also known as p.Arg574Trp in the mature protein) replaces arginine with tryptophan at codon 595 in the fifth LDLR type B repeat … (more)
This missense variant (also known as p.Arg574Trp in the mature protein) replaces arginine with tryptophan at codon 595 in the fifth LDLR type B repeat of the EGF precursor homology domain of the LDLR protein. Computational prediction suggests that this variant may have a deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in over 20 individuals affected with familial hypercholesterolemia (PMID: 11737238, 16250003, 20538126, 25461735, 28502510, 32044282, 32331935, 34037665, 34176852; Color internal data), including three homozygous individuals with severe phenotype (PMID: 27784735). This variant has been identified in 2/282862 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Different missense variants occurring at the same codon (p.Arg595Leu and Arg595Gln) have been reported in individuals affected with familial hypercholesterolemia (ClinVar variation ID: 252029, 183126), suggesting that arginine at this position is a functionally and clinically important residue. Based on the available evidence, this variant is classified as Pathogenic. (less)
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|
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Pathogenic
(Mar 17, 2024)
|
criteria provided, single submitter
Method: research
|
Hypercholesterolemia, familial, 1
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
Accession: SCV004804728.2
First in ClinVar: Mar 30, 2024 Last updated: Apr 06, 2024 |
|
|
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Pathogenic
(Jan 09, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Hypercholesterolemia, familial, 1
(Semidominant inheritance)
Affected status: unknown
Allele origin:
germline
|
All of Us Research Program, National Institutes of Health
Accession: SCV004822501.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
|
Comment:
This missense variant (also known as p.Arg574Trp in the mature protein) replaces arginine with tryptophan at codon 595 in the fifth LDLR type B repeat … (more)
This missense variant (also known as p.Arg574Trp in the mature protein) replaces arginine with tryptophan at codon 595 in the fifth LDLR type B repeat of the EGF precursor homology domain of the LDLR protein. Computational prediction suggests that this variant may have a deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in over 20 individuals affected with familial hypercholesterolemia (PMID: 11737238, 16250003, 20538126, 25461735, 28502510, 32044282, 32331935, 34037665, 34176852; Color internal data), including three homozygous individuals with severe phenotype (PMID: 27784735). This variant has been identified in 2/282862 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Different missense variants occurring at the same codon (p.Arg595Leu and Arg595Gln) have been reported in individuals affected with familial hypercholesterolemia (ClinVar variation ID: 252029, 183126), suggesting that arginine at this position is a functionally and clinically important residue. Based on the available evidence, this variant is classified as Pathogenic. (less)
Number of individuals with the variant: 3
|
|
|
Pathogenic
(May 12, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
familial hypercholesterolemia
Affected status: unknown
Allele origin:
unknown
|
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine
Accession: SCV005045752.1
First in ClinVar: Jun 02, 2024 Last updated: Jun 02, 2024 |
Comment:
The c.1783C>T (p.Arg595Trp) variant, also known as p.Arg574Trp in LDLR gene that encodes for low density lipoprotein receptor, has been identified in several unrelated individuals … (more)
The c.1783C>T (p.Arg595Trp) variant, also known as p.Arg574Trp in LDLR gene that encodes for low density lipoprotein receptor, has been identified in several unrelated individuals (>10) who fulfill the clinical criteria of familial hypercholesterolemia and segregated with disease in ten informative meioses (PMID:11737238, 16250003, 20538126, 25461735, 28502510). In-silico computational prediction tools suggest that the p.Arg595Trp variant may have deleterious effect on the protein function (REVEL score: 0.89). This variant is found to be rare (2/282862 chromosomes) in the general population database, gnomAD. This variant is interpreted as pathogenic by multiple submitters in the ClinVar database including the ClinGen expert panel (ClinVar ID: 161290). Another amino acid substitution at same position (p.Arg595Gln) has been classified as pathogenic by the ClinGen expert panel (ClinVar ID:183126). Therefore, the c.1783C>T (p.Arg595Trp) variant in LDLR gene is classified as pathogenic. (less)
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|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: research
|
Familial hypercholesterolemia
Affected status: unknown
Allele origin:
germline
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Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum
Accession: SCV000606512.1
First in ClinVar: Sep 30, 2017 Last updated: Sep 30, 2017 |
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Uncertain significance
(Jun 01, 2014)
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no assertion criteria provided
Method: research
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Hypercholesterolaemia
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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CSER _CC_NCGL, University of Washington
Study: ESP 6500 variant annotation
Accession: SCV000190312.1 First in ClinVar: Dec 07, 2014 Last updated: Dec 07, 2014
Comment:
Variants classified for the Actionable exomic incidental findings in 6503 participants: challenges of variant classification manuscript
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Pathogenic
(Oct 09, 2023)
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no assertion criteria provided
Method: clinical testing
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Hypercholesterolemia, familial, 1
Affected status: yes
Allele origin:
germline
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Zotz-Klimas Genetics Lab, MVZ Zotz Klimas
Accession: SCV004041644.1
First in ClinVar: Oct 14, 2023 Last updated: Oct 14, 2023 |
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Comment:
Comment:
subject mutated among 2600 FH index cases screened = 1 / previously described in association with FH/software prediction damaging
Comment:
The c.1783C>T;p.(Arg595Trp) missense variant has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar: 161290; PMID: 11737238; 25461735; 27784735; 16250003; 20538126) - PS4. The variant is located in a mutational hot spot and/or critical and well-established functional domain (Ldl_recept_b) - PM1. The variant is present at low allele frequencies population databases (rs373371572 - gnomAD 0.0002631%; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2_supporting. Pathogenic missense variant in this residue have been reported (ClinVar ID: 252029 - c.1784G>T;p.(Arg595Leu)) - PM5. The variant co-segregated with disease in multiple affected family members (PMID: 11737238; 16250003; 20538126) - PP1_strong. Multiple lines of computational evidence support a deleterious effect on the gene or gene product - PP3. In summary, the currently available evidence indicates that the variant is pathogenic.
Comment:
The c.1783C>T (p.R595W) alteration is located in coding exon 12 of the LDLR gene. This alteration results from a C to T substitution at nucleotide position 1783, causing the arginine (R) at amino acid position 595 to be replaced by a tryptophan (W). Based on data from gnomAD, the T allele has an overall frequency of 0.001% (2/282862) total alleles studied. The highest observed frequency was 0.002% (2/129168) of European (non-Finnish) alleles. This variant has been reported in several individuals with familial hypercholesterolemia (FH) from varying ethnic backgrounds (Descamps, 2001; Damgaard, 2005; Tejedor, 2005; Fouchier, 2005; Chiou, 2010; Jannes, 2015; Bañares, 2017; Pirillo, 2017; Pek, 2018). Another alteration at the same codon, p.R595Q (c.1784G>A), has also been detected in individuals with FH (Fouchier, 2005). This amino acid position is highly conserved in available vertebrate species. Functional studies of this variant demonstrated reduced binding capacity and receptor recycling (Guo, 2019). This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as pathogenic.
Comment:
Variant summary: LDLR c.1783C>T (p.Arg595Trp) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251488 control chromosomes. c.1783C>T has been reported in the literature in multiple individuals affected with Familial Hypercholesterolemia in the homozygous and compound heterozygous state (Mozas_2004, Junyent_2010, Damgaard_2005, Chiou_2012, Pek_2018, Pirillo_2017). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Nine clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments, three as VUS, six as likely pathogenic/pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Comment:
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Reported as a pathogenic variant by ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel (ClinVar Variant ID#171218; SCV001960931.1); Also known as p.(R574W); This variant is associated with the following publications: (PMID: 25637381, 28502510, 29172679, 28965616, 15823288, 16250003, 28502495, 30586733, 31491741, 31447099, 33740630, 34037665, 29353225, 32331935, 11737238, 15241806, 27578128, 30583242, 34906454, 34526433, 33994402, 34176852, 20538126, 25461735, 27784735)
Comment:
This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 595 of the LDLR protein (p.Arg595Trp). This variant is present in population databases (rs373371572, gnomAD 0.002%). This missense change has been observed in individuals with familial hypercholesterolaemia (PMID: 11737238, 16250003, 20538126, 25461735, 27784735). ClinVar contains an entry for this variant (Variation ID: 161290). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt LDLR protein function with a positive predictive value of 95%. This variant disrupts the p.Arg595 amino acid residue in LDLR. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15256764, 15359125, 16250003, 18718593, 25437892, 25487149, 27497240, 28502510). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Comment:
This missense variant (also known as p.Arg574Trp in the mature protein) replaces arginine with tryptophan at codon 595 in the fifth LDLR type B repeat of the EGF precursor homology domain of the LDLR protein. Computational prediction suggests that this variant may have a deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in over 20 individuals affected with familial hypercholesterolemia (PMID: 11737238, 16250003, 20538126, 25461735, 28502510, 32044282, 32331935, 34037665, 34176852; Color internal data), including three homozygous individuals with severe phenotype (PMID: 27784735). This variant has been identified in 2/282862 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Different missense variants occurring at the same codon (p.Arg595Leu and Arg595Gln) have been reported in individuals affected with familial hypercholesterolemia (ClinVar variation ID: 252029, 183126), suggesting that arginine at this position is a functionally and clinically important residue. Based on the available evidence, this variant is classified as Pathogenic.
Comment:
This missense variant (also known as p.Arg574Trp in the mature protein) replaces arginine with tryptophan at codon 595 in the fifth LDLR type B repeat of the EGF precursor homology domain of the LDLR protein. Computational prediction suggests that this variant may have a deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in over 20 individuals affected with familial hypercholesterolemia (PMID: 11737238, 16250003, 20538126, 25461735, 28502510, 32044282, 32331935, 34037665, 34176852; Color internal data), including three homozygous individuals with severe phenotype (PMID: 27784735). This variant has been identified in 2/282862 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Different missense variants occurring at the same codon (p.Arg595Leu and Arg595Gln) have been reported in individuals affected with familial hypercholesterolemia (ClinVar variation ID: 252029, 183126), suggesting that arginine at this position is a functionally and clinically important residue. Based on the available evidence, this variant is classified as Pathogenic.
Comment:
The c.1783C>T (p.Arg595Trp) variant, also known as p.Arg574Trp in LDLR gene that encodes for low density lipoprotein receptor, has been identified in several unrelated individuals (>10) who fulfill the clinical criteria of familial hypercholesterolemia and segregated with disease in ten informative meioses (PMID:11737238, 16250003, 20538126, 25461735, 28502510). In-silico computational prediction tools suggest that the p.Arg595Trp variant may have deleterious effect on the protein function (REVEL score: 0.89). This variant is found to be rare (2/282862 chromosomes) in the general population database, gnomAD. This variant is interpreted as pathogenic by multiple submitters in the ClinVar database including the ClinGen expert panel (ClinVar ID: 161290). Another amino acid substitution at same position (p.Arg595Gln) has been classified as pathogenic by the ClinGen expert panel (ClinVar ID:183126). Therefore, the c.1783C>T (p.Arg595Trp) variant in LDLR gene is classified as pathogenic.
Germline Functional Evidence
| 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. |
Comment:
NM_000527.5(LDLR):c.1783C>T (p.Arg595Trp) variant is classified as Pathogenic for Familial Hypercholesterolemia by applying evidence codes (PS4, PP1_Strong, PM2, PP3 and PP4) as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1101/2021.03.17.21252755). The supporting evidence is as follows: PS4 - Variant meets PM2. Variant identified in 12 index cases. PP1_strong - 10 informative meioses identified by Laboratory of Genetics and Molecular Cardiology. PM2 - PopMax MAF = 0.00001548 (0.0015%) in European non-Finnish (gnomAD v2.1.1). PP3 - REVEL: 0,89. PP4 - Variant meets PM2. Variant identified in 12 index cases fulfilling validated clinical criteria for FH (6 cases with Simon-Broome or DLCN criteria from Ambry Genetics; 2 cases with Simon-Broome from Color laboratory; 3 cases with Simon-Broome criteria from Laboratory of Genetics and Molecular Cardiology; 1 case with Simon-Broome criteria from GeneDx).
Comment:
subject mutated among 2600 FH index cases screened = 1 / previously described in association with FH/software prediction damaging
Comment:
The c.1783C>T;p.(Arg595Trp) missense variant has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar: 161290; PMID: 11737238; 25461735; 27784735; 16250003; 20538126) - PS4. The variant is located in a mutational hot spot and/or critical and well-established functional domain (Ldl_recept_b) - PM1. The variant is present at low allele frequencies population databases (rs373371572 - gnomAD 0.0002631%; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2_supporting. Pathogenic missense variant in this residue have been reported (ClinVar ID: 252029 - c.1784G>T;p.(Arg595Leu)) - PM5. The variant co-segregated with disease in multiple affected family members (PMID: 11737238; 16250003; 20538126) - PP1_strong. Multiple lines of computational evidence support a deleterious effect on the gene or gene product - PP3. In summary, the currently available evidence indicates that the variant is pathogenic.
Comment:
The c.1783C>T (p.R595W) alteration is located in coding exon 12 of the LDLR gene. This alteration results from a C to T substitution at nucleotide position 1783, causing the arginine (R) at amino acid position 595 to be replaced by a tryptophan (W). Based on data from gnomAD, the T allele has an overall frequency of 0.001% (2/282862) total alleles studied. The highest observed frequency was 0.002% (2/129168) of European (non-Finnish) alleles. This variant has been reported in several individuals with familial hypercholesterolemia (FH) from varying ethnic backgrounds (Descamps, 2001; Damgaard, 2005; Tejedor, 2005; Fouchier, 2005; Chiou, 2010; Jannes, 2015; Bañares, 2017; Pirillo, 2017; Pek, 2018). Another alteration at the same codon, p.R595Q (c.1784G>A), has also been detected in individuals with FH (Fouchier, 2005). This amino acid position is highly conserved in available vertebrate species. Functional studies of this variant demonstrated reduced binding capacity and receptor recycling (Guo, 2019). This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as pathogenic.
Comment:
Variant summary: LDLR c.1783C>T (p.Arg595Trp) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251488 control chromosomes. c.1783C>T has been reported in the literature in multiple individuals affected with Familial Hypercholesterolemia in the homozygous and compound heterozygous state (Mozas_2004, Junyent_2010, Damgaard_2005, Chiou_2012, Pek_2018, Pirillo_2017). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Nine clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments, three as VUS, six as likely pathogenic/pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Comment:
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Reported as a pathogenic variant by ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel (ClinVar Variant ID#171218; SCV001960931.1); Also known as p.(R574W); This variant is associated with the following publications: (PMID: 25637381, 28502510, 29172679, 28965616, 15823288, 16250003, 28502495, 30586733, 31491741, 31447099, 33740630, 34037665, 29353225, 32331935, 11737238, 15241806, 27578128, 30583242, 34906454, 34526433, 33994402, 34176852, 20538126, 25461735, 27784735)
Comment:
This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 595 of the LDLR protein (p.Arg595Trp). This variant is present in population databases (rs373371572, gnomAD 0.002%). This missense change has been observed in individuals with familial hypercholesterolaemia (PMID: 11737238, 16250003, 20538126, 25461735, 27784735). ClinVar contains an entry for this variant (Variation ID: 161290). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt LDLR protein function with a positive predictive value of 95%. This variant disrupts the p.Arg595 amino acid residue in LDLR. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15256764, 15359125, 16250003, 18718593, 25437892, 25487149, 27497240, 28502510). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Comment:
This missense variant (also known as p.Arg574Trp in the mature protein) replaces arginine with tryptophan at codon 595 in the fifth LDLR type B repeat of the EGF precursor homology domain of the LDLR protein. Computational prediction suggests that this variant may have a deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in over 20 individuals affected with familial hypercholesterolemia (PMID: 11737238, 16250003, 20538126, 25461735, 28502510, 32044282, 32331935, 34037665, 34176852; Color internal data), including three homozygous individuals with severe phenotype (PMID: 27784735). This variant has been identified in 2/282862 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Different missense variants occurring at the same codon (p.Arg595Leu and Arg595Gln) have been reported in individuals affected with familial hypercholesterolemia (ClinVar variation ID: 252029, 183126), suggesting that arginine at this position is a functionally and clinically important residue. Based on the available evidence, this variant is classified as Pathogenic.
Comment:
This missense variant (also known as p.Arg574Trp in the mature protein) replaces arginine with tryptophan at codon 595 in the fifth LDLR type B repeat of the EGF precursor homology domain of the LDLR protein. Computational prediction suggests that this variant may have a deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in over 20 individuals affected with familial hypercholesterolemia (PMID: 11737238, 16250003, 20538126, 25461735, 28502510, 32044282, 32331935, 34037665, 34176852; Color internal data), including three homozygous individuals with severe phenotype (PMID: 27784735). This variant has been identified in 2/282862 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Different missense variants occurring at the same codon (p.Arg595Leu and Arg595Gln) have been reported in individuals affected with familial hypercholesterolemia (ClinVar variation ID: 252029, 183126), suggesting that arginine at this position is a functionally and clinically important residue. Based on the available evidence, this variant is classified as Pathogenic.
Comment:
The c.1783C>T (p.Arg595Trp) variant, also known as p.Arg574Trp in LDLR gene that encodes for low density lipoprotein receptor, has been identified in several unrelated individuals (>10) who fulfill the clinical criteria of familial hypercholesterolemia and segregated with disease in ten informative meioses (PMID:11737238, 16250003, 20538126, 25461735, 28502510). In-silico computational prediction tools suggest that the p.Arg595Trp variant may have deleterious effect on the protein function (REVEL score: 0.89). This variant is found to be rare (2/282862 chromosomes) in the general population database, gnomAD. This variant is interpreted as pathogenic by multiple submitters in the ClinVar database including the ClinGen expert panel (ClinVar ID: 161290). Another amino acid substitution at same position (p.Arg595Gln) has been classified as pathogenic by the ClinGen expert panel (ClinVar ID:183126). Therefore, the c.1783C>T (p.Arg595Trp) variant in LDLR gene is classified as pathogenic.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Universal Screening for Familial Hypercholesterolemia in Children in Kagawa, Japan. | Matsunaga K | Journal of atherosclerosis and thrombosis | 2022 | PMID: 34176852 |
| Limited-Variant Screening vs Comprehensive Genetic Testing for Familial Hypercholesterolemia Diagnosis. | Sturm AC | JAMA cardiology | 2021 | PMID: 34037665 |
| A catalog of the pathogenic mutations of LDL receptor gene in Japanese familial hypercholesterolemia. | Tada H | Journal of clinical lipidology | 2020 | PMID: 32331935 |
| Genetic analysis of familial hypercholesterolemia in Asian Indians: A single-center study. | Setia N | Journal of clinical lipidology | 2020 | PMID: 32044282 |
| Systematic prediction of familial hypercholesterolemia caused by low-density lipoprotein receptor missense mutations. | Guo J | Atherosclerosis | 2019 | PMID: 30583242 |
| Spectrum of mutations in index patients with familial hypercholesterolemia in Singapore: Single center study. | Pek SLT | Atherosclerosis | 2018 | PMID: 29353225 |
| Spectrum of mutations in Italian patients with familial hypercholesterolemia: New results from the LIPIGEN study. | Pirillo A | Atherosclerosis. Supplements | 2017 | PMID: 28965616 |
| Preliminary spectrum of genetic variants in familial hypercholesterolemia in Argentina. | Bañares VG | Journal of clinical lipidology | 2017 | PMID: 28502510 |
| Detection of common sequence variations of familial hypercholesterolemia in Taiwan using DNA mass spectrometry. | Chiou KR | Journal of clinical lipidology | 2017 | PMID: 28502495 |
| Homozygous Familial Hypercholesterolemia in Spain: Prevalence and Phenotype-Genotype Relationship. | Sánchez-Hernández RM | Circulation. Cardiovascular genetics | 2016 | PMID: 27784735 |
| Clinical and molecular characteristics of homozygous familial hypercholesterolemia patients: Insights from SAFEHEART registry. | Alonso R | Journal of clinical lipidology | 2016 | PMID: 27578128 |
| Identification and molecular characterisation of Lausanne Institutional Biobank participants with familial hypercholesterolaemia - a proof-of-concept study. | Maurer F | Swiss medical weekly | 2016 | PMID: 27497240 |
| Actionable exomic incidental findings in 6503 participants: challenges of variant classification. | Amendola LM | Genome research | 2015 | PMID: 25637381 |
| Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction. | Do R | Nature | 2015 | PMID: 25487149 |
| Familial hypercholesterolemia in Brazil: cascade screening program, clinical and genetic aspects. | Jannes CE | Atherosclerosis | 2015 | PMID: 25461735 |
| Prevalence and clinical correlates of familial hypercholesterolemia founder mutations in the general population. | Lahtinen AM | Atherosclerosis | 2015 | PMID: 25437892 |
| Common mutations of familial hypercholesterolemia patients in Taiwan: characteristics and implications of migrations from southeast China. | Chiou KR | Gene | 2012 | PMID: 22353362 |
| Detection of mutations and large rearrangements of the low-density lipoprotein receptor gene in Taiwanese patients with familial hypercholesterolemia. | Chiou KR | The American journal of cardiology | 2010 | PMID: 20538126 |
| Impact of low-density lipoprotein receptor mutational class on carotid atherosclerosis in patients with familial hypercholesterolemia. | Junyent M | Atherosclerosis | 2010 | PMID: 19717150 |
| 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 |
| Analysis of sequence variations in the LDL receptor gene in Spain: general gene screening or search for specific alterations? | Blesa S | Clinical chemistry | 2006 | PMID: 16627557 |
| Update of the molecular basis of familial hypercholesterolemia in The Netherlands. | Fouchier SW | Human mutation | 2005 | PMID: 16250003 |
| Reliable low-density DNA array based on allele-specific probes for detection of 118 mutations causing familial hypercholesterolemia. | Tejedor D | Clinical chemistry | 2005 | PMID: 15890894 |
| The relationship of molecular genetic to clinical diagnosis of familial hypercholesterolemia in a Danish population. | Damgaard D | Atherosclerosis | 2005 | PMID: 15823288 |
| Novel and recurrent mutations of the LDL receptor gene in Korean patients with familial hypercholesterolemia. | Kim JH | Molecules and cells | 2004 | PMID: 15359125 |
| Mutations in Japanese subjects with primary hyperlipidemia--results from the Research Committee of the Ministry of Health and Welfare of Japan since 1996--. | Maruyama T | Journal of atherosclerosis and thrombosis | 2004 | PMID: 15256764 |
| Molecular characterization of familial hypercholesterolemia in Spain: identification of 39 novel and 77 recurrent mutations in LDLR. | Mozas P | Human mutation | 2004 | PMID: 15241806 |
| Impact of genetic defects on coronary atherosclerosis in patients suspected of having familial hypercholesterolaemia. | Descamps OS | European journal of clinical investigation | 2003 | PMID: 12492446 |
| Impact of genetic defects on atherosclerosis in patients suspected of familial hypercholesterolaemia. | Descamps OS | European journal of clinical investigation | 2001 | PMID: 11737238 |
| https://erepo.clinicalgenome.org/evrepo/ui/interpretation/ba5d5793-ffd3-48df-89c0-24c7600a8a6d | - | - | - | - |
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Text-mined citations for this variant ...
HelpRecord last updated Nov 03, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.