ClinVar Genomic variation as it relates to human health
NM_000527.5(LDLR):c.1238C>T (p.Thr413Met)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000527.5(LDLR):c.1238C>T (p.Thr413Met)
Variation ID: 161276 Accession: VCV000161276.37
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 19p13.2 19: 11113329 (GRCh38) [ NCBI UCSC ] 19: 11224005 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Sep 16, 2024 Jun 9, 2021 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000527.5:c.1238C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000518.1:p.Thr413Met missense NM_001195798.2:c.1238C>T NP_001182727.1:p.Thr413Met missense NM_001195799.2:c.1115C>T NP_001182728.1:p.Thr372Met missense NM_001195800.2:c.734C>T NP_001182729.1:p.Thr245Met missense NM_001195803.2:c.857C>T NP_001182732.1:p.Thr286Met missense NC_000019.10:g.11113329C>T NC_000019.9:g.11224005C>T NG_009060.1:g.28949C>T LRG_274:g.28949C>T LRG_274t1:c.1238C>T LRG_274p1:p.Thr413Met - Protein change
- T413M, T286M, T372M, T245M
- Other names
- NM_000527.5(LDLR):c.1238C>T
- Canonical SPDI
- NC_000019.10:11113328: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.
The Genome Aggregation Database (gnomAD) 0.00001
Exome Aggregation Consortium (ExAC) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00003
Trans-Omics for Precision Medicine (TOPMed) 0.00003
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
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 | ||
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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 |
4073 | 4349 |
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. |
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Likely pathogenic (11) |
reviewed by expert panel
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Jun 9, 2021 | RCV000211581.25 | |
Likely pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Feb 18, 2024 | RCV000519267.15 | |
Pathogenic/Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Jan 23, 2024 | RCV000775060.22 | |
Uncertain significance (1) |
no assertion criteria provided
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Jun 1, 2014 | RCV002051669.10 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Feb 1, 2023 | RCV002362782.11 |
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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Likely pathogenic
(Jun 09, 2021)
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reviewed by expert panel
Method: curation
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Hypercholesterolemia, familial, 1
(Semidominant inheritance)
Affected status: unknown
Allele origin:
germline
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ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel
FDA Recognized Database
Accession: SCV001960926.1 First in ClinVar: Oct 08, 2021 Last updated: Oct 08, 2021 |
Comment:
NM_000527.5(LDLR):c.1238C>T (p.Thr413Met) variant is classified as Likely pathogenic for Familial Hypercholesterolemia by applying evidence codes (PM2, PS4_Moderate, PP1 and PP4) as defined by the ClinGen … (more)
NM_000527.5(LDLR):c.1238C>T (p.Thr413Met) variant is classified as Likely pathogenic for Familial Hypercholesterolemia by applying evidence codes (PM2, PS4_Moderate, PP1 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: PM2 - PopMax MAF = 0.00006533 (0.007%) in South Asian (gnomAD v2.1.1). PS4_moderate - Variant meets PM2. Variant identified in 6 index cases. PP1 - Variant segregates with phenotype in 2 members of family (2 meiosis) from GeneDx laboratory. PP4 - Variant meets PM2. Variant identified in 6 index cases (2 cases from Center of molecular biology and gene therapy with Simon-Broome criteria; 1 case from GeneDx laboratory with Simon Broome criteria, 1 case from Color laboratory with DLCN criteria, 2 cases from Cardiovascular Genetics Laboratory (PathWest Laboratory Medicine WA) with DLCN criteria). (less)
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Uncertain significance
(Aug 31, 2015)
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criteria provided, single submitter
Method: research
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Hypercholesterolemia, familial, 1
Moderate hypercholesterolemia
Affected status: no
Allele origin:
germline
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Cardiovascular Biomarker Research Laboratory, Mayo Clinic
Study: RIGHT
Accession: SCV000266311.2 First in ClinVar: Mar 24, 2016 Last updated: Jul 29, 2016 |
Comment:
MAF =<0.3%, likely pathogenic based on the integrative in-silico score, previously reported as P/LP in the literature
Indication for testing: Familial hypercholesterolemia
Age: 50-59 years
Sex: female
Ethnicity/Population group: White
Geographic origin: United States
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Likely pathogenic
(Dec 23, 2021)
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criteria provided, single submitter
Method: clinical testing
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Hypercholesterolemia, familial, 1
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002813855.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Likely pathogenic
(Oct 17, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV004562712.1
First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024 |
Comment:
The LDLR c.1238C>T; p.Thr413Met variant (rs368562025) is reported in the literature in multiple individuals affected with familial hypercholesterolemia and myocardial infarction (Do 2015, Dong 2022, … (more)
The LDLR c.1238C>T; p.Thr413Met variant (rs368562025) is reported in the literature in multiple individuals affected with familial hypercholesterolemia and myocardial infarction (Do 2015, Dong 2022, eMERGE Consortium 2019, Sturm 2021, Sustar 2022). This variant is also reported as likely pathogenic by an expert panel in ClinVar (Variation ID: 161276). This variant is found in the general population with an overall allele frequency of 0.003% (7/251176 alleles) in the Genome Aggregation Database. Computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.692). Based on available information, this variant is considered to be likely pathogenic. References: Do R, et al. Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction. Nature. 2015 Feb 5;518(7537):102-6. PMID: 25487149. Dong W et al. Whole-exome sequencing reveals damaging gene variants associated with hypoalphalipoproteinemia. J Lipid Res. 2022 Jun;63(6):100209. PMID: 35460704. eMERGE Consortium et al. Harmonizing Clinical Sequencing and Interpretation for the eMERGE III Network. Am J Hum Genet. 2019 Sep 5;105(3):588-605. PMID: 31447099. Sturm AC et al. Limited-Variant Screening vs Comprehensive Genetic Testing for Familial Hypercholesterolemia Diagnosis. JAMA Cardiol. 2021 Aug 1;6(8):902-909. PMID: 34037665. Sustar U et al. Universal screening for familial hypercholesterolemia in 2 populations. Genet Med. 2022 Oct;24(10):2103-2111. PMID: 35913489. (less)
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Likely Pathogenic
(Jul 07, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hypercholesterolemia, familial, 1
(Semidominant inheritance)
Affected status: unknown
Allele origin:
germline
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All of Us Research Program, National Institutes of Health
Accession: SCV004820282.1
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)
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Comment:
This missense variant replaces threonine with methionine at codon 413 in the LDLR type B repeat 1 of the EGF precursor homology domain of the … (more)
This missense variant replaces threonine with methionine at codon 413 in the LDLR type B repeat 1 of the EGF precursor homology domain of the LDLR protein. This variant is also known as p.Thr392Met in the mature protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Functional studies have indicated no significant change in LDLR protein expression and function due to this variant (PMID: 32015373, 34029164). This variant has been reported in over twenty heterozygous individuals affected with familial hypercholesterolemia (PMID: 11668627, 11857755, 15015036, 15199436, 15576851, 17539906, 19843101, 22883975, 25682026, 31993549; ClinVar SCV001960926.1) and in an individual affected with myocardial infarction (PMID: 25487149). This variant has been observed in an individual with severe familial hypercholesterolemia who also carried a pathogenic truncation variant in the same gene (PMID: 34029164). This variant has been reported to segregate with disease in two members of a family (ClinVar SCV001960926.1). This variant has been identified in 7/251176 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Likely Pathogenic. (less)
Number of individuals with the variant: 3
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Likely pathogenic
(Feb 18, 2024)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000617508.5
First in ClinVar: Dec 19, 2017 Last updated: Sep 16, 2024 |
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; This variant is associated with the following publications: (PMID: 24055113, 25487149, 11668627, 11857755, 25637381, 15015036, 15576851, 15199436, 17539906, 28145427, 32015373, 32719484, 32522009, 30586733, 31447099, 34037665, 25682026, 27783906, 22883975, 35913489, 33854068, 34906840, Gratton2023[CaseReport], 37409534, 37443404, 35460704) (less)
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Likely pathogenic
(Mar 25, 2016)
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criteria provided, single submitter
Method: literature only
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Familial hypercholesterolemia
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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LDLR-LOVD, British Heart Foundation
Accession: SCV000295318.2
First in ClinVar: Jul 29, 2016 Last updated: Sep 30, 2017 |
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
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Uncertain significance
(Dec 16, 2016)
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criteria provided, single submitter
Method: clinical testing
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Hypercholesterolemia, familial, 1
Affected status: yes
Allele origin:
germline
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Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies, APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix
Accession: SCV000503321.1
First in ClinVar: Jul 29, 2016 Last updated: Jul 29, 2016 |
Comment:
subject mutated among 2600 FH index cases screened = 1 / Software predictions: Conflicting
Number of individuals with the variant: 1
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Likely pathogenic
(Jan 03, 2017)
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criteria provided, single submitter
Method: clinical testing
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Hypercholesterolemia, familial, 1
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
unknown
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Molecular Genetics Laboratory, Centre for Cardiovascular Surgery and Transplantation
Additional submitter:
Centre of Molecular Biology and Gene Therapy, University Hospital Brno
Accession: SCV000540894.1
First in ClinVar: Jul 29, 2016 Last updated: Jul 29, 2016 |
Number of individuals with the variant: 1
Clinical Features:
Hypercholesterolemia (present)
Age: 50-59 years
Sex: female
Ethnicity/Population group: Caucasian
Geographic origin: Czech Republic, Europe
Tissue: Whole blood
Method: ADH Master kit (Multiplicom)
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Likely pathogenic
(Oct 23, 2017)
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criteria provided, single submitter
Method: clinical testing
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Hypercholesterolemia, familial, 1
Affected status: unknown
Allele origin:
germline
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Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine
Accession: SCV000839993.1
First in ClinVar: Sep 30, 2017 Last updated: Sep 30, 2017 |
Comment:
This c.1238C>T (p.Thr413Met) variant in the LDLR gene has been reported in multiple individuals with familial hypercholesterolemia (PMID: 11857755, 17539906, 19843101, 11668627, 15015036, 25682026) or … (more)
This c.1238C>T (p.Thr413Met) variant in the LDLR gene has been reported in multiple individuals with familial hypercholesterolemia (PMID: 11857755, 17539906, 19843101, 11668627, 15015036, 25682026) or myocardial infarction (PMID: 25487149). The p.Thr413Met variant occurs within the low-density lipoprotein receptor repeat class B domain of the LDLR protein (https://www.ncbi.nlm.nih.gov/Structure/cdd/wrpsb.cgi?seqinput=NP_001182729.1 ). The c.1238C>T variant is rare in the general population and threonine at position 413 of the LDLR protein is highly evolutionarily conserved. The c.1238C>T (p.Thr413Met) variant in the LDLR gene is classified as likely pathogenic. (less)
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Likely pathogenic
(Jan 26, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not provided
Affected status: yes
Allele origin:
germline
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AiLife Diagnostics, AiLife Diagnostics
Accession: SCV002502862.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
Number of individuals with the variant: 1
Secondary finding: no
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Likely pathogenic
(Dec 12, 2022)
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criteria provided, single submitter
Method: clinical testing
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Familial hypercholesterolemia
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV002819468.1
First in ClinVar: Jan 15, 2023 Last updated: Jan 15, 2023 |
Comment:
Variant summary: LDLR c.1238C>T (p.Thr413Met) results in a non-conservative amino acid change located in the EGF spacer domain (Dong_2022) of the encoded protein sequence. Five … (more)
Variant summary: LDLR c.1238C>T (p.Thr413Met) results in a non-conservative amino acid change located in the EGF spacer domain (Dong_2022) of 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 2.8e-05 in 253468 control chromosomes (gnomAD and publication data). c.1238C>T has been reported in the literature in individuals affected with Familial Hypercholesterolemia, Myocardial infarction or Coronary artery disease (Bunn_2022, Leren_2004, Taylor_2007, Hooper_2012, Do_2014, Khera_2016, Wald_2016, Saadatagah_2021, Sturm_2021). These data indicate that the variant is likely to be associated with disease. At least one functional study showed LDLR activity (LDL binding and uptake) of this variant determined by flow cytometry and indicated LDL uptake as 85% WT and LDL binding as 80% WT, but no effect on protein expression level in transfected cellls (Galicia-Garcia_2020). Twelve ClinVar submitters (evaluation after 2014) cite this variant as uncertain significance (n=3), likely pathogenic (n=8) and pathogenic (n=1), including one expert panel (ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel) classified it as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. (less)
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Likely pathogenic
(May 08, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hypercholesterolemia, familial, 1
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
unknown
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Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV004027629.1
First in ClinVar: Aug 26, 2023 Last updated: Aug 26, 2023 |
Comment:
Criteria applied: PS4_MOD,PM2_SUP,PP1,PP3,PP4
Clinical Features:
Intellectual disability, mild (present) , Focal-onset seizure (present)
Sex: male
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Pathogenic
(Jan 23, 2024)
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criteria provided, single submitter
Method: clinical testing
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Familial hypercholesterolemia
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000948046.6
First in ClinVar: Aug 14, 2019 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 413 of the LDLR protein (p.Thr413Met). … (more)
This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 413 of the LDLR protein (p.Thr413Met). This variant is present in population databases (rs368562025, gnomAD 0.01%), including at least one homozygous and/or hemizygous individual. This missense change has been observed in individual(s) with familial hypercholesterolemia (PMID: 11857755, 20236128, 25682026; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 161276). 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%. For these reasons, this variant has been classified as Pathogenic. (less)
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Likely pathogenic
(May 09, 2023)
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criteria provided, single submitter
Method: clinical testing
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Familial hypercholesterolemia
Affected status: unknown
Allele origin:
germline
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Color Diagnostics, LLC DBA Color Health
Accession: SCV000909161.4
First in ClinVar: May 20, 2019 Last updated: Feb 14, 2024 |
Comment:
This missense variant (also known as p.Thr392Met in the mature protein) replaces threonine with methionine at codon 413 in the LDLR type B repeat 1 … (more)
This missense variant (also known as p.Thr392Met in the mature protein) replaces threonine with methionine at codon 413 in the LDLR type B repeat 1 of the EGF precursor homology domain of the LDLR protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Functional studies have indicated no significant change in LDLR protein expression and function due to this variant (PMID: 32015373, 34029164). This variant has been reported in over twenty heterozygous individuals affected with familial hypercholesterolemia (PMID: 11668627, 11857755, 15015036, 15199436, 15576851, 17539906, 19843101, 22883975, 25682026, 31993549, 34037665; ClinVar SCV001960926.1). It has also been reported in an individual affected with myocardial infarction (PMID: 25487149) and in an individual affected with low circulating HDL-C (PMID: 35460704). This variant has also been observed in compound heterozygous state with a known pathogenic LDLR variant in an individual affected with severe homozygous familial hypercholesterolemia, a phenotype expected of having two deleterious LDLR variants (PMID: 34029164). This variant has been reported to segregate with disease in two members of a family (ClinVar SCV001960926.1). This variant has been identified in 7/251176 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Likely Pathogenic. (less)
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Likely pathogenic
(Feb 01, 2023)
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criteria provided, single submitter
Method: clinical testing
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Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV002662751.4
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The p.T413M variant (also known as c.1238C>T), located in coding exon 9 of the LDLR gene, results from a C to T substitution at nucleotide … (more)
The p.T413M variant (also known as c.1238C>T), located in coding exon 9 of the LDLR gene, results from a C to T substitution at nucleotide position 1238. The threonine at codon 413 is replaced by methionine, an amino acid with similar properties. This variant (also described as p.T392M) has been detected in individuals with familial hypercholesterolemia (FH); however, clinical details were limited in most cases (Bunn CF et al. Hum. Mutat., 2002 Mar;19:311; Leren TP et al. Semin Vasc Med, 2004 Feb;4:75-85; Taylor A et al. Clin. Genet., 2007 Jun;71:561-8; Safarova MS et al. Eur. J. Hum. Genet., 2017 04;25:410-415). This variant has also been seen in an exome cohort, but cardiovascular history was not provided (Dorschner MO et al. Am. J. Hum. Genet., 2013 Oct;93:631-40; Amendola LM et al. Genome Res., 2015 Mar;25:305-15; Do R et al. Nature, 2015 Feb;518:102-6). This alteration was also detected in one control subject from a myocardial infarction study (Khera AV et al. Circulation, 2019 03;139:1593-1602). This alteration has also been reported in additional subjects with FH and as a compound heterozygote in a child with features of FH (personal communication). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. (less)
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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
|
CSER _CC_NCGL, University of Washington
Study: ESP 6500 variant annotation
Accession: SCV000190296.1 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
(Jun 05, 2008)
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no assertion criteria provided
Method: clinical testing
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Familial hypercholesterolemia
Affected status: yes
Allele origin:
germline
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Cardiovascular Genetics Laboratory, PathWest Laboratory Medicine WA - Fiona Stanley Hospital
Accession: SCV000268607.1
First in ClinVar: May 21, 2016 Last updated: May 21, 2016 |
Number of individuals with the variant: 2
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Likely pathogenic
(Aug 13, 2020)
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no assertion criteria provided
Method: clinical testing
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Familial hypercholesterolemia
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV002086415.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
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Pathogenic
(-)
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no assertion criteria provided
Method: research
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Familial hypercholesterolemia
Affected status: unknown
Allele origin:
germline
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Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum
Accession: SCV000606368.1
First in ClinVar: Sep 30, 2017 Last updated: Sep 30, 2017 |
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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. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Whole-exome sequencing reveals damaging gene variants associated with hypoalphalipoproteinemia. | Dong W | Journal of lipid research | 2022 | PMID: 35460704 |
Polygenic architecture and cardiovascular risk of familial combined hyperlipidemia. | Trinder M | Atherosclerosis | 2022 | PMID: 34906840 |
The Clinical Genome Resource (ClinGen) Familial Hypercholesterolemia Variant Curation Expert Panel consensus guidelines for LDLR variant classification. | Chora JR | Genetics in medicine : official journal of the American College of Medical Genetics | 2022 | PMID: 34906454 |
Limited-Variant Screening vs Comprehensive Genetic Testing for Familial Hypercholesterolemia Diagnosis. | Sturm AC | JAMA cardiology | 2021 | PMID: 34037665 |
Cohort Generation and Characterization of Patient-Specific Familial Hypercholesterolemia Induced Pluripotent Stem Cells. | Omer L | Stem cells and development | 2021 | PMID: 34029164 |
Genetic basis of hypercholesterolemia in adults. | Saadatagah S | NPJ genomic medicine | 2021 | PMID: 33854068 |
Population genetic screening efficiently identifies carriers of autosomal dominant diseases. | Grzymski JJ | Nature medicine | 2020 | PMID: 32719484 |
Familial Hypercholesterolemia in a Healthy Elderly Population. | Lacaze P | Circulation. Genomic and precision medicine | 2020 | PMID: 32522009 |
Mutation type classification and pathogenicity assignment of sixteen missense variants located in the EGF-precursor homology domain of the LDLR. | Galicia-Garcia U | Scientific reports | 2020 | PMID: 32015373 |
Molecular Characterization of Familial Hypercholesterolemia in a North American Cohort. | Garg A | Journal of the Endocrine Society | 2019 | PMID: 31993549 |
Harmonizing Clinical Sequencing and Interpretation for the eMERGE III Network. | eMERGE Consortium. Electronic address: agibbs@bcm.edu | American journal of human genetics | 2019 | PMID: 31447099 |
Whole-Genome Sequencing to Characterize Monogenic and Polygenic Contributions in Patients Hospitalized With Early-Onset Myocardial Infarction. | Khera AV | Circulation | 2019 | PMID: 30586733 |
Variability in assigning pathogenicity to incidental findings: insights from LDLR sequence linked to the electronic health record in 1013 individuals. | Safarova MS | European journal of human genetics : EJHG | 2017 | PMID: 28145427 |
Child-Parent Familial Hypercholesterolemia Screening in Primary Care. | Wald DS | The New England journal of medicine | 2016 | PMID: 27783906 |
Diagnostic Yield and Clinical Utility of Sequencing Familial Hypercholesterolemia Genes in Patients With Severe Hypercholesterolemia. | Khera AV | Journal of the American College of Cardiology | 2016 | PMID: 27050191 |
Would raising the total cholesterol diagnostic cut-off from 7.5 mmol/L to 9.3 mmol/L improve detection rate of patients with monogenic familial hypercholesterolaemia? | Futema M | Atherosclerosis | 2015 | PMID: 25682026 |
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 |
Actionable, pathogenic incidental findings in 1,000 participants' exomes. | Dorschner MO | American journal of human genetics | 2013 | PMID: 24055113 |
Genetic analysis of familial hypercholesterolaemia in Western Australia. | Hooper AJ | Atherosclerosis | 2012 | PMID: 22883975 |
Mutation detection rate and spectrum in familial hypercholesterolaemia patients in the UK pilot cascade project. | Taylor A | Clinical genetics | 2010 | PMID: 20236128 |
Mutation screening in patients for familial hypercholesterolaemia (ADH). | Taylor A | Clinical genetics | 2010 | PMID: 19843101 |
Multiplex ARMS analysis to detect 13 common mutations in familial hypercholesterolaemia. | Taylor A | Clinical genetics | 2007 | PMID: 17539906 |
Multiplex ligation-dependent probe amplification of LDLR enhances molecular diagnosis of familial hypercholesterolemia. | Wang J | Journal of lipid research | 2005 | PMID: 15576851 |
Application of molecular genetics for diagnosing familial hypercholesterolemia in Norway: results from a family-based screening program. | Leren TP | Seminars in vascular medicine | 2004 | PMID: 15199436 |
Screening for point mutations in the LDL receptor gene in Bulgarian patients with severe hypercholesterolemia. | Mihaylov VA | Journal of human genetics | 2004 | PMID: 15015036 |
Comparison of SSCP and DHPLC for the detection of LDLR mutations in a New Zealand cohort. | Bunn CF | Human mutation | 2002 | PMID: 11857755 |
Low density lipoprotein receptor (LDLR) gene mutations in Canadian subjects with familial hypercholesterolemia, but not of French descent. | Wang J | Human mutation | 2001 | PMID: 11668627 |
Away from a narrow approach. | Owuor E | Kenya nursing journal | 1991 | PMID: 1960926 |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/d0043f81-8599-437b-b1fc-84609ee67f9a | - | - | - | - |
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HelpRecord last updated Oct 13, 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.