ClinVar Genomic variation as it relates to human health
NM_000527.5(LDLR):c.2439G>A (p.Trp813Ter)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000527.5(LDLR):c.2439G>A (p.Trp813Ter)
Variation ID: 3703 Accession: VCV000003703.2
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 19p13.2 19: 11129562 (GRCh38) [ NCBI UCSC ] 19: 11240238 (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 Jul 29, 2016 Jun 23, 2019 Mar 25, 2016 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000527.5:c.2439G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000518.1:p.Trp813Ter nonsense NM_001195798.2:c.2439G>A NP_001182727.1:p.Trp813Ter nonsense NM_001195799.2:c.2316G>A NP_001182728.1:p.Trp772Ter nonsense NM_001195800.2:c.1935G>A NP_001182729.1:p.Trp645Ter nonsense NM_001195803.2:c.1905G>A NP_001182732.1:p.Trp635Ter nonsense NC_000019.10:g.11129562G>A NC_000019.9:g.11240238G>A NG_009060.1:g.45182G>A LRG_274:g.45182G>A LRG_274t1:c.2439G>A LRG_274p1:p.Trp813Ter - Protein change
- W813*, W635*, W645*, W772*
- Other names
- W792*
- FH Bahrain
- Canonical SPDI
- NC_000019.10:11129561:G:A
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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
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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 |
4070 | 4346 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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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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Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Mar 25, 2016 | RCV000003892.6 |
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
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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
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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
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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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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: SCV000296009.2
First in ClinVar: Jul 29, 2016 Last updated: Jul 29, 2016 |
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
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Pathogenic
(Mar 01, 2016)
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criteria provided, single submitter
Method: research
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Familial hypercholesterolemia
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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Fundacion Hipercolesterolemia Familiar
Study: SAFEHEART
Accession: SCV000607707.1 First in ClinVar: Jul 29, 2016 Last updated: Jul 29, 2016 |
Observation 1: Observation 2:
Comment on evidence:
Hmz patients' fibroblasts, 125I-LDL assays
Result:
30% LDL-LDLR binding, 2-5% LDL-LDLR uptake, <2% LDLR degradation
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Pathogenic
(Jul 01, 1991)
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no assertion criteria provided
Method: literature only
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FH BAHRAIN
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000024057.2
First in ClinVar: Apr 04, 2013 Last updated: Jun 23, 2019 |
Comment on evidence:
In a Bahraini patient with FH (FHCL1; 143890), Lehrman et al. (1985) found a change in the tryptophan-792 codon to a stop codon as the … (more)
In a Bahraini patient with FH (FHCL1; 143890), Lehrman et al. (1985) found a change in the tryptophan-792 codon to a stop codon as the basis of this variant. Truncation of the cytoplasmic domain of the LDLR protein results in defective internalization. Recurrence of this mutation was observed by Loux et al. (1991) in the course of a survey of 139 unrelated French FH subjects. (less)
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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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Genetic diagnosis of familial hypercholesterolemia using a DNA-array based platform. | Alonso R | Clinical biochemistry | 2009 | PMID: 19318025 |
Multiplex ARMS analysis to detect 13 common mutations in familial hypercholesterolaemia. | Taylor A | Clinical genetics | 2007 | PMID: 17539906 |
Spectrum of LDL receptor gene mutations in Denmark: implications for molecular diagnostic strategy in heterozygous familial hypercholesterolemia. | Jensen HK | Atherosclerosis | 1999 | PMID: 10532689 |
Recurrent mutation at aa 792 in the LDL receptor gene in a French patient. | Loux N | Human genetics | 1991 | PMID: 1677927 |
Internalization-defective LDL receptors produced by genes with nonsense and frameshift mutations that truncate the cytoplasmic domain. | Lehrman MA | Cell | 1985 | PMID: 3924410 |
Text-mined citations for rs121908032 ...
HelpRecord last updated Aug 06, 2023
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.