ClinVar Genomic variation as it relates to human health
NM_000527.5(LDLR):c.1211C>T (p.Thr404Ile)
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.1211C>T (p.Thr404Ile)
Variation ID: 251736 Accession: VCV000251736.2
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 19p13.2 19: 11113302 (GRCh38) [ NCBI UCSC ] 19: 11223978 (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 8, 2021 May 24, 2021 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000527.5:c.1211C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000518.1:p.Thr404Ile missense NM_001195798.2:c.1211C>T NP_001182727.1:p.Thr404Ile missense NM_001195799.2:c.1088C>T NP_001182728.1:p.Thr363Ile missense NM_001195800.2:c.707C>T NP_001182729.1:p.Thr236Ile missense NM_001195803.2:c.830C>T NP_001182732.1:p.Thr277Ile missense NC_000019.10:g.11113302C>T NC_000019.9:g.11223978C>T NG_009060.1:g.28922C>T LRG_274:g.28922C>T LRG_274t1:c.1211C>T LRG_274p1:p.Thr404Ile - Protein change
- T404I, T236I, T363I, T277I
- Other names
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- Canonical SPDI
- NC_000019.10:11113301: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.
Trans-Omics for Precision Medicine (TOPMed) 0.00000
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
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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
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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/Likely pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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May 24, 2021 | RCV000237211.4 |
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
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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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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: SCV000295302.2
First in ClinVar: Jul 29, 2016 Last updated: May 03, 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
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Pathogenic
(Mar 01, 2016)
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criteria provided, single submitter
Method: curation, literature only
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Familial hypercholesterolemia
(Autosomal dominant inheritance)
Affected status: unknown, not applicable
Allele origin:
germline,
not applicable
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Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge
Accession: SCV000599367.1
First in ClinVar: Jul 29, 2016 Last updated: Jul 29, 2016 |
Observation 1: Observation 2:
Comment on evidence:
Assay Description:Heterologous cells (HEK 293), WB, FACS assays
Result:
Normal cell surface LDLR; ~70% LDL-LDLR binding and uptake
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Likely pathogenic
(May 24, 2021)
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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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Laboratory of molecular diagnosis of dyslipidemias, Università egli studi di Napoli Federico II
Accession: SCV001653627.1
First in ClinVar: Jun 08, 2021 Last updated: Jun 08, 2021 |
Number of individuals with the variant: 2
Ethnicity/Population group: Caucasian
Geographic origin: Italy
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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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Lipid profile and genetic status in a familial hypercholesterolemia pediatric population: exploring the LDL/HDL ratio. | Di Taranto MD | Clinical chemistry and laboratory medicine | 2019 | PMID: 30710474 |
Spectrum of mutations in Italian patients with familial hypercholesterolemia: New results from the LIPIGEN study. | Pirillo A | Atherosclerosis. Supplements | 2017 | PMID: 28965616 |
Spectrum of mutations and phenotypic expression in patients with autosomal dominant hypercholesterolemia identified in Italy. | Bertolini S | Atherosclerosis | 2013 | PMID: 23375686 |
Novel and recurrent LDLR gene mutations in Pakistani hypercholesterolemia patients. | Ahmed W | Molecular biology reports | 2012 | PMID: 22311046 |
The type of LDLR gene mutation predicts cardiovascular risk in children with familial hypercholesterolemia. | Guardamagna O | The Journal of pediatrics | 2009 | PMID: 19446849 |
Mutations in the LDL receptor gene in four Chinese homozygous familial hypercholesterolemia phenotype patients. | Wang L | Nutrition, metabolism, and cardiovascular diseases : NMCD | 2009 | PMID: 19073363 |
Analysis of low-density lipoprotein receptor gene mutations in a Chinese patient with clinically homozygous familial hypercholesterolemia. | Cao S | Chinese medical journal | 2003 | PMID: 14570618 |
Text-mined citations for rs879254835 ...
HelpRecord last updated Jun 23, 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.