ClinVar Genomic variation as it relates to human health
NM_000527.5(LDLR):c.694+25C>T
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.694+25C>T
Variation ID: 251406 Accession: VCV000251406.19
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 19p13.2 19: 11105625 (GRCh38) [ NCBI UCSC ] 19: 11216301 (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 Aug 13, 2017 Feb 28, 2024 Apr 28, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000527.5:c.694+25C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
intron variant NM_001195798.2:c.694+25C>T intron variant NM_001195799.2:c.571+25C>T intron variant NM_001195800.2:c.314-1767C>T intron variant NM_001195803.2:c.314-940C>T intron variant NC_000019.10:g.11105625C>T NC_000019.9:g.11216301C>T NG_009060.1:g.21245C>T LRG_274:g.21245C>T LRG_274t1:c.694+25C>T - Protein change
- Other names
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- Canonical SPDI
- NC_000019.10:11105624: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
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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 |
3895 | 4139 |
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
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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Uncertain significance (3) |
reviewed by expert panel
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Apr 28, 2023 | RCV000238457.6 | |
Likely benign (1) |
criteria provided, single submitter
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Jan 14, 2018 | RCV000606160.1 | |
Benign (2) |
criteria provided, single submitter
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Nov 13, 2023 | RCV000858461.10 | |
Likely benign (2) |
no assertion criteria provided
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- | RCV001699250.3 |
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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Uncertain significance
(Apr 28, 2023)
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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
Accession: SCV004022451.1
First in ClinVar: Aug 05, 2023 Last updated: Aug 05, 2023 |
Comment:
The NM_000527.5(LDLR):c.694+25C>T variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence code BP4 as defined by the ClinGen Familial … (more)
The NM_000527.5(LDLR):c.694+25C>T variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence code BP4 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1016/j.gim.2021.09.012). The supporting evidence is as follows: BP4: The variant is not predicted to affect the splicing process by SpliceAI. So, BP4 is met. (less)
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Likely benign
(Mar 25, 2016)
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criteria provided, single submitter
Method: literature only
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Familial hypercholesterolemia
Affected status: yes
Allele origin:
germline
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LDLR-LOVD, British Heart Foundation
Accession: SCV000294922.2
First in ClinVar: Jul 29, 2016 Last updated: Dec 26, 2017 |
Observation 1:
Number of individuals with the variant: 1
Observation 2:
Number of individuals with the variant: 1
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Uncertain significance
(Mar 01, 2016)
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criteria provided, single submitter
Method: research
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Familial hypercholesterolemia
Affected status: unknown
Allele origin:
germline
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Laboratory of Genetics and Molecular Cardiology, University of São Paulo
Study: HipercolBrasil
Accession: SCV000588514.1 First in ClinVar: Aug 13, 2017 Last updated: Aug 13, 2017 |
Comment on evidence:
%MAF(ExAC):0.08313
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Likely benign
(Jan 14, 2018)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000730506.1
First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
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Benign
(Nov 13, 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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Invitae
Accession: SCV000556783.8
First in ClinVar: Jul 29, 2016 Last updated: Feb 28, 2024 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001918531.1 First in ClinVar: Sep 25, 2021 Last updated: Sep 25, 2021 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001962779.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
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Likely benign
(Nov 09, 2019)
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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: SCV002086385.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
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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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Spectrum of mutations and phenotypic expression in patients with autosomal dominant hypercholesterolemia identified in Italy. | Bertolini S | Atherosclerosis | 2013 | PMID: 23375686 |
Molecular genetics of familial hypercholesterolemia in Spain: Ten novel LDLR mutations and population analysis. | García-García AB | Human mutation | 2001 | PMID: 11668640 |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/56aaefac-d400-4477-a67e-91703e9a8be8 | - | - | - | - |
Text-mined citations for this variant ...
HelpRecord last updated Mar 05, 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.