ClinVar Genomic variation as it relates to human health
NM_001174096.2(ZEB1):c.1579dup (p.Val527fs)
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_001174096.2(ZEB1):c.1579dup (p.Val527fs)
Variation ID: 437319 Accession: VCV000437319.7
- Type and length
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Duplication, 1 bp
- Location
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Cytogenetic: 10p11.22 10: 31520904-31520905 (GRCh38) [ NCBI UCSC ] 10: 31809832-31809833 (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 28, 2017 Feb 14, 2024 Oct 18, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001174096.2:c.1579dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001167567.1:p.Val527fs frameshift NM_001128128.3:c.1528dup NP_001121600.1:p.Val510fs frameshift NM_001174093.2:c.1516dup NP_001167564.1:p.Val506fs frameshift NM_001174094.2:c.1525dup NP_001167565.1:p.Val509fs frameshift NM_001174095.2:c.1375dup NP_001167566.1:p.Val459fs frameshift NM_001323638.2:c.922dup NP_001310567.1:p.Val308fs frameshift NM_001323641.2:c.922dup NP_001310570.1:p.Val308fs frameshift NM_001323642.2:c.922dup NP_001310571.1:p.Val308fs frameshift NM_001323643.2:c.922dup NP_001310572.1:p.Val308fs frameshift NM_001323644.2:c.922dup NP_001310573.1:p.Val308fs frameshift NM_001323645.2:c.922dup NP_001310574.1:p.Val308fs frameshift NM_001323646.2:c.922dup NP_001310575.1:p.Val308fs frameshift NM_001323647.2:c.922dup NP_001310576.1:p.Val308fs frameshift NM_001323648.2:c.922dup NP_001310577.1:p.Val308fs frameshift NM_001323649.2:c.922dup NP_001310578.1:p.Val308fs frameshift NM_001323650.2:c.922dup NP_001310579.1:p.Val308fs frameshift NM_001323651.2:c.922dup NP_001310580.1:p.Val308fs frameshift NM_001323652.2:c.922dup NP_001310581.1:p.Val308fs frameshift NM_001323653.2:c.922dup NP_001310582.1:p.Val308fs frameshift NM_001323654.2:c.922dup NP_001310583.1:p.Val308fs frameshift NM_001323655.2:c.922dup NP_001310584.1:p.Val308fs frameshift NM_001323656.2:c.922dup NP_001310585.1:p.Val308fs frameshift NM_001323657.2:c.922dup NP_001310586.1:p.Val308fs frameshift NM_001323658.2:c.922dup NP_001310587.1:p.Val308fs frameshift NM_001323659.2:c.922dup NP_001310588.1:p.Val308fs frameshift NM_001323660.2:c.922dup NP_001310589.1:p.Val308fs frameshift NM_001323661.2:c.922dup NP_001310590.1:p.Val308fs frameshift NM_001323662.2:c.922dup NP_001310591.1:p.Val308fs frameshift NM_001323663.2:c.922dup NP_001310592.1:p.Val308fs frameshift NM_001323664.2:c.922dup NP_001310593.1:p.Val308fs frameshift NM_001323665.2:c.922dup NP_001310594.1:p.Val308fs frameshift NM_001323666.2:c.922dup NP_001310595.1:p.Val308fs frameshift NM_001323671.2:c.922dup NP_001310600.1:p.Val308fs frameshift NM_001323672.2:c.922dup NP_001310601.1:p.Val308fs frameshift NM_001323673.2:c.922dup NP_001310602.1:p.Val308fs frameshift NM_001323674.2:c.1354dup NP_001310603.1:p.Val452fs frameshift NM_001323675.2:c.1312dup NP_001310604.1:p.Val438fs frameshift NM_001323676.2:c.1537dup NP_001310605.1:p.Val513fs frameshift NM_001323677.2:c.1534dup NP_001310606.1:p.Val512fs frameshift NM_001323678.2:c.1303dup NP_001310607.1:p.Val435fs frameshift NM_030751.6:c.1576dup NP_110378.3:p.Val526fs frameshift NC_000010.11:g.31520911dup NC_000010.10:g.31809839dup NG_017048.1:g.206739dup - Protein change
- V438fs, V506fs, V435fs, V459fs, V527fs, V509fs, V308fs, V510fs, V452fs, V512fs, V513fs, V526fs
- Other names
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- Canonical SPDI
- NC_000010.11:31520904:GGGGGGG:GGGGGGGG
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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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ZEB1 | - | - |
GRCh38 GRCh37 |
101 | 119 |
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
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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 (1) |
criteria provided, single submitter
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Jul 5, 2016 | RCV000499953.6 | |
Pathogenic (1) |
criteria provided, single submitter
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Oct 18, 2023 | RCV003558417.1 |
Submissions - Germline
Classification
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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
(Jul 05, 2016)
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criteria provided, single submitter
Method: clinical testing
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Corneal dystrophy
Affected status: yes
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV000598016.1
First in ClinVar: Aug 28, 2017 Last updated: Aug 28, 2017 |
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Pathogenic
(Oct 18, 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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Invitae
Accession: SCV004295652.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Val526Glyfs*3) in the ZEB1 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Val526Glyfs*3) in the ZEB1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ZEB1 are known to be pathogenic (PMID: 16252232, 17935237, 30851240). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with posterior polymorphous corneal dystrophy (PMID: 25441224, 30851240). ClinVar contains an entry for this variant (Variation ID: 437319). For these reasons, this variant has been classified as Pathogenic. (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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The utility of massively parallel sequencing for posterior polymorphous corneal dystrophy type 3 molecular diagnosis. | Dudakova L | Experimental eye research | 2019 | PMID: 30851240 |
Identification of six novel mutations in ZEB1 and description of the associated phenotypes in patients with posterior polymorphous corneal dystrophy 3. | Evans CJ | Annals of human genetics | 2015 | PMID: 25441224 |
Posterior polymorphous corneal dystrophy is associated with TCF8 gene mutations and abdominal hernia. | Aldave AJ | American journal of medical genetics. Part A | 2007 | PMID: 17935237 |
Mutations in TCF8 cause posterior polymorphous corneal dystrophy and ectopic expression of COL4A3 by corneal endothelial cells. | Krafchak CM | American journal of human genetics | 2005 | PMID: 16252232 |
Text-mined citations for rs766305306 ...
HelpRecord last updated Feb 20, 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.