The patient has a development delay, dysmorphic features and bilateral cryptorchidism, features consistent with Pitt-Hopkins syndrome. This present variant, which is predicted to generate a truncated non-functional TCF4 protein, has not yet been reported, but it is widely accepted that loss of function mutations in the TCF4 gene cause Pitt-Hopkins syndrome.
ClinVar Genomic variation as it relates to human health
NM_001083962.2(TCF4):c.1136dup (p.Leu379fs)
Germline
Classification
Help
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.
(1)
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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.
Likely pathogenic
1
criteria provided, single submitter
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_001083962.2(TCF4):c.1136dup (p.Leu379fs)
Variation ID: 375631 Accession: VCV000375631.1
- Type and length
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Duplication, 1 bp
- Location
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Cytogenetic: 18q21.2 18: 55257324-55257325 (GRCh38) [ NCBI UCSC ] 18: 52924555-52924556 (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 Feb 17, 2017 Feb 17, 2017 Oct 23, 2015 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001083962.2:c.1136dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001077431.1:p.Leu379fs frameshift NM_001243226.3:c.1442dup NP_001230155.2:p.Leu481fs frameshift NM_001243227.2:c.1064dup NP_001230156.1:p.Leu355fs frameshift NM_001243228.2:c.1154dup NP_001230157.1:p.Leu385fs frameshift NM_001243230.2:c.1127dup NP_001230159.1:p.Leu376fs frameshift NM_001243231.2:c.1010dup NP_001230160.1:p.Leu337fs frameshift NM_001243232.1:c.923dup NP_001230161.1:p.Leu308fs frameshift NM_001243233.2:c.746dup NP_001230162.1:p.Leu249fs frameshift NM_001243234.2:c.656dup NP_001230163.1:p.Leu219fs frameshift NM_001243235.2:c.656dup NP_001230164.1:p.Leu219fs frameshift NM_001243236.2:c.656dup NP_001230165.1:p.Leu219fs frameshift NM_001306207.1:c.1064dup NP_001293136.1:p.Leu355fs frameshift NM_001306208.1:c.923dup NP_001293137.1:p.Leu308fs frameshift NM_001330604.3:c.1133dup NP_001317533.1:p.Leu378fs frameshift NM_001330605.3:c.746dup NP_001317534.1:p.Leu249fs frameshift NM_001348211.2:c.1010dup NP_001335140.1:p.Leu337fs frameshift NM_001348212.2:c.746dup NP_001335141.1:p.Leu249fs frameshift NM_001348213.2:c.746dup NP_001335142.1:p.Leu249fs frameshift NM_001348214.2:c.653dup NP_001335143.1:p.Leu218fs frameshift NM_001348215.2:c.488dup NP_001335144.1:p.Leu163fs frameshift NM_001348216.2:c.656dup NP_001335145.1:p.Leu219fs frameshift NM_001348217.1:c.1064dup NP_001335146.1:p.Leu355fs frameshift NM_001348218.2:c.1064dup NP_001335147.1:p.Leu355fs frameshift NM_001348219.2:c.1064dup NP_001335148.1:p.Leu355fs frameshift NM_001348220.1:c.1061dup NP_001335149.1:p.Leu354fs frameshift NM_001369567.1:c.1136dup NP_001356496.1:p.Leu379fs frameshift NM_001369568.1:c.1136dup NP_001356497.1:p.Leu379fs frameshift NM_001369569.1:c.1133dup NP_001356498.1:p.Leu378fs frameshift NM_001369570.1:c.1133dup NP_001356499.1:p.Leu378fs frameshift NM_001369571.1:c.1136dup NP_001356500.1:p.Leu379fs frameshift NM_001369572.1:c.1136dup NP_001356501.1:p.Leu379fs frameshift NM_001369573.1:c.1133dup NP_001356502.1:p.Leu378fs frameshift NM_001369574.1:c.1133dup NP_001356503.1:p.Leu378fs frameshift NM_001369575.1:c.1064dup NP_001356504.1:p.Leu355fs frameshift NM_001369576.1:c.1061dup NP_001356505.1:p.Leu354fs frameshift NM_001369577.1:c.1061dup NP_001356506.1:p.Leu354fs frameshift NM_001369578.1:c.1061dup NP_001356507.1:p.Leu354fs frameshift NM_001369579.1:c.1061dup NP_001356508.1:p.Leu354fs frameshift NM_001369580.1:c.1061dup NP_001356509.1:p.Leu354fs frameshift NM_001369581.1:c.1061dup NP_001356510.1:p.Leu354fs frameshift NM_001369582.1:c.1064dup NP_001356511.1:p.Leu355fs frameshift NM_001369583.1:c.1064dup NP_001356512.1:p.Leu355fs frameshift NM_001369584.1:c.1061dup NP_001356513.1:p.Leu354fs frameshift NM_001369585.1:c.1061dup NP_001356514.1:p.Leu354fs frameshift NM_001369586.1:c.1067dup NP_001356515.1:p.Leu356fs frameshift NM_003199.3:c.1136dup NP_003190.1:p.Leu379fs frameshift NC_000018.10:g.55257326dup NC_000018.9:g.52924557dup NG_011716.2:g.383669dup - Protein change
- L163fs, L218fs, L249fs, L354fs, L376fs, L379fs, L481fs, L337fs, L308fs, L356fs, L385fs, L219fs, L355fs, L378fs
- Other names
- -
- Canonical SPDI
- NC_000018.10:55257324:AA:AAA
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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.
- -
- Links
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 | ||
|---|---|---|---|---|---|---|
| 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. |
|||
| TCF4 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
986 | 1213 | |
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. |
|---|---|---|---|---|
| Likely pathogenic (1) |
criteria provided, single submitter
|
Oct 23, 2015 | RCV000417112.1 |
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
(Oct 23, 2015)
|
criteria provided, single submitter
(ACMG Guidelines, 2015)
Method: clinical testing
|
Pitt-Hopkins syndrome
Affected status: yes
Allele origin:
de novo
|
Center of Genomic medicine, Geneva, University Hospital of Geneva
Accession: SCV000494647.1
First in ClinVar: Feb 17, 2017 Last updated: Feb 17, 2017 |
Comment:
The patient has a development delay, dysmorphic features and bilateral cryptorchidism, features consistent with Pitt-Hopkins syndrome. This present variant, which is predicted to generate a … (more)
The patient has a development delay, dysmorphic features and bilateral cryptorchidism, features consistent with Pitt-Hopkins syndrome. This present variant, which is predicted to generate a truncated non-functional TCF4 protein, has not yet been reported, but it is widely accepted that loss of function mutations in the TCF4 gene cause Pitt-Hopkins syndrome. (less)
Age: 0-9 years
Sex: male
|
Comment:
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. |
Comment:
The patient has a development delay, dysmorphic features and bilateral cryptorchidism, features consistent with Pitt-Hopkins syndrome. This present variant, which is predicted to generate a truncated non-functional TCF4 protein, has not yet been reported, but it is widely accepted that loss of function mutations in the TCF4 gene cause Pitt-Hopkins syndrome.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Functional analysis of TCF4 missense mutations that cause Pitt-Hopkins syndrome. | Forrest M | Human mutation | 2012 | PMID: 22777675 |
Text-mined citations for rs1057519592 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Apr 25, 2022
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.