Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. ClinVar contains an entry for this variant (Variation ID: 1164050). This variant has not been reported in the literature in individuals affected with TCF4-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 606 of the TCF4 protein (p.Thr606Ile).
ClinVar Genomic variation as it relates to human health
NM_001083962.2(TCF4):c.1817C>T (p.Thr606Ile)
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.
(2)
Help
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.
Uncertain significance
2
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.1817C>T (p.Thr606Ile)
Variation ID: 1164050 Accession: VCV001164050.4
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 18q21.2 18: 55228909 (GRCh38) [ NCBI UCSC ] 18: 52896140 (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 Dec 12, 2021 Feb 20, 2024 Aug 9, 2022 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001083962.2:c.1817C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001077431.1:p.Thr606Ile missense NM_001243226.3:c.2123C>T NP_001230155.2:p.Thr708Ile missense NM_001243227.2:c.1745C>T NP_001230156.1:p.Thr582Ile missense NM_001243228.2:c.1835C>T NP_001230157.1:p.Thr612Ile missense NM_001243230.2:c.1796C>T NP_001230159.1:p.Thr599Ile missense NM_001243231.2:c.1679C>T NP_001230160.1:p.Thr560Ile missense NM_001243232.1:c.1604C>T NP_001230161.1:p.Thr535Ile missense NM_001243233.2:c.1415C>T NP_001230162.1:p.Thr472Ile missense NM_001243234.2:c.1337C>T NP_001230163.1:p.Thr446Ile missense NM_001243235.2:c.1325C>T NP_001230164.1:p.Thr442Ile missense NM_001243236.2:c.1325C>T NP_001230165.1:p.Thr442Ile missense NM_001306207.1:c.1733C>T NP_001293136.1:p.Thr578Ile missense NM_001306208.1:c.1592C>T NP_001293137.1:p.Thr531Ile missense NM_001330604.3:c.1814C>T NP_001317533.1:p.Thr605Ile missense NM_001330605.3:c.1427C>T NP_001317534.1:p.Thr476Ile missense NM_001348211.2:c.1691C>T NP_001335140.1:p.Thr564Ile missense NM_001348212.2:c.1415C>T NP_001335141.1:p.Thr472Ile missense NM_001348213.2:c.1427C>T NP_001335142.1:p.Thr476Ile missense NM_001348214.2:c.1322C>T NP_001335143.1:p.Thr441Ile missense NM_001348215.2:c.1169C>T NP_001335144.1:p.Thr390Ile missense NM_001348216.2:c.1337C>T NP_001335145.1:p.Thr446Ile missense NM_001348217.1:c.1745C>T NP_001335146.1:p.Thr582Ile missense NM_001348218.2:c.1745C>T NP_001335147.1:p.Thr582Ile missense NM_001348219.2:c.1733C>T NP_001335148.1:p.Thr578Ile missense NM_001348220.1:c.1730C>T NP_001335149.1:p.Thr577Ile missense NM_001369567.1:c.1817C>T NP_001356496.1:p.Thr606Ile missense NM_001369568.1:c.1817C>T NP_001356497.1:p.Thr606Ile missense NM_001369569.1:c.1814C>T NP_001356498.1:p.Thr605Ile missense NM_001369570.1:c.1814C>T NP_001356499.1:p.Thr605Ile missense NM_001369571.1:c.1805C>T NP_001356500.1:p.Thr602Ile missense NM_001369572.1:c.1805C>T NP_001356501.1:p.Thr602Ile missense NM_001369573.1:c.1802C>T NP_001356502.1:p.Thr601Ile missense NM_001369574.1:c.1802C>T NP_001356503.1:p.Thr601Ile missense NM_001369575.1:c.1745C>T NP_001356504.1:p.Thr582Ile missense NM_001369576.1:c.1742C>T NP_001356505.1:p.Thr581Ile missense NM_001369577.1:c.1742C>T NP_001356506.1:p.Thr581Ile missense NM_001369578.1:c.1742C>T NP_001356507.1:p.Thr581Ile missense NM_001369579.1:c.1742C>T NP_001356508.1:p.Thr581Ile missense NM_001369580.1:c.1742C>T NP_001356509.1:p.Thr581Ile missense NM_001369581.1:c.1742C>T NP_001356510.1:p.Thr581Ile missense NM_001369582.1:c.1733C>T NP_001356511.1:p.Thr578Ile missense NM_001369583.1:c.1733C>T NP_001356512.1:p.Thr578Ile missense NM_001369584.1:c.1730C>T NP_001356513.1:p.Thr577Ile missense NM_001369585.1:c.1730C>T NP_001356514.1:p.Thr577Ile missense NM_001369586.1:c.1748C>T NP_001356515.1:p.Thr583Ile missense NM_003199.3:c.1805C>T NP_003190.1:p.Thr602Ile missense NC_000018.10:g.55228909G>A NC_000018.9:g.52896140G>A NG_011716.2:g.412085C>T - Protein change
- T390I, T441I, T442I, T446I, T472I, T476I, T531I, T535I, T560I, T564I, T577I, T578I, T581I, T582I, T583I, T599I, T601I, T602I, T605I, T606I, T612I, T708I
- Other names
- -
- Canonical SPDI
- NC_000018.10:55228908: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
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 |
993 | 1220 | |
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. |
|---|---|---|---|---|
| Uncertain significance (2) |
criteria provided, single submitter
|
Aug 9, 2022 | RCV001788532.4 |
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
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. |
|
|---|---|---|---|---|---|
|
Uncertain significance
(Aug 09, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Pitt-Hopkins syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV003321340.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 20, 2024 |
Comment:
Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact … (more)
Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. ClinVar contains an entry for this variant (Variation ID: 1164050). This variant has not been reported in the literature in individuals affected with TCF4-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 606 of the TCF4 protein (p.Thr606Ile). (less)
|
|
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Pathogenic
(May 13, 2021)
|
no assertion criteria provided
Method: clinical testing
|
Pitt-Hopkins syndrome
Affected status: yes
Allele origin:
de novo
|
Pediatric Genetics Clinic, Sheba Medical Center
Accession: SCV001712237.1
First in ClinVar: Dec 12, 2021 Last updated: Dec 12, 2021 |
Clinical Features:
Neurodevelopmental delay (present) , Seizure (present) , Abnormal facial shape (present) , Ventriculomegaly (present)
Secondary finding: no
|
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:
Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. ClinVar contains an entry for this variant (Variation ID: 1164050). This variant has not been reported in the literature in individuals affected with TCF4-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 606 of the TCF4 protein (p.Thr606Ile).
Citations for germline classification of this variant
Help| There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for rs2144403104 ...
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 Sep 29, 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.