ClinVar Genomic variation as it relates to human health
NM_001083962.2(TCF4):c.178G>A (p.Gly60Arg)
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_001083962.2(TCF4):c.178G>A (p.Gly60Arg)
Variation ID: 1485528 Accession: VCV001485528.6
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 18q21.2 18: 55464105 (GRCh38) [ NCBI UCSC ] 18: 53131336 (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 Mar 28, 2022 Feb 28, 2024 Feb 23, 2021 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001083962.2:c.178G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001077431.1:p.Gly60Arg missense NM_001243226.3:c.484G>A NP_001230155.2:p.Gly162Arg missense NM_001243227.2:c.106G>A NP_001230156.1:p.Gly36Arg missense NM_001243228.2:c.178G>A NP_001230157.1:p.Gly60Arg missense NM_001243230.2:c.172G>A NP_001230159.1:p.Gly58Arg missense NM_001243231.2:c.52G>A NP_001230160.1:p.Gly18Arg missense NM_001306207.1:c.106G>A NP_001293136.1:p.Gly36Arg missense NM_001330604.3:c.178G>A NP_001317533.1:p.Gly60Arg missense NM_001348211.2:c.52G>A NP_001335140.1:p.Gly18Arg missense NM_001348217.1:c.106G>A NP_001335146.1:p.Gly36Arg missense NM_001348218.2:c.106G>A NP_001335147.1:p.Gly36Arg missense NM_001348219.2:c.106G>A NP_001335148.1:p.Gly36Arg missense NM_001348220.1:c.106G>A NP_001335149.1:p.Gly36Arg missense NM_001369567.1:c.178G>A NP_001356496.1:p.Gly60Arg missense NM_001369568.1:c.178G>A NP_001356497.1:p.Gly60Arg missense NM_001369569.1:c.178G>A NP_001356498.1:p.Gly60Arg missense NM_001369570.1:c.178G>A NP_001356499.1:p.Gly60Arg missense NM_001369571.1:c.178G>A NP_001356500.1:p.Gly60Arg missense NM_001369572.1:c.178G>A NP_001356501.1:p.Gly60Arg missense NM_001369573.1:c.178G>A NP_001356502.1:p.Gly60Arg missense NM_001369574.1:c.178G>A NP_001356503.1:p.Gly60Arg missense NM_001369575.1:c.106G>A NP_001356504.1:p.Gly36Arg missense NM_001369576.1:c.106G>A NP_001356505.1:p.Gly36Arg missense NM_001369577.1:c.106G>A NP_001356506.1:p.Gly36Arg missense NM_001369578.1:c.106G>A NP_001356507.1:p.Gly36Arg missense NM_001369579.1:c.106G>A NP_001356508.1:p.Gly36Arg missense NM_001369580.1:c.106G>A NP_001356509.1:p.Gly36Arg missense NM_001369581.1:c.106G>A NP_001356510.1:p.Gly36Arg missense NM_001369582.1:c.106G>A NP_001356511.1:p.Gly36Arg missense NM_001369583.1:c.106G>A NP_001356512.1:p.Gly36Arg missense NM_001369584.1:c.106G>A NP_001356513.1:p.Gly36Arg missense NM_001369585.1:c.106G>A NP_001356514.1:p.Gly36Arg missense NM_001369586.1:c.106G>A NP_001356515.1:p.Gly36Arg missense NM_003199.3:c.178G>A NP_003190.1:p.Gly60Arg missense NC_000018.10:g.55464105C>T NC_000018.9:g.53131336C>T NG_011716.2:g.176889G>A - Protein change
- G36R, G58R, G162R, G18R, G60R
- Other names
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- Canonical SPDI
- NC_000018.10:55464104: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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- Links
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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TCF4 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
960 | 1185 | |
TCF4-AS1 | - | - | - | GRCh38 | - | 110 |
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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Likely pathogenic (1) |
criteria provided, single submitter
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Feb 23, 2021 | RCV002000804.5 |
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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Likely pathogenic
(Feb 23, 2021)
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criteria provided, single submitter
Method: clinical testing
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Pitt-Hopkins syndrome
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV002277484.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 28, 2024 |
Comment:
In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has … (more)
In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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"). This variant has been observed in individual(s) with clinical features of TCF4-related conditions (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with arginine at codon 60 of the TCF4 protein (p.Gly60Arg). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and arginine. (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
HelpThere 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 rs2144897134 ...
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.