ClinVar Genomic variation as it relates to human health
NM_022445.4(TPK1):c.620A>T (p.Asp207Val)
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_022445.4(TPK1):c.620A>T (p.Asp207Val)
Variation ID: 1048796 Accession: VCV001048796.9
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 7q35 7: 144453657 (GRCh38) [ NCBI UCSC ] 7: 144150750 (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 Apr 13, 2021 Feb 4, 2024 Oct 11, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_022445.4:c.620A>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_071890.2:p.Asp207Val missense NM_001042482.2:c.473A>T NP_001035947.1:p.Asp158Val missense NM_001350879.1:c.620A>T NP_001337808.1:p.Asp207Val missense NM_001350880.1:c.473A>T NP_001337809.1:p.Asp158Val missense NM_001350881.1:c.726A>T NP_001337810.1:p.Ter242Cys stop lost NM_001350882.1:c.605A>T NP_001337811.1:p.Asp202Val missense NM_001350883.1:c.605A>T NP_001337812.1:p.Asp202Val missense NM_001350884.2:c.605A>T NP_001337813.1:p.Asp202Val missense NM_001350885.1:c.302A>T NP_001337814.1:p.Asp101Val missense NM_001350886.1:c.302A>T NP_001337815.1:p.Asp101Val missense NM_001350887.1:c.302A>T NP_001337816.1:p.Asp101Val missense NM_001350889.1:c.302A>T NP_001337818.1:p.Asp101Val missense NM_001350893.1:c.302A>T NP_001337822.1:p.Asp101Val missense NM_001350894.1:c.302A>T NP_001337823.1:p.Asp101Val missense NM_001350895.1:c.269A>T NP_001337824.1:p.Asp90Val missense NM_022445.3:c.620A>T NM_022445.3:c.[620A>T] NR_146934.1:n.517A>T non-coding transcript variant NR_146935.1:n.656A>T non-coding transcript variant NR_146936.2:n.1075A>T non-coding transcript variant NC_000007.14:g.144453657T>A NC_000007.13:g.144150750T>A NG_032112.2:g.387397A>T - Protein change
- D101V, D158V, D202V, D207V, D90V
- Other names
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- Canonical SPDI
- NC_000007.14:144453656:T: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
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The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00000
The Genome Aggregation Database (gnomAD), exomes 0.00001
Exome Aggregation Consortium (ExAC) 0.00002
- 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 | ||
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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
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. |
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TPK1 | - | - |
GRCh38 GRCh38 GRCh37 |
292 | 349 |
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
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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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Uncertain significance (3) |
criteria provided, multiple submitters, no conflicts
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Oct 11, 2023 | RCV001354051.10 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jan 13, 2020 | RCV001751692.2 |
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
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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
(-)
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criteria provided, single submitter
Method: clinical testing
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Childhood encephalopathy due to thiamine pyrophosphokinase deficiency
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
inherited
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Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India
Accession: SCV001548567.2
First in ClinVar: Apr 13, 2021 Last updated: May 07, 2021 |
Sex: male
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Uncertain significance
(-)
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criteria provided, single submitter
Method: clinical testing
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Childhood encephalopathy due to thiamine pyrophosphokinase deficiency
Affected status: yes
Allele origin:
germline
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Neuberg Centre For Genomic Medicine, NCGM
Accession: SCV002073307.1
First in ClinVar: Feb 03, 2022 Last updated: Feb 03, 2022 |
Comment:
The missense variant p.D207V in TPK1 (NM_022445.4) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The … (more)
The missense variant p.D207V in TPK1 (NM_022445.4) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.D207V variant is observed in 2/18,388 (0.0109%) alleles from individuals of East Asian background in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. The p.D207V missense variant is predicted to be tolerated by both SIFT or PolyPhen2. The nucleotide c.620 in TPK1 is not conserved according to a GERP++ and PhyloP analysis of 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance. (less)
Clinical Features:
Developmental regression (present) , Dystonic disorder (present)
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Uncertain significance
(Jan 13, 2020)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV001997697.2
First in ClinVar: Nov 06, 2021 Last updated: Mar 04, 2023 |
Comment:
Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports … (more)
Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge (less)
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Uncertain significance
(Oct 11, 2023)
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criteria provided, single submitter
Method: clinical testing
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Childhood encephalopathy due to thiamine pyrophosphokinase deficiency
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV003827849.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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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 rs747262651 ...
HelpRecord last updated Apr 06, 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.