ClinVar Genomic variation as it relates to human health
NM_006009.4(TUBA1A):c.790C>T (p.Arg264Cys)
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_006009.4(TUBA1A):c.790C>T (p.Arg264Cys)
Variation ID: 7070 Accession: VCV000007070.18
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 12q13.12 12: 49185576 (GRCh38) [ NCBI UCSC ] 12: 49579359 (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 4, 2013 Mar 5, 2024 Oct 4, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_006009.4:c.790C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_006000.2:p.Arg264Cys missense NM_001270399.2:c.790C>T NP_001257328.1:p.Arg264Cys missense NM_001270400.2:c.685C>T NP_001257329.1:p.Arg229Cys missense NC_000012.12:g.49185576G>A NC_000012.11:g.49579359G>A NG_008966.1:g.8503C>T Q71U36:p.Arg264Cys - Protein change
- R264C, R229C
- Other names
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- Canonical SPDI
- NC_000012.12:49185575: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
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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
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
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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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TUBA1A | No evidence available | No evidence available |
GRCh38 GRCh37 |
354 | 365 |
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
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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 (6) |
criteria provided, multiple submitters, no conflicts
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Oct 4, 2022 | RCV000007486.14 | |
Pathogenic (1) |
criteria provided, single submitter
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Sep 16, 2016 | RCV000622693.3 | |
Pathogenic (1) |
criteria provided, single submitter
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Jul 1, 2018 | RCV000767404.2 | |
Pathogenic (1) |
criteria provided, single submitter
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Apr 15, 2021 | RCV001564937.4 | |
Likely pathogenic (1) |
no assertion criteria provided
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- | RCV001291302.2 |
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
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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Pathogenic
(Jul 07, 2014)
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criteria provided, single submitter
Method: clinical testing
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Lissencephaly 3
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV000195291.1
First in ClinVar: Nov 23, 2014 Last updated: Nov 23, 2014 |
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Pathogenic
(Jul 01, 2018)
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criteria provided, single submitter
Method: literature only
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Tubulinopathies
Affected status: yes
Allele origin:
de novo
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Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg
Accession: SCV000898019.1
First in ClinVar: Apr 21, 2019 Last updated: Apr 21, 2019 |
Comment:
A variant that is classified as pathogenic has been identified in the TUBA1A gene in a 2 years old born individual of male sex. The … (more)
A variant that is classified as pathogenic has been identified in the TUBA1A gene in a 2 years old born individual of male sex. The c.790C>T, p.(Arg264Cys) variant has been reported as a variant of de novo origin. This variant and associated phenotype was previously reported by Keays et al. Cell, 2007 PMID: 17218254. HPO-standardized clinical features were: Partial agenesis of the corpus callosum (HP:0001338); Pachygyria (HP:0001302); Dysgenesis of the cerebellar vermis (HP:0002195); Hypoplasia of the brainstem (HP:0002365); Dilation of lateral ventricles (HP:0006956); Gray matter heterotopia (HP:0002281); Congenital microcephaly (HP:0011451); Microcephaly (HP:0000252); no Seizures (-HP:0001250) (less)
Number of individuals with the variant: 10
Age: 0-9 years
Sex: male
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Pathogenic
(Apr 15, 2021)
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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: SCV001788183.1
First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021 |
Comment:
Published functional studies demonstrate a damaging effect as alpha tubulin protein harboring R264C has a diminished capacity of de novo tubulin heterodimer formation (Tian et … (more)
Published functional studies demonstrate a damaging effect as alpha tubulin protein harboring R264C has a diminished capacity of de novo tubulin heterodimer formation (Tian et al., 2008); Not observed in large population cohorts (Lek et al., 2016); Missense variants in this gene are often considered pathogenic (Stenson et al., 2014); This variant is associated with the following publications: (PMID: 29671837, 28677066, 17584854, 17218254, 18199681, 18669490, 27431206, 18728072) (less)
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Pathogenic
(Oct 04, 2022)
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criteria provided, single submitter
Method: clinical testing
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Lissencephaly due to TUBA1A mutation
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
de novo
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Genetics Laboratory, UDIAT-Centre Diagnòstic, Hospital Universitari Parc Tauli
Accession: SCV002577725.1
First in ClinVar: Oct 08, 2022 Last updated: Oct 08, 2022 |
Comment:
PS4;PM1;PM2_supporting;PM5;PP2;PP3
Clinical Features:
Abnormal corpus callosum morphology (present) , Microcephaly (present) , Polymicrogyria (present) , Abnormal facial shape (present) , Global developmental delay (present)
Sex: female
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Pathogenic
(Sep 16, 2016)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: yes
Allele origin:
germline
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Ambry Genetics
Accession: SCV000741808.3
First in ClinVar: Apr 15, 2018 Last updated: Jan 07, 2023 |
Number of individuals with the variant: 1
Clinical Features:
Congenital microcephaly (present) , Neurodevelopmental delay (present) , Cerebellar atrophy (present) , Coarse facial features (present) , Muscular hypotonia (present) , Hypertonia (present) , Spasticity … (more)
Congenital microcephaly (present) , Neurodevelopmental delay (present) , Cerebellar atrophy (present) , Coarse facial features (present) , Muscular hypotonia (present) , Hypertonia (present) , Spasticity (present) , Hyperreflexia (present) , Congenital cerebellar hypoplasia (present) , Ventriculomegaly (present) , Abnormality of eye movement (present) (less)
Sex: male
Ethnicity/Population group: Russian/Polish/Hungarian
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Lissencephaly due to TUBA1A mutation
Affected status: yes
Allele origin:
de novo
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Molecular Genetics Lab, CHRU Brest
Accession: SCV004697781.1
First in ClinVar: Mar 05, 2024 Last updated: Mar 05, 2024 |
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Pathogenic
(Oct 01, 2008)
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no assertion criteria provided
Method: literature only
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LISSENCEPHALY 3
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000027686.2
First in ClinVar: Apr 04, 2013 Last updated: Jun 09, 2019 |
Comment on evidence:
In a patient with lissencephaly (LIS3; 611603), Keays et al. (2007) and Poirier et al. (2007) identified a heterozygous de novo 790C-T transition in exon … (more)
In a patient with lissencephaly (LIS3; 611603), Keays et al. (2007) and Poirier et al. (2007) identified a heterozygous de novo 790C-T transition in exon 4 of the TUBA1A gene, resulting in an arg264-to-cys (R264C) substitution in a loop between H8 and S7. The patient had microcephaly, pachygyria, an abnormally shaped corpus callosum, and hypoplasia of the cerebellar vermis and brainstem. Clinical features included severe mental retardation, mild motor delay, and absence of seizures. Poirier et al. (2007) reported another unrelated patient with a similar phenotype who carried the R264C mutation. Bahi-Buisson et al. (2008) identified the R264C mutation in 2 additional unrelated patients with LIS3. (less)
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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Lissencephaly due to TUBA1A mutation
Affected status: yes
Allele origin:
unknown
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Service de Génétique Moléculaire, Hôpital Robert Debré
Accession: SCV001432379.1
First in ClinVar: Sep 19, 2020 Last updated: Sep 19, 2020 |
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Likely pathogenic
(-)
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no assertion criteria provided
Method: research
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lissencephaly
Affected status: yes
Allele origin:
unknown
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University of Washington Center for Mendelian Genomics, University of Washington
Accession: SCV001479774.1
First in ClinVar: Feb 20, 2021 Last updated: Feb 20, 2021 |
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not provided
(-)
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no classification provided
Method: literature only
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Lissencephaly type 3
Affected status: yes
Allele origin:
germline
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GeneReviews
Accession: SCV000266415.2
First in ClinVar: Mar 29, 2016 Last updated: Oct 01, 2022 |
Comment:
Polymicrogyria-like cortical dysplasia
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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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Tubulinopathies Overview. | Adam MP | - | 2021 | PMID: 27010057 |
The mutational and phenotypic spectrum of TUBA1A-associated tubulinopathy. | Hebebrand M | Orphanet journal of rare diseases | 2019 | PMID: 30744660 |
Analysis of 17 genes detects mutations in 81% of 811 patients with lissencephaly. | Di Donato N | Genetics in medicine : official journal of the American College of Medical Genetics | 2018 | PMID: 29671837 |
Clinical, genetic and neuropathological findings in a series of 138 fetuses with a corpus callosum malformation. | Alby C | Birth defects research. Part A, Clinical and molecular teratology | 2016 | PMID: 26663670 |
The wide spectrum of tubulinopathies: what are the key features for the diagnosis? | Bahi-Buisson N | Brain : a journal of neurology | 2014 | PMID: 24860126 |
Refinement of cortical dysgeneses spectrum associated with TUBA1A mutations. | Bahi-Buisson N | Journal of medical genetics | 2008 | PMID: 18728072 |
Large spectrum of lissencephaly and pachygyria phenotypes resulting from de novo missense mutations in tubulin alpha 1A (TUBA1A). | Poirier K | Human mutation | 2007 | PMID: 17584854 |
Mutations in alpha-tubulin cause abnormal neuronal migration in mice and lissencephaly in humans. | Keays DA | Cell | 2007 | PMID: 17218254 |
Text-mined citations for rs137853043 ...
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.