The c.743C>T (p.A248V) alteration is located in exon 4 (coding exon 4) of the TUBB2A gene. This alteration results from a C to T substitution at nucleotide position 743, causing the alanine (A) at amino acid position 248 to be replaced by a valine (V). Based on data from the Genome Aggregation Database (gnomAD) database, the TUBB2A c.743C>T alteration was observed in 0.03% (87/252926) of total alleles studied, with a frequency of 0.37% (68/18432) in the African subpopulation; however, this data may be an unreliable mismapping artefact (Ragoussis, 2021). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
ClinVar Genomic variation as it relates to human health
NM_001069.3(TUBB2A):c.743C>T (p.Ala248Val)
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.
(13)
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.
Conflicting classifications of pathogenicity
Pathogenic(7); Likely pathogenic(2); Uncertain significance(2); Likely benign(1)
Pathogenic(7); Likely pathogenic(2); Uncertain significance(2); Likely benign(1)
13
criteria provided, conflicting classifications
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_001069.3(TUBB2A):c.743C>T (p.Ala248Val)
Variation ID: 127101 Accession: VCV000127101.23
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 6p25.2 6: 3154458 (GRCh38) [ NCBI UCSC ] 6: 3154692 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 27, 2014 Jul 23, 2024 Apr 4, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001069.3:c.743C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001060.1:p.Ala248Val missense NM_001310315.2:c.488C>T NP_001297244.1:p.Ala163Val missense NC_000006.12:g.3154458G>A NC_000006.11:g.3154692G>A NG_042223.1:g.8092C>T Q13885:p.Ala248Val - Protein change
- A248V, A163V
- Other names
- -
- Canonical SPDI
- NC_000006.12:3154457:G:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
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.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
The Genome Aggregation Database (gnomAD), exomes 0.00003
Exome Aggregation Consortium (ExAC) 0.00026
- 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. |
|||
| TUBB2A | - | - |
GRCh38 GRCh37 |
297 | 376 | |
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. |
|---|---|---|---|---|
| Conflicting interpretations of pathogenicity (8) |
criteria provided, conflicting classifications
|
Apr 4, 2024 | RCV000114959.21 | |
| Likely benign (1) |
criteria provided, single submitter
|
Apr 14, 2015 | RCV000202934.1 | |
| Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
Oct 5, 2023 | RCV000254754.11 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Apr 28, 2021 | RCV002514574.2 |
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. |
|
|---|---|---|---|---|---|
|
Uncertain significance
(Apr 04, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Complex cortical dysplasia with other brain malformations 5
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
Accession: SCV004810032.1
First in ClinVar: Apr 15, 2024 Last updated: Apr 15, 2024 |
|
|
|
Uncertain significance
(Apr 28, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV003685323.2
First in ClinVar: Feb 07, 2023 Last updated: May 01, 2024 |
Comment:
The c.743C>T (p.A248V) alteration is located in exon 4 (coding exon 4) of the TUBB2A gene. This alteration results from a C to T substitution … (more)
The c.743C>T (p.A248V) alteration is located in exon 4 (coding exon 4) of the TUBB2A gene. This alteration results from a C to T substitution at nucleotide position 743, causing the alanine (A) at amino acid position 248 to be replaced by a valine (V). Based on data from the Genome Aggregation Database (gnomAD) database, the TUBB2A c.743C>T alteration was observed in 0.03% (87/252926) of total alleles studied, with a frequency of 0.37% (68/18432) in the African subpopulation; however, this data may be an unreliable mismapping artefact (Ragoussis, 2021). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. (less)
|
|
|
Likely benign
(Apr 14, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
unknown
|
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia
Accession: SCV000257767.2
First in ClinVar: Dec 27, 2015 Last updated: Dec 27, 2015 |
|
|
|
Pathogenic
(Jun 11, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Complex cortical dysplasia with other brain malformations 5
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
de novo
|
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München
Accession: SCV001149975.1
First in ClinVar: Feb 03, 2020 Last updated: Feb 03, 2020 |
Sex: male
Tissue: blood
|
|
|
Pathogenic
(Nov 25, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Complex cortical dysplasia with other brain malformations 5
Affected status: yes
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV001525134.1
First in ClinVar: Mar 22, 2021 Last updated: Mar 22, 2021 |
Comment:
This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
|
|
|
Likely pathogenic
(Dec 08, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Complex cortical dysplasia with other brain malformations 5
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV002759375.2
First in ClinVar: Dec 11, 2022 Last updated: May 27, 2023 |
Clinical Features:
Aggressive behavior (present) , Delayed speech and language development (present) , Secondary hyperparathyroidism (present) , Seizure (present) , Global developmental delay (present) , Gait ataxia … (more)
Aggressive behavior (present) , Delayed speech and language development (present) , Secondary hyperparathyroidism (present) , Seizure (present) , Global developmental delay (present) , Gait ataxia (present) , Hypocalcemia (present) , Prolonged QTc interval (present) , Dystonic gait (present) , Decreased circulating vitamin D concentration (present) (less)
|
|
|
Pathogenic
(Oct 05, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV003262008.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 248 of the TUBB2A protein (p.Ala248Val). … (more)
This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 248 of the TUBB2A protein (p.Ala248Val). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with TUBB2A-related conditions (PMID: 24702957, 27770045, 32203252, 32571897; Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 127101). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on TUBB2A protein function. Experimental studies have shown that this missense change affects TUBB2A function (PMID: 24702957, 29547997). For these reasons, this variant has been classified as Pathogenic. (less)
|
|
|
Likely pathogenic
(Jan 01, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Complex cortical dysplasia with other brain malformations 5
Affected status: yes
Allele origin:
de novo
|
NeuroMeGen, Hospital Clinico Santiago de Compostela
Accession: SCV000693794.1
First in ClinVar: Oct 11, 2015 Last updated: Oct 11, 2015 |
|
|
|
Pathogenic
(May 27, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Complex cortical dysplasia with other brain malformations 5
Affected status: unknown
Allele origin:
unknown
|
Mendelics
Accession: SCV001137048.2
First in ClinVar: Jan 09, 2020 Last updated: Jun 05, 2022 |
|
|
|
Pathogenic
(Oct 27, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000321988.9
First in ClinVar: Oct 09, 2016 Last updated: Mar 04, 2023 |
Comment:
Published functional studies demonstrate that this variant has a reduced rate of heterodimer incorporation into the in vitro cytoskeleton network in comparison with wild type-expressing … (more)
Published functional studies demonstrate that this variant has a reduced rate of heterodimer incorporation into the in vitro cytoskeleton network in comparison with wild type-expressing cells (Cushion et al., 2014); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 26934450, 24702957, 27770045, 32203252, 32571897) (less)
|
|
|
Pathogenic
(Nov 03, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: not provided
Allele origin:
germline
|
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden
Accession: SCV002011190.3
First in ClinVar: Nov 06, 2021 Last updated: Jul 16, 2023 |
|
|
|
Pathogenic
(Jul 17, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Complex cortical dysplasia with other brain malformations 5
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV005086144.1
First in ClinVar: Jul 23, 2024 Last updated: Jul 23, 2024 |
Comment:
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0104 - Dominant negative is a likely mechanism of … (more)
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0104 - Dominant negative is a likely mechanism of disease in this gene and is associated with cortical dysplasia, complex, with other brain malformations 5, (MIM#615763). Functional studies have shown missense variants to cause weakened incorporation into cytoskeleton, and potentially impaired heterodimer formation indicating loss of function. However, the mutational spectrum is more suggestive of a dominant negative mechanism (PMID: 24702957). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from alanine to valine. (I) 0251 - This variant is heterozygous. (I) 0302 - Variant is present in gnomAD (v3) <0.001 for a dominant condition (400 heterozygotes, 0 homozygotes). However, most of these are likely sequencing artefacts. The remaining were observed in individuals with a neurodevelopmental disorder (PMID: 33547136). (SP) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (v3) (1 heterozygote, 0 homozygotes). (I) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0603 - Missense variant in a region that is highly intolerant to missense variation (high constraint region in DECIPHER). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been reported once each as a VUS and likely benign; however, the majority of submissions are pathogenic and likely pathogenic (ClinVar). It has also been observed multiple times as de novo in individuals with simplified gyral patterning and infantile-onset epilepsy (PMID: 24702957, PMID: 32203252). (SP) 1203 - This variant has been shown to be de novo in the proband (parental status confirmed, by trio analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign (less)
|
|
|
Pathogenic
(Apr 03, 2014)
|
no assertion criteria provided
Method: literature only
|
CORTICAL DYSPLASIA, COMPLEX, WITH OTHER BRAIN MALFORMATIONS 5
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000148869.2
First in ClinVar: Apr 27, 2014 Last updated: Sep 25, 2021 |
Comment on evidence:
In a girl with complex cortical dysplasia with other brain malformations-5 (CDCBM5; 615763), Cushion et al. (2014) identified a de novo heterozygous c.743C-T transition in … (more)
In a girl with complex cortical dysplasia with other brain malformations-5 (CDCBM5; 615763), Cushion et al. (2014) identified a de novo heterozygous c.743C-T transition in the TUBB2A gene, resulting in an ala248-to-val (A248V) substitution at a highly conserved residue in a loop at the intradimer interface that is a critical GTP-binding site for microtubule polymerization. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the dbSNP, 1000 Genomes Project, or Exome Variant Server databases. The A248V mutant protein decreased incorporation into the in vitro cytoskeleton network compared to wildtype, with more of the mutant protein remaining unpolymerized in the cytoplasm. These findings correlated with the less severe brain malformations seen in this child compared to those in a child with a different TUBB2A mutation (N247K; 615101.0001). In a 4-year-old patient with CDCBM5, Rodan et al. (2017) identified heterozygosity for the A248V mutation in the TUBB2A gene. The de novo mutation was identified by trio whole-exome sequencing. The mutation was not present in the ExAC database. Functional studies were not performed. (less)
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Comment:
Comment:
This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Comment:
This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 248 of the TUBB2A protein (p.Ala248Val). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with TUBB2A-related conditions (PMID: 24702957, 27770045, 32203252, 32571897; Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 127101). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on TUBB2A protein function. Experimental studies have shown that this missense change affects TUBB2A function (PMID: 24702957, 29547997). For these reasons, this variant has been classified as Pathogenic.
Comment:
Published functional studies demonstrate that this variant has a reduced rate of heterodimer incorporation into the in vitro cytoskeleton network in comparison with wild type-expressing cells (Cushion et al., 2014); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 26934450, 24702957, 27770045, 32203252, 32571897)
Comment:
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0104 - Dominant negative is a likely mechanism of disease in this gene and is associated with cortical dysplasia, complex, with other brain malformations 5, (MIM#615763). Functional studies have shown missense variants to cause weakened incorporation into cytoskeleton, and potentially impaired heterodimer formation indicating loss of function. However, the mutational spectrum is more suggestive of a dominant negative mechanism (PMID: 24702957). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from alanine to valine. (I) 0251 - This variant is heterozygous. (I) 0302 - Variant is present in gnomAD (v3) <0.001 for a dominant condition (400 heterozygotes, 0 homozygotes). However, most of these are likely sequencing artefacts. The remaining were observed in individuals with a neurodevelopmental disorder (PMID: 33547136). (SP) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (v3) (1 heterozygote, 0 homozygotes). (I) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0603 - Missense variant in a region that is highly intolerant to missense variation (high constraint region in DECIPHER). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been reported once each as a VUS and likely benign; however, the majority of submissions are pathogenic and likely pathogenic (ClinVar). It has also been observed multiple times as de novo in individuals with simplified gyral patterning and infantile-onset epilepsy (PMID: 24702957, PMID: 32203252). (SP) 1203 - This variant has been shown to be de novo in the proband (parental status confirmed, by trio analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
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 c.743C>T (p.A248V) alteration is located in exon 4 (coding exon 4) of the TUBB2A gene. This alteration results from a C to T substitution at nucleotide position 743, causing the alanine (A) at amino acid position 248 to be replaced by a valine (V). Based on data from the Genome Aggregation Database (gnomAD) database, the TUBB2A c.743C>T alteration was observed in 0.03% (87/252926) of total alleles studied, with a frequency of 0.37% (68/18432) in the African subpopulation; however, this data may be an unreliable mismapping artefact (Ragoussis, 2021). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Comment:
This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Comment:
This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 248 of the TUBB2A protein (p.Ala248Val). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with TUBB2A-related conditions (PMID: 24702957, 27770045, 32203252, 32571897; Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 127101). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on TUBB2A protein function. Experimental studies have shown that this missense change affects TUBB2A function (PMID: 24702957, 29547997). For these reasons, this variant has been classified as Pathogenic.
Comment:
Published functional studies demonstrate that this variant has a reduced rate of heterodimer incorporation into the in vitro cytoskeleton network in comparison with wild type-expressing cells (Cushion et al., 2014); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 26934450, 24702957, 27770045, 32203252, 32571897)
Comment:
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0104 - Dominant negative is a likely mechanism of disease in this gene and is associated with cortical dysplasia, complex, with other brain malformations 5, (MIM#615763). Functional studies have shown missense variants to cause weakened incorporation into cytoskeleton, and potentially impaired heterodimer formation indicating loss of function. However, the mutational spectrum is more suggestive of a dominant negative mechanism (PMID: 24702957). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from alanine to valine. (I) 0251 - This variant is heterozygous. (I) 0302 - Variant is present in gnomAD (v3) <0.001 for a dominant condition (400 heterozygotes, 0 homozygotes). However, most of these are likely sequencing artefacts. The remaining were observed in individuals with a neurodevelopmental disorder (PMID: 33547136). (SP) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (v3) (1 heterozygote, 0 homozygotes). (I) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0603 - Missense variant in a region that is highly intolerant to missense variation (high constraint region in DECIPHER). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been reported once each as a VUS and likely benign; however, the majority of submissions are pathogenic and likely pathogenic (ClinVar). It has also been observed multiple times as de novo in individuals with simplified gyral patterning and infantile-onset epilepsy (PMID: 24702957, PMID: 32203252). (SP) 1203 - This variant has been shown to be de novo in the proband (parental status confirmed, by trio analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Using data from the 100,000 Genomes Project to resolve conflicting interpretations of a recurrent TUBB2A mutation. | Ragoussis V | Journal of medical genetics | 2022 | PMID: 33547136 |
| Defining the phenotypical spectrum associated with variants in TUBB2A. | Brock S | Journal of medical genetics | 2021 | PMID: 32571897 |
| De novo mutations of TUBB2A cause infantile-onset epilepsy and developmental delay. | Cai S | Journal of human genetics | 2020 | PMID: 32203252 |
| Defective kinesin binding of TUBB2A causes progressive spastic ataxia syndrome resembling sacsinopathy. | Sferra A | Human molecular genetics | 2018 | PMID: 29547997 |
| De novo pathogenic variant in TUBB2A presenting with arthrogryposis multiplex congenita, brain abnormalities, and severe developmental delay. | Ejaz R | American journal of medical genetics. Part A | 2017 | PMID: 28840640 |
| De Novo TUBB2A Variant Presenting With Anterior Temporal Pachygyria. | Rodan LH | Journal of child neurology | 2017 | PMID: 27770045 |
| De novo mutations in the beta-tubulin gene TUBB2A cause simplified gyral patterning and infantile-onset epilepsy. | Cushion TD | American journal of human genetics | 2014 | PMID: 24702957 |
Text-mined citations for rs2808001 ...
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.