NM_178012.5(TUBB2B):c.514T>C (p.Ser172Pro) AND Complex cortical dysplasia with other brain malformations 7

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 1, 2009
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000000454.5

Allele description [Variation Report for NM_178012.5(TUBB2B):c.514T>C (p.Ser172Pro)]

NM_178012.5(TUBB2B):c.514T>C (p.Ser172Pro)

Gene:

TUBB2B:tubulin beta 2B class IIb [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p25.2

Genomic location:

Preferred name:

NM_178012.5(TUBB2B):c.514T>C (p.Ser172Pro)

HGVS:

NC_000006.12:g.3225575A>G
NG_016715.1:g.7160T>C
NM_178012.5:c.514T>CMANE SELECT
NP_821080.1:p.Ser172Pro
NC_000006.11:g.3225809A>G
Q9BVA1:p.Ser172Pro

Protein change:

S172P; SER172PRO

Links:

UniProtKB: Q9BVA1#VAR_063389; OMIM: 612850.0001; dbSNP: rs137853194

NCBI 1000 Genomes Browser:

rs137853194

Molecular consequence:

NM_178012.5:c.514T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Complex cortical dysplasia with other brain malformations 7
Synonyms:: Polymicrogyria, asymmetric
Identifiers:: MONDO: MONDO:0012399; MedGen: C3552236; Orphanet: 300573; OMIM: 610031

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000020603	OMIM	no assertion criteria provided	Pathogenic (Jun 1, 2009)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 19465910, 25059107

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000020603

OMIM

no assertion criteria provided

Pathogenic
(Jun 1, 2009)

germline

literature only

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Mutations in the beta-tubulin gene TUBB2B result in asymmetrical polymicrogyria.

Jaglin XH, Poirier K, Saillour Y, Buhler E, Tian G, Bahi-Buisson N, Fallet-Bianco C, Phan-Dinh-Tuy F, Kong XP, Bomont P, Castelnau-Ptakhine L, Odent S, Loget P, Kossorotoff M, Snoeck I, Plessis G, Parent P, Beldjord C, Cardoso C, Represa A, Flint J, Keays DA, et al.

Nat Genet. 2009 Jun;41(6):746-52. doi: 10.1038/ng.380. Epub 2009 May 24.

PubMed [citation]

PMID:: 19465910
PMCID:: PMC2883584

Mutations in tubulin genes are frequent causes of various foetal malformations of cortical development including microlissencephaly.

Fallet-Bianco C, Laquerrière A, Poirier K, Razavi F, Guimiot F, Dias P, Loeuillet L, Lascelles K, Beldjord C, Carion N, Toussaint A, Revencu N, Addor MC, Lhermitte B, Gonzales M, Martinovich J, Bessieres B, Marcy-Bonnière M, Jossic F, Marcorelles P, Loget P, Chelly J, et al.

Acta Neuropathol Commun. 2014 Jul 25;2:69. doi: 10.1186/2051-5960-2-69.

PubMed [citation]

PMID:: 25059107
PMCID:: PMC4222268

Details of each submission

From OMIM, SCV000020603.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

Description

In a 27-week-old male fetus with complex cortical dysplasia with other brain malformations-7 (CDCBM7; 610031), Jaglin et al. (2009) identified a heterozygous 514T-C transition in the TUBB2B gene, resulting in a ser172-to-pro (S172P) substitution. Postmortem examination showed bilateral and asymmetric frontotemporal polymicrogyria with heterotopic neuronal cells in the cerebellum and agenesis of the corpus callosum. In vitro functional expression studies showed that the S172P-mutant protein was unable to form a functional alpha/beta-tubulin heterodimer with little evidence of incorporation into well-defined microtubules.

Fallet-Bianco et al. (2014) identified a heterozygous S172P mutation in a fetus (individual 12) with microcephaly, polymicrogyria, focal neuronoglial overmigration, heterotopic neurons, complete agenesis of the corpus callosum, and mild cerebellar hypoplasia. Functional studies of the variant and studies of patient cells were not performed.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 23, 2022

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