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NM_006009.4(TUBA1A):c.562A>C (p.Ile188Leu) AND Lissencephaly due to TUBA1A mutation

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 15, 2010
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:
RCV000007488.4

Allele description [Variation Report for NM_006009.4(TUBA1A):c.562A>C (p.Ile188Leu)]

NM_006009.4(TUBA1A):c.562A>C (p.Ile188Leu)

Gene:
TUBA1A:tubulin alpha 1a [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
12q13.12
Genomic location:
Preferred name:
NM_006009.4(TUBA1A):c.562A>C (p.Ile188Leu)
HGVS:
  • NC_000012.12:g.49185804T>G
  • NG_008966.1:g.8275A>C
  • NM_001270399.2:c.562A>C
  • NM_001270400.2:c.457A>C
  • NM_006009.4:c.562A>CMANE SELECT
  • NP_001257328.1:p.Ile188Leu
  • NP_001257329.1:p.Ile153Leu
  • NP_006000.2:p.Ile188Leu
  • NC_000012.11:g.49579587T>G
  • NM_006009.3:c.562A>C
  • Q71U36:p.Ile188Leu
Protein change:
I153L; ILE188LEU
Links:
UniProtKB: Q71U36#VAR_039332; OMIM: 602529.0003; dbSNP: rs137853045
NCBI 1000 Genomes Browser:
rs137853045
Molecular consequence:
  • NM_001270399.2:c.562A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001270400.2:c.457A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_006009.4:c.562A>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Lissencephaly due to TUBA1A mutation (LIS3)
Synonyms:
Lissencephaly 3
Identifiers:
MONDO: MONDO:0012703; MedGen: C4305153; Orphanet: 171680; OMIM: 611603

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000027688OMIM
no assertion criteria provided
Pathogenic
(Sep 15, 2010) 		germlineliterature only

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Large spectrum of lissencephaly and pachygyria phenotypes resulting from de novo missense mutations in tubulin alpha 1A (TUBA1A).

Poirier K, Keays DA, Francis F, Saillour Y, Bahi N, Manouvrier S, Fallet-Bianco C, Pasquier L, Toutain A, Tuy FP, Bienvenu T, Joriot S, Odent S, Ville D, Desguerre I, Goldenberg A, Moutard ML, Fryns JP, van Esch H, Harvey RJ, Siebold C, Flint J, et al.

Hum Mutat. 2007 Nov;28(11):1055-64.

PubMed [citation]
PMID:
17584854

Disease-associated mutations in TUBA1A result in a spectrum of defects in the tubulin folding and heterodimer assembly pathway.

Tian G, Jaglin XH, Keays DA, Francis F, Chelly J, Cowan NJ.

Hum Mol Genet. 2010 Sep 15;19(18):3599-613. doi: 10.1093/hmg/ddq276. Epub 2010 Jul 5.

PubMed [citation]
PMID:
20603323
PMCID:
PMC2928131

Details of each submission

From OMIM, SCV000027688.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

In a female patient with lissencephaly-3 (LIS3; 611603), Poirier et al. (2007) identified a heterozygous de novo 562A-C transversion in the TUBA1A gene, resulting in an ile188-to-leu (I188L) substitution. She had microcephaly, laminar heterotopia, thin corpus callosum with partial agenesis, and hypoplasia of the brainstem and cerebellar vermis.

By extensive in vitro functional expression assays, Tian et al. (2010) found that mutant I188L performed like wildtype, although there was a slight reduction in the amount of protein translated and a slight reduction in the formation of tubulin assembly intermediates. There were no obvious effects on de novo heterodimer assembly or microtubule dynamics, suggesting that the disease phenotype is likely to be caused by an effect on other microtubule-dependent processes such as the binding of associated proteins.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 23, 2024