NM_006009.4(TUBA1A):c.1265G>A (p.Arg422His) AND Lissencephaly due to TUBA1A mutation

Germline classification:: Pathogenic (6 submissions)
Last evaluated:: Feb 8, 2013
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000007493.14

Allele description [Variation Report for NM_006009.4(TUBA1A):c.1265G>A (p.Arg422His)]

NM_006009.4(TUBA1A):c.1265G>A (p.Arg422His)

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.1265G>A (p.Arg422His)

HGVS:

NC_000012.12:g.49185101C>T
NG_008966.1:g.8978G>A
NM_001270399.2:c.1265G>A
NM_001270400.2:c.1160G>A
NM_006009.4:c.1265G>AMANE SELECT
NP_001257328.1:p.Arg422His
NP_001257329.1:p.Arg387His
NP_006000.2:p.Arg422His
NC_000012.11:g.49578884C>T
NM_006009.2:c.1265G>A
NM_006009.3:c.1265G>A

Protein change:

R387H; ARG422HIS

Links:

OMIM: 602529.0008; dbSNP: rs137853050

NCBI 1000 Genomes Browser:

rs137853050

Molecular consequence:

NM_001270399.2:c.1265G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001270400.2:c.1160G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_006009.4:c.1265G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000027693	OMIM	no assertion criteria provided	Pathogenic (Nov 1, 2008)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000195272	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2007)	Pathogenic (Feb 8, 2013)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000266414	GeneReviews	no classification provided	not provided	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 18728072, 20466733
SCV001432345	Service de Génétique Moléculaire, Hôpital Robert Debré	no assertion criteria provided	Pathogenic	unknown	clinical testing
SCV001451922	Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	de novo	research	PubMed (1) [See all records that cite this PMID]
SCV004037187	Institute for Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	germline	not provided	PubMed (1) [See all records that cite this PMID]

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing, literature only, not provided
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	unknown	yes	not provided	1	not provided	not provided	not provided	clinical testing
North Indian	de novo	yes	1	not provided	not provided	not provided	not provided	research

Citations

PubMed

Refining the phenotype of alpha-1a Tubulin (TUBA1A) mutation in patients with classical lissencephaly.

Morris-Rosendahl DJ, Najm J, Lachmeijer AM, Sztriha L, Martins M, Kuechler A, Haug V, Zeschnigk C, Martin P, Santos M, Vasconcelos C, Omran H, Kraus U, Van der Knaap MS, Schuierer G, Kutsche K, Uyanik G.

Clin Genet. 2008 Nov;74(5):425-33. doi: 10.1111/j.1399-0004.2008.01093.x.

PubMed [citation]

PMID:: 18954413

ACMG recommendations for standards for interpretation and reporting of sequence variations: Revisions 2007.

Richards CS, Bale S, Bellissimo DB, Das S, Grody WW, Hegde MR, Lyon E, Ward BE; Molecular Subcommittee of the ACMG Laboratory Quality Assurance Committee..

Genet Med. 2008 Apr;10(4):294-300. doi: 10.1097/GIM.0b013e31816b5cae.

PubMed [citation]

PMID:: 18414213

See all PubMed Citations (5)

Details of each submission

From OMIM, SCV000027693.3

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

Description

In 2 unrelated patients with lissencephaly-3 (LIS3; 611603), Morris-Rosendahl et al. (2008) identified a heterozygous 1265G-A transition in exon 4 of the TUBA1A gene, resulting in an arg422-to-his (R422H) substitution. In addition to the classic features of microcephaly, seizure, pachygyria, and hypoplasia of the corpus callosum and cerebellum, both patients had subtle evidence of subcortical band heterotopia.

#	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

From Genetic Services Laboratory, University of Chicago, SCV000195272.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

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

From GeneReviews, SCV000266414.2

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

Description

Classic lissencephaly

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

From Service de Génétique Moléculaire, Hôpital Robert Debré, SCV001432345.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

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

From Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, SCV001451922.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	North Indian	1	not provided	not provided	research	PubMed (1)

Description

Analysis of the exome sequencing data showed a heterozygous sequence variant in TUBA1A gene. This variant is predicted as Disease Causing by MutationTaster. Sanger sequencing confirmed the variation in the proband. Parents were homozygous for the wildtype allele.

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

From Institute for Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin, SCV004037187.1

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

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

Last Updated: Feb 14, 2024

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