NM_006009.4(TUBA1A):c.217A>G (p.Thr73Ala) AND Lissencephaly due to TUBA1A mutation

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jun 18, 2019
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000850184.1

Allele description [Variation Report for NM_006009.4(TUBA1A):c.217A>G (p.Thr73Ala)]

NM_006009.4(TUBA1A):c.217A>G (p.Thr73Ala)

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.217A>G (p.Thr73Ala)

HGVS:

NC_000012.12:g.49186620T>C
NG_008966.1:g.7459A>G
NM_001270399.2:c.217A>G
NM_001270400.2:c.112A>G
NM_006009.4:c.217A>GMANE SELECT
NP_001257328.1:p.Thr73Ala
NP_001257329.1:p.Thr38Ala
NP_006000.2:p.Thr73Ala
NC_000012.11:g.49580403T>C

Protein change:

T38A

Links:

dbSNP: rs1592260393

NCBI 1000 Genomes Browser:

rs1592260393

Molecular consequence:

NM_001270399.2:c.217A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001270400.2:c.112A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_006009.4:c.217A>G - 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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000992381	Johns Hopkins Genomics, Johns Hopkins University	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jun 18, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000992381

Johns Hopkins Genomics, Johns Hopkins University

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jun 18, 2019)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Johns Hopkins Genomics, Johns Hopkins University, SCV000992381.1

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

Description

This TUBA1A variant is absent from large population datasets and TUBA1A missense variation appears to be extremely uncommon in these populations (gnomAD expected number of missense variants: 260.7, observed number of missense variants: 7, Z=5.58). This variant has not been reported in the literature, to our knowledge. Of two bioinformatics tools queried, one predicts that the substitution would be damaging, while the second predicts that it would be tolerated. The threonine residue at this position is evolutionarily conserved across all higher order mammals and nearly all other species assessed. Due to the apparently de novo state of this variant, the absence of this missense change from healthy population sets, and correlation with the patients clinical presentation, c.217A>G is likely pathogenic in this patient.

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

Last Updated: Dec 2, 2023

ClinVar

Relating variation to medicine