NM_006009.4(TUBA1A):c.518C>T (p.Pro173Leu) AND Inborn genetic diseases

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 9, 2021
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:: RCV002536596.2

Allele description [Variation Report for NM_006009.4(TUBA1A):c.518C>T (p.Pro173Leu)]

NM_006009.4(TUBA1A):c.518C>T (p.Pro173Leu)

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.518C>T (p.Pro173Leu)

HGVS:

NC_000012.12:g.49185848G>A
NG_008966.1:g.8231C>T
NM_001270399.2:c.518C>T
NM_001270400.2:c.413C>T
NM_006009.4:c.518C>TMANE SELECT
NP_001257328.1:p.Pro173Leu
NP_001257329.1:p.Pro138Leu
NP_006000.2:p.Pro173Leu
NC_000012.11:g.49579631G>A
NM_001270399.1:c.518C>T
NM_006009.2:c.518C>T
NM_006009.3:c.518C>T

Protein change:

P138L

Links:

dbSNP: rs1565627304

NCBI 1000 Genomes Browser:

rs1565627304

Molecular consequence:

NM_001270399.2:c.518C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001270400.2:c.413C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_006009.4:c.518C>T - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

dominant_negative_variant [Sequence Ontology: SO:0002052]

Condition(s)

Name:: Inborn genetic diseases
Identifiers:: MeSH: D030342; MedGen: C0950123

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003706329	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Nov 9, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 24860126, 30744660 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003706329

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Nov 9, 2021)

germline

clinical testing

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

Citation Link

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

The wide spectrum of tubulinopathies: what are the key features for the diagnosis?

Bahi-Buisson N, Poirier K, Fourniol F, Saillour Y, Valence S, Lebrun N, Hully M, Bianco CF, Boddaert N, Elie C, Lascelles K, Souville I; LIS-Tubulinopathies Consortium, Beldjord C, Chelly J.

Brain. 2014 Jun;137(Pt 6):1676-700. doi: 10.1093/brain/awu082.

PubMed [citation]

PMID:: 24860126

The mutational and phenotypic spectrum of TUBA1A-associated tubulinopathy.

Hebebrand M, Hüffmeier U, Trollmann R, Hehr U, Uebe S, Ekici AB, Kraus C, Krumbiegel M, Reis A, Thiel CT, Popp B.

Orphanet J Rare Dis. 2019 Feb 11;14(1):38. doi: 10.1186/s13023-019-1020-x. Review.

PubMed [citation]

PMID:: 30744660
PMCID:: PMC6371496

Details of each submission

From Ambry Genetics, SCV003706329.2

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

Description

The c.518C>T (p.P173L) alteration is located in exon 4 (coding exon 4) of the TUBA1A gene. This alteration results from a C to T substitution at nucleotide position 518, causing the proline (P) at amino acid position 173 to be replaced by a leucine (L). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This alteration has been reported de novo in multiple unrelated patients with global developmental delay, cortical and subcortical malformations, microcephaly, spasticity, and epilepsy (Bahi-Buisson, 2014; Hebebrand, 2019; DECIPHER). This amino acid position is highly conserved in available vertebrate species. This missense alteration is located in a region that has a low rate of benign missense variation (Lek, 2016; Firth, 2009). This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as pathogenic.

#	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: Sep 29, 2024

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