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NM_006086.4(TUBB3):c.1228G>A (p.Glu410Lys) AND TUBB3-related disorder

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 10, 2023
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:
RCV004547462.1

Allele description [Variation Report for NM_006086.4(TUBB3):c.1228G>A (p.Glu410Lys)]

NM_006086.4(TUBB3):c.1228G>A (p.Glu410Lys)

Gene:
TUBB3:tubulin beta 3 class III [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
16q24.3
Genomic location:
Preferred name:
NM_006086.4(TUBB3):c.1228G>A (p.Glu410Lys)
HGVS:
  • NC_000016.10:g.89935679G>A
  • NG_027810.1:g.18671G>A
  • NM_001197181.2:c.1012G>A
  • NM_006086.4:c.1228G>AMANE SELECT
  • NP_001184110.1:p.Glu338Lys
  • NP_006077.2:p.Glu410Lys
  • NP_006077.2:p.Glu410Lys
  • NC_000016.9:g.90002087G>A
  • NM_006086.3:c.1228G>A
  • Q13509:p.Glu410Lys
Protein change:
E338K; GLU410LYS
Links:
UniProtKB: Q13509#VAR_062763; OMIM: 602661.0005; dbSNP: rs267607165
NCBI 1000 Genomes Browser:
rs267607165
Molecular consequence:
  • NM_001197181.2:c.1012G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_006086.4:c.1228G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
TUBB3-related disorder
Synonyms:
TUBB3-related condition; TUBB3-related disorders
Identifiers:

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004104041PreventionGenetics, part of Exact Sciences
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(May 10, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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 PreventionGenetics, part of Exact Sciences, SCV004104041.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

The TUBB3 c.1228G>A variant is predicted to result in the amino acid substitution p.Glu410Lys. This variant has been reported to occur de novo in multiple individuals affected by what is known as 'TUBB3 E410K syndrome' (Chew et al. 2013. PubMed ID: 23378218; Romaniello et al. 2017. PubMed ID: 28677066; Tischfield et al. 2010. PubMed ID: 20074521; Grant et al. 2018. PubMed ID: 30272120). Patients were reported to have congenital fibrosis of the extraocular muscles, facial weakness, developmental delay, and possible peripheral neuropathy; however, early signs of this disorder may include fetal distress, stridor, and/or tracheomalacia (Chew et al. 2013. PubMed ID: 23378218). In vitro functional studies indicate that the p.Glu410Lys change significantly inhibits axonal transport of vesicles and mitochondria (Niwa et al. 2013. PubMed ID: 23503589). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Given the evidence, we interpret c.1228G>A (p.Glu410Lys) as pathogenic.

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

Last Updated: Oct 26, 2024