NM_178012.5(TUBB2B):c.703G>A (p.Gly235Arg) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Apr 20, 2023
Review status:: criteria provided, conflicting classifications

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:: RCV000993525.8

Allele description [Variation Report for NM_178012.5(TUBB2B):c.703G>A (p.Gly235Arg)]

NM_178012.5(TUBB2B):c.703G>A (p.Gly235Arg)

Gene:

TUBB2B:tubulin beta 2B class IIb [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p25.2

Genomic location:

Preferred name:

NM_178012.5(TUBB2B):c.703G>A (p.Gly235Arg)

HGVS:

NC_000006.12:g.3225386C>T
NG_016715.1:g.7349G>A
NM_178012.5:c.703G>AMANE SELECT
NP_821080.1:p.Gly235Arg
NC_000006.11:g.3225620C>T
NM_178012.4:c.703G>A

Protein change:

G235R

Links:

dbSNP: rs587784500

NCBI 1000 Genomes Browser:

rs587784500

Molecular consequence:

NM_178012.5:c.703G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001146568	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Benign (Mar 5, 2019)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 22333901, 26467025
SCV001831757	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Benign (Sep 2, 2019)	germline	clinical testing	Citation Link,
SCV003246775	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 20, 2023)	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

SCV001146568

Athena Diagnostics

criteria provided, single submitter

(Athena Diagnostics Criteria)

Benign
(Mar 5, 2019)

germline

clinical testing

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

SCV001831757

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Benign
(Sep 2, 2019)

germline

clinical testing

Citation Link,

SCV003246775

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 20, 2023)

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Symmetric polymicrogyria and pachygyria associated with TUBB2B gene mutations.

Guerrini R, Mei D, Cordelli DM, Pucatti D, Franzoni E, Parrini E.

Eur J Hum Genet. 2012 Sep;20(9):995-8. doi: 10.1038/ejhg.2012.21. Epub 2012 Feb 15.

PubMed [citation]

PMID:: 22333901
PMCID:: PMC3421113

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

See all PubMed Citations (3)

Details of each submission

From Athena Diagnostics, SCV001146568.1

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

#	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

From GeneDx, SCV001831757.1

#	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	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003246775.2

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

Description

Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TUBB2B protein function. ClinVar contains an entry for this variant (Variation ID: 160184). This variant has not been reported in the literature in individuals affected with TUBB2B-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 235 of the TUBB2B protein (p.Gly235Arg). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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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