NM_030773.4(TUBB1):c.952C>T (p.Arg318Trp) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 7, 2022
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:: RCV002512603.3

Allele description [Variation Report for NM_030773.4(TUBB1):c.952C>T (p.Arg318Trp)]

NM_030773.4(TUBB1):c.952C>T (p.Arg318Trp)

Gene:

TUBB1:tubulin beta 1 class VI [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

20q13.32

Genomic location:

Preferred name:

NM_030773.4(TUBB1):c.952C>T (p.Arg318Trp)

HGVS:

NC_000020.11:g.59024379C>T
NG_023424.2:g.10126C>T
NM_030773.4:c.952C>TMANE SELECT
NP_110400.1:p.Arg318Trp
NP_110400.1:p.Arg318Trp
LRG_581t1:c.952C>T
LRG_581:g.10126C>T
LRG_581p1:p.Arg318Trp
NC_000020.10:g.57599434C>T
NM_030773.3:c.952C>T
Q9H4B7:p.Arg318Trp

Protein change:

R318W; ARG318TRP

Links:

UniProtKB: Q9H4B7#VAR_063411; OMIM: 612901.0001; dbSNP: rs121918555

NCBI 1000 Genomes Browser:

rs121918555

Molecular consequence:

NM_030773.4:c.952C>T - 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
SCV003443381	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 7, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 31064749, 33400601, 18849486, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003443381

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 7, 2022)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

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

Diagnostic high-throughput sequencing of 2396 patients with bleeding, thrombotic, and platelet disorders.

Downes K, Megy K, Duarte D, Vries M, Gebhart J, Hofer S, Shamardina O, Deevi SVV, Stephens J, Mapeta R, Tuna S, Al Hasso N, Besser MW, Cooper N, Daugherty L, Gleadall N, Greene D, Haimel M, Martin H, Papadia S, Revel-Vilk S, Sivapalaratnam S, et al.

Blood. 2019 Dec 5;134(23):2082-2091. doi: 10.1182/blood.2018891192.

PubMed [citation]

PMID:: 31064749
PMCID:: PMC6993014

Identification of a pathogenic TUBB1 variant in a Chinese family with congenital macrothrombocytopenia through whole genome sequencing.

Hou Y, Shao L, Zhou H, Liu Y, Fisk DG, Spiteri E, Zehnder JL, Peng J, Zhang BM, Hou M.

Platelets. 2021 Nov 17;32(8):1108-1112. doi: 10.1080/09537104.2020.1869714. Epub 2021 Jan 5.

PubMed [citation]

PMID:: 33400601

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003443381.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 318 of the TUBB1 protein (p.Arg318Trp). This variant is present in population databases (rs121918555, gnomAD 0.06%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with clinical features of TUBB1-related macrothrombocytopenia (PMID: 18849486, 31064749, 33400601). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 425). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). Experimental studies have shown that this missense change affects TUBB1 function (PMID: 18849486). For these reasons, this variant has been 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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