NM_001321120.2(TBX4):c.748del (p.Arg250fs) AND TBX4-related disorder

Germline classification:: Likely pathogenic (1 submission)
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:: RCV003335974.1

Allele description [Variation Report for NM_001321120.2(TBX4):c.748del (p.Arg250fs)]

NM_001321120.2(TBX4):c.748del (p.Arg250fs)

Gene:

TBX4:T-box transcription factor 4 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

17q23.2

Genomic location:

Preferred name:

NM_001321120.2(TBX4):c.748del (p.Arg250fs)

HGVS:

NC_000017.11:g.61479926del
NG_008080.1:g.28481del
NM_001321120.2:c.748delMANE SELECT
NM_018488.3:c.748del
NP_001308049.1:p.Arg250fs
NP_060958.2:p.Arg250fs
LRG_1206t1:c.748del
LRG_1206:g.28481del
LRG_1206p1:p.Arg250fs
NC_000017.10:g.59557287del

Protein change:

R250fs

Molecular consequence:

NM_001321120.2:c.748del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_018488.3:c.748del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: TBX4-related disorder
Synonyms:: TBX4-Related Disorders; TBX4-related condition
Identifiers:

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004046418	Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic	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

SCV004046418

Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic

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

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 Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego, SCV004046418.1

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

Description

This frameshifting variant in exon 6 of 8 introduces a premature stop codon and is therefore predicted to result in loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay (NMD). This variant has not been previously reported or functionally characterized in the literature to our knowledge. Loss-of-function variation in TBX4 is an established mechanism of disease (PMID: 31151956). The c.748del (p.Arg250GlyfsTer20) variant is absent from the gnomAD population database and thus is presumed to be rare. Based on the available evidence, the c.748del (p.Arg250GlyfsTer20) variant is classified as Likely Pathogenic.

#	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

Last Updated: May 19, 2024

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