NM_001379200.1(TBX1):c.199_224del (p.Pro67fs) AND DiGeorge syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 11, 2019
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:: RCV001220575.4

Allele description [Variation Report for NM_001379200.1(TBX1):c.199_224del (p.Pro67fs)]

NM_001379200.1(TBX1):c.199_224del (p.Pro67fs)

Gene:

TBX1:T-box transcription factor 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

22q11.21

Genomic location:

Preferred name:

NM_001379200.1(TBX1):c.199_224del (p.Pro67fs)

HGVS:

NC_000022.11:g.19761042_19761067del
NG_009229.1:g.9340_9365del
NM_001379200.1:c.199_224delMANE SELECT
NM_005992.1:c.172_197del
NM_080646.2:c.172_197del
NM_080647.1:c.172_197del
NP_001366129.1:p.Pro67fs
NP_005983.1:p.Pro58fs
NP_542377.1:p.Pro58fs
NP_542378.1:p.Pro58fs
LRG_226t1:c.172_197del
LRG_226:g.9340_9365del
LRG_226p1:p.Pro58fs
NC_000022.10:g.19748554_19748579del
NC_000022.10:g.19748565_19748590del

Protein change:

P58fs

Links:

dbSNP: rs1936640897

NCBI 1000 Genomes Browser:

rs1936640897

Molecular consequence:

NM_001379200.1:c.199_224del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_005992.1:c.172_197del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_080646.2:c.172_197del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_080647.1:c.172_197del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: DiGeorge syndrome
Synonyms:: THIRD AND FOURTH PHARYNGEAL POUCH SYNDROME; Catch22
Identifiers:: MONDO: MONDO:0008564; MedGen: C0012236; Orphanet: 567; OMIM: 188400

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001392573	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 11, 2019)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 11239417, 11242049, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001392573

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 11, 2019)

germline

clinical testing

PubMed (3)
[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

TBX1 is responsible for cardiovascular defects in velo-cardio-facial/DiGeorge syndrome.

Merscher S, Funke B, Epstein JA, Heyer J, Puech A, Lu MM, Xavier RJ, Demay MB, Russell RG, Factor S, Tokooya K, Jore BS, Lopez M, Pandita RK, Lia M, Carrion D, Xu H, Schorle H, Kobler JB, Scambler P, Wynshaw-Boris A, Skoultchi AI, et al.

Cell. 2001 Feb 23;104(4):619-29.

PubMed [citation]

PMID:: 11239417

Tbx1 haploinsufficieny in the DiGeorge syndrome region causes aortic arch defects in mice.

Lindsay EA, Vitelli F, Su H, Morishima M, Huynh T, Pramparo T, Jurecic V, Ogunrinu G, Sutherland HF, Scambler PJ, Bradley A, Baldini A.

Nature. 2001 Mar 1;410(6824):97-101.

PubMed [citation]

PMID:: 11242049

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001392573.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Pro58Alafs*102) in the TBX1 gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has not been reported in the literature in individuals with TBX1-related conditions. Loss-of-function variants in TBX1 are known to be pathogenic (PMID: 11239417, 11242049). 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: May 16, 2025

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