NM_181486.4(TBX5):c.100dup (p.Ala34fs) AND Aortic valve disease 2

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 21, 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:: RCV003531564.2

Allele description [Variation Report for NM_181486.4(TBX5):c.100dup (p.Ala34fs)]

NM_181486.4(TBX5):c.100dup (p.Ala34fs)

Gene:

TBX5:T-box transcription factor 5 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

12q24.21

Genomic location:

Preferred name:

NM_181486.4(TBX5):c.100dup (p.Ala34fs)

HGVS:

NC_000012.12:g.114403802dup
NG_007373.1:g.9644dup
NM_000192.3:c.100dup
NM_080717.4:c.-3-1879dup
NM_181486.4:c.100dupMANE SELECT
NP_000183.2:p.Ala34fs
NP_852259.1:p.Ala34fs
LRG_670t1:c.100dup
LRG_670:g.9644dup
LRG_670p1:p.Ala34fs
NC_000012.11:g.114841603_114841604insC
NC_000012.11:g.114841607dup

Protein change:

A34fs

Molecular consequence:

NM_000192.3:c.100dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_181486.4:c.100dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_080717.4:c.-3-1879dup - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Aortic valve disease 2 (AOVD2)
Identifiers:: MONDO: MONDO:0013902; MedGen: C3542024; OMIM: 614823

Recent activity

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Ribosomal protein S3Ae [Arabidopsis thaliana]
Ribosomal protein S3Ae [Arabidopsis thaliana]
gi|15236171|ref|NP_195193.1|

Protein
Yucca gloriosa cultivar:6.0.2.2015
Yucca gloriosa cultivar:6.0.2.2015
Yucca gloriosa 6.0.2.2015 gene expression profiling

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004296236	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 21, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 12789647, 16183809, 16917909, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004296236

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 21, 2023)

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

Expressivity of Holt-Oram syndrome is not predicted by TBX5 genotype.

Brassington AM, Sung SS, Toydemir RM, Le T, Roeder AD, Rutherford AE, Whitby FG, Jorde LB, Bamshad MJ.

Am J Hum Genet. 2003 Jul;73(1):74-85. Epub 2003 Jun 3.

PubMed [citation]

PMID:: 12789647
PMCID:: PMC1180592

TBX5 genetic testing validates strict clinical criteria for Holt-Oram syndrome.

McDermott DA, Bressan MC, He J, Lee JS, Aftimos S, Brueckner M, Gilbert F, Graham GE, Hannibal MC, Innis JW, Pierpont ME, Raas-Rothschild A, Shanske AL, Smith WE, Spencer RH, St John-Sutton MG, van Maldergem L, Waggoner DJ, Weber M, Basson CT.

Pediatr Res. 2005 Nov;58(5):981-6. Epub 2005 Sep 23.

PubMed [citation]

PMID:: 16183809

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004296236.1

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant is also known as 100-101insG, p.G33fs. This premature translational stop signal has been observed in individuals with Holt-Oram syndrome (PMID: 12789647, 16917909). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ala34Glyfs*27) in the TBX5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TBX5 are known to be pathogenic (PMID: 16183809, 16917909).

#	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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