NM_181486.4(TBX5):c.709C>T (p.Arg237Trp) AND Holt-Oram syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jun 14, 2018
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000008459.5

Allele description [Variation Report for NM_181486.4(TBX5):c.709C>T (p.Arg237Trp)]

NM_181486.4(TBX5):c.709C>T (p.Arg237Trp)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

12q24.21

Genomic location:

Preferred name:

NM_181486.4(TBX5):c.709C>T (p.Arg237Trp)

HGVS:

NC_000012.12:g.114385522G>A
NG_007373.1:g.27921C>T
NM_000192.3:c.709C>T
NM_080717.4:c.559C>T
NM_181486.4:c.709C>TMANE SELECT
NP_000183.2:p.Arg237Trp
NP_542448.1:p.Arg187Trp
NP_852259.1:p.Arg237Trp
LRG_670t1:c.709C>T
LRG_670:g.27921C>T
LRG_670p1:p.Arg237Trp
NC_000012.11:g.114823327G>A
Q99593:p.Arg237Trp

Protein change:

R187W; ARG237TRP

Links:

UniProtKB: Q99593#VAR_009702; OMIM: 601620.0005; dbSNP: rs104894382

NCBI 1000 Genomes Browser:

rs104894382

Molecular consequence:

NM_000192.3:c.709C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_080717.4:c.559C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_181486.4:c.709C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Holt-Oram syndrome (HOS)
Synonyms:: Ventriculo-radial syndrome; Atrio digital syndrome; Cardiac-limb syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007732; MedGen: C0265264; Orphanet: 392; OMIM: 142900

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zinc finger matrin-type protein 2 [Homo sapiens]
zinc finger matrin-type protein 2 [Homo sapiens]
gi|21389511|ref|NP_653324.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000028667	OMIM	no assertion criteria provided	Pathogenic (Mar 16, 1999)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000920840	Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille	no assertion criteria provided	Pathogenic (Jun 14, 2018)	paternal, unknown	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000028667

OMIM

no assertion criteria provided

Pathogenic
(Mar 16, 1999)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

SCV000920840

Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille

no assertion criteria provided

Pathogenic
(Jun 14, 2018)

paternal, unknown

clinical testing

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	paternal	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Different TBX5 interactions in heart and limb defined by Holt-Oram syndrome mutations.

Basson CT, Huang T, Lin RC, Bachinsky DR, Weremowicz S, Vaglio A, Bruzzone R, Quadrelli R, Lerone M, Romeo G, Silengo M, Pereira A, Krieger J, Mesquita SF, Kamisago M, Morton CC, Pierpont ME, Müller CW, Seidman JG, Seidman CE.

Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):2919-24.

PubMed [citation]

PMID:: 10077612
PMCID:: PMC15870

Details of each submission

From OMIM, SCV000028667.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In families with Holt-Oram syndrome (HOS; 142900), Basson et al. (1999) identified an arg237-to-trp substitution in the TBX5 gene. The mutation occurred in the same codon as the arg237-to-gln mutation (601620.0003), and the authors found that both mutations caused extensive upper limb malformations but less significant cardiac abnormalities. They found that residue 80 (601620.0004) is highly conserved within T-box sequences that interact with the major group of target DNA, whereas residue 237 is located in the T-box domain that selectively binds to the minor group DNA.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille, SCV000920840.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided
2	not provided	not provided	not provided	not provided	clinical testing	not provided
3	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	paternal	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided
2	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided
3	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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