ClinVar Miner

Submissions for variant NM_181486.4(TBX5):c.848C>A (p.Thr283Asn)

gnomAD frequency: 0.00005  dbSNP: rs147077037
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000595942 SCV000704955 uncertain significance not provided 2017-01-19 criteria provided, single submitter clinical testing
Ambry Genetics RCV000619481 SCV000738014 uncertain significance Cardiovascular phenotype 2022-08-09 criteria provided, single submitter clinical testing The p.T283N variant (also known as c.848C>A), located in coding exon 7 of the TBX5 gene, results from a C to A substitution at nucleotide position 848. The threonine at codon 283 is replaced by asparagine, an amino acid with similar properties. This alteration was reported in both affected and unaffected individuals from a family with limb abnormalities (Alves LU et al. J Hum Genet, 2017 Dec;62:1073-1078). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001226522 SCV001398838 uncertain significance Aortic valve disease 2 2022-12-09 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TBX5 protein function. ClinVar contains an entry for this variant (Variation ID: 499465). This variant has not been reported in the literature in individuals affected with TBX5-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces threonine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 283 of the TBX5 protein (p.Thr283Asn).
Fulgent Genetics, Fulgent Genetics RCV002483606 SCV002794071 uncertain significance Holt-Oram syndrome 2021-10-02 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.