ClinVar Miner

Submissions for variant NM_181486.4(TBX5):c.1348C>G (p.Leu450Val)

gnomAD frequency: 0.00001  dbSNP: rs1243477560
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002010047 SCV002281802 uncertain significance Aortic valve disease 2 2021-06-02 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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. This variant has not been reported in the literature in individuals with TBX5-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with valine at codon 450 of the TBX5 protein (p.Leu450Val). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and valine.
Ambry Genetics RCV003170441 SCV003911894 uncertain significance Cardiovascular phenotype 2023-02-16 criteria provided, single submitter clinical testing The p.L450V variant (also known as c.1348C>G), located in coding exon 8 of the TBX5 gene, results from a C to G substitution at nucleotide position 1348. The leucine at codon 450 is replaced by valine, an amino acid with highly similar properties. This amino acid position is conserved. 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.

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.