ClinVar Miner

Submissions for variant NM_181486.4(TBX5):c.1151C>T (p.Ala384Val)

gnomAD frequency: 0.00011  dbSNP: rs530882236
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000317914 SCV000339364 uncertain significance not provided 2016-02-24 criteria provided, single submitter clinical testing
Ambry Genetics RCV002348004 SCV002620497 uncertain significance Cardiovascular phenotype 2021-05-06 criteria provided, single submitter clinical testing The p.A384V variant (also known as c.1151C>T), located in coding exon 8 of the TBX5 gene, results from a C to T substitution at nucleotide position 1151. The alanine at codon 384 is replaced by valine, an amino acid with similar properties. This alteration is noted in a dilated cardiomyopathy (DCM) cohort (Mazzarotto F et al. Circulation, 2020 02;141:387-398). This amino acid position is well conserved in available vertebrate species; however, valine is the reference amino acid in other 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 RCV003765637 SCV004687044 uncertain significance Aortic valve disease 2 2023-05-24 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 384 of the TBX5 protein (p.Ala384Val). This variant is present in population databases (rs530882236, gnomAD 0.02%). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 31983221). ClinVar contains an entry for this variant (Variation ID: 286081). 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. 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.

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