ClinVar Miner

Submissions for variant NM_181486.4(TBX5):c.1396G>A (p.Val466Met)

gnomAD frequency: 0.00006  dbSNP: rs765443283
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001901701 SCV002172097 uncertain significance Aortic valve disease 2 2021-03-04 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 466 of the TBX5 protein (p.Val466Met). The valine residue is moderately conserved and there is a small physicochemical difference between valine and methionine. 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. This variant has not been reported in the literature in individuals with TBX5-related conditions. This variant is present in population databases (rs765443283, ExAC 0.002%).
Ambry Genetics RCV002388807 SCV002701693 uncertain significance Cardiovascular phenotype 2017-12-20 criteria provided, single submitter clinical testing The p.V466M variant (also known as c.1396G>A), located in coding exon 8 of the TBX5 gene, results from a G to A substitution at nucleotide position 1396. The valine at codon 466 is replaced by methionine, an amino acid with highly similar properties. 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.
Fulgent Genetics, Fulgent Genetics RCV002507009 SCV002815204 uncertain significance Holt-Oram syndrome 2021-10-28 criteria provided, single submitter clinical testing

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