ClinVar Miner

Submissions for variant NM_181486.4(TBX5):c.1064G>A (p.Arg355His)

gnomAD frequency: 0.00004  dbSNP: rs145784562
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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 RCV000554045 SCV000659011 uncertain significance Aortic valve disease 2 2024-10-03 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 355 of the TBX5 protein (p.Arg355His). This variant is present in population databases (rs145784562, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with TBX5-related conditions. ClinVar contains an entry for this variant (Variation ID: 477654). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt TBX5 protein function with a negative predictive value of 80%. 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.
Ambry Genetics RCV002413650 SCV002712091 uncertain significance Cardiovascular phenotype 2024-10-08 criteria provided, single submitter clinical testing The p.R355H variant (also known as c.1064G>A), located in coding exon 8 of the TBX5 gene, results from a G to A substitution at nucleotide position 1064. The arginine at codon 355 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002491110 SCV002776874 uncertain significance Holt-Oram syndrome 2021-10-10 criteria provided, single submitter clinical testing

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