ClinVar Miner

Submissions for variant NM_001379200.1(TBX1):c.1374C>G (p.His458Gln)

gnomAD frequency: 0.00005  dbSNP: rs747623105
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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 RCV001315139 SCV001505696 uncertain significance DiGeorge syndrome 2024-12-14 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 449 of the TBX1 protein (p.His449Gln). This variant is present in population databases (rs747623105, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with TBX1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1016174). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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 RCV002384396 SCV002690271 uncertain significance Cardiovascular phenotype 2018-12-07 criteria provided, single submitter clinical testing The p.H449Q variant (also known as c.1347C>G), located in coding exon 8 of the TBX1 gene, results from a C to G substitution at nucleotide position 1347. The histidine at codon 449 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is highly 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.
GeneDx RCV004779059 SCV005390630 uncertain significance not provided 2024-03-15 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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