ClinVar Miner

Submissions for variant NM_001379200.1(TBX1):c.323C>A (p.Ala108Glu)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002442072 SCV002751577 uncertain significance Cardiovascular phenotype 2022-07-05 criteria provided, single submitter clinical testing The p.A99E variant (also known as c.296C>A), located in coding exon 2 of the TBX1 gene, results from a C to A substitution at nucleotide position 296. The alanine at codon 99 is replaced by glutamic acid, an amino acid with dissimilar 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV003775431 SCV004611563 uncertain significance DiGeorge syndrome 2024-01-02 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 99 of the TBX1 protein (p.Ala99Glu). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 1798258). 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 TBX1 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.

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