ClinVar Miner

Submissions for variant NM_001379200.1(TBX1):c.617C>T (p.Pro206Leu)

gnomAD frequency: 0.00003  dbSNP: rs766608075
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000483932 SCV000565998 uncertain significance not provided 2024-11-15 criteria provided, single submitter clinical testing Reported de novo in at least one individual from large cohort studies with autism spectrum disorder, but detailed clinical information was not provided (PMID: 33057194, 35982160, 35982159); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 33057194, 35982160, 35982159)
Athena Diagnostics RCV000483932 SCV001146091 uncertain significance not provided 2019-08-05 criteria provided, single submitter clinical testing
Ambry Genetics RCV002356767 SCV002652592 uncertain significance Cardiovascular phenotype 2022-04-09 criteria provided, single submitter clinical testing The p.P197L variant (also known as c.590C>T), located in coding exon 4 of the TBX1 gene, results from a C to T substitution at nucleotide position 590. The proline at codon 197 is replaced by leucine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious 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 RCV005090928 SCV005775891 uncertain significance DiGeorge syndrome 2024-11-19 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 197 of the TBX1 protein (p.Pro197Leu). This variant is present in population databases (rs766608075, gnomAD 0.009%). This missense change has been observed in individual(s) with clinical features of TBX1-related conditions (PMID: 33057194). ClinVar contains an entry for this variant (Variation ID: 418725). 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 expected to disrupt TBX1 protein function with a positive 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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