Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001223075 | SCV001395208 | uncertain significance | DiGeorge syndrome | 2024-08-13 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 494 of the TBX1 protein (p.Pro494Arg). This variant is present in population databases (rs756769832, gnomAD 0.01%). 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: 951216). 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 | RCV003163735 | SCV003882794 | uncertain significance | Cardiovascular phenotype | 2022-11-04 | criteria provided, single submitter | clinical testing | The p.P494R variant (also known as c.1481C>G), located in coding exon 8 of the TBX1 gene, results from a C to G substitution at nucleotide position 1481. The proline at codon 494 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is conserved. 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. |
Prevention |
RCV003393895 | SCV004120362 | uncertain significance | TBX1-related disorder | 2023-03-29 | criteria provided, single submitter | clinical testing | The TBX1 c.1481C>G variant is predicted to result in the amino acid substitution p.Pro494Arg. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.012% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/22-19754383-C-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |