Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001347685 | SCV001541958 | uncertain significance | DiGeorge syndrome | 2020-10-27 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with TBX1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces tyrosine with cysteine at codon 426 of the TBX1 protein (p.Tyr426Cys). The tyrosine residue is moderately conserved and there is a large physicochemical difference between tyrosine and cysteine. |
Prevention |
RCV003399134 | SCV004103505 | uncertain significance | TBX1-related condition | 2023-03-10 | criteria provided, single submitter | clinical testing | The TBX1 c.1277A>G variant is predicted to result in the amino acid substitution p.Tyr426Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0012% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/22-19754179-A-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |