Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute of Human Genetics, |
RCV000578422 | SCV000680402 | likely pathogenic | Tetralogy of Fallot | 2017-12-13 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000702287 | SCV000831135 | uncertain significance | DiGeorge Syndrome | 2018-08-16 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid with lysine at codon 129 of the TBX1 protein (p.Glu129Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with a TBX1-related disease in one family (Invitae). ClinVar contains an entry for this variant (Variation ID: 488618). Experimental studies have shown that this missense change results in significantly reduced transcriptional activity compared to wild type TBX1 protein (PMID: 24998776, 28272434). 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. |