Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Centre for Mendelian Genomics, |
RCV001196257 | SCV001366814 | likely pathogenic | Malignant tumor of esophagus | 2016-01-01 | criteria provided, single submitter | clinical testing | This variant was classified as: Likely pathogenic. |
Invitae | RCV001863104 | SCV002176404 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2021-06-29 | criteria provided, single submitter | clinical testing | 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 expected to disrupt TGFBR2 protein function. ClinVar contains an entry for this variant (Variation ID: 930524). This variant has not been reported in the literature in individuals affected with TGFBR2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with proline at codon 452 of the TGFBR2 protein (p.Leu452Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. 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. |