Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000426608 | SCV000536524 | uncertain significance | not provided | 2021-03-24 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); 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: 33195419, 31769227) |
Invitae | RCV001368997 | SCV001565423 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2024-01-23 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 355 of the TGFBR2 protein (p.Ala355Thr). This variant is present in population databases (no rsID available, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with TGFBR2-related conditions. ClinVar contains an entry for this variant (Variation ID: 393155). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on TGFBR2 protein function. This variant disrupts the p.Ala355 amino acid residue in TGFBR2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15731757). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |
Ai |
RCV000426608 | SCV002502121 | uncertain significance | not provided | 2022-02-25 | criteria provided, single submitter | clinical testing | |
MGZ Medical Genetics Center | RCV002289581 | SCV002581802 | uncertain significance | Loeys-Dietz syndrome 2 | 2022-08-22 | criteria provided, single submitter | clinical testing |