Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000429672 | SCV000536507 | likely pathogenic | not provided | 2020-11-10 | 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: 28729728, 29543232) |
Invitae | RCV003642890 | SCV004560217 | likely pathogenic | Familial thoracic aortic aneurysm and aortic dissection | 2023-08-02 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with TGFBR2-related conditions (PMID: 29543232). This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 537 of the TGFBR2 protein (p.Arg537His). ClinVar contains an entry for this variant (Variation ID: 393141). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Arg537 amino acid residue in TGFBR2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15235604, 18781618, 21098638, 21324918, 22734312). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |