Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000195779 | SCV000250927 | uncertain significance | not provided | 2014-01-11 | criteria provided, single submitter | clinical testing | p.Asn234Ile (AAC>ATC): c.701 A>T in exon 4 of the TGFBR2 gene (NM_003242.5)The N234I variant in the TGFBR2 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. The N234I variant is a non-conservative amino acid substitution as these residues differ in polarity, charge, size and/or other properties and is more likely to impact secondary structure. Although the N234 residue is conserved across species, in silico analysis was inconsistent with regard to the effect this variant may have on the protein structure/function. Nevertheless, the N234I variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.With the clinical and molecular information available at this time, we cannot definitively determine if N234I is a disease-causing mutation or a rare benign variant. This variant was found in TAAD |
| Invitae | RCV003765255 | SCV004696892 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2023-12-15 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 234 of the TGFBR2 protein (p.Asn234Ile). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of TGFBR2-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 213917). 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. 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. |