Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001860408 | SCV000739743 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2016-05-06 | criteria provided, single submitter | clinical testing | The p.N270S variant (also known as c.809A>G), located in coding exon 5 of the TGFBR1 gene, results from an A to G substitution at nucleotide position 809. The asparagine at codon 270 is replaced by serine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. |
| Invitae | RCV001860408 | SCV002165912 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2024-01-05 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 270 of the TGFBR1 protein (p.Asn270Ser). This variant is present in population databases (rs201475375, gnomAD 0.004%). This missense change has been observed in individual(s) with clinical features of TGFBR1-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 520220). 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 not expected to disrupt TGFBR1 protein function with a negative predictive value of 80%. 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. |
| Gene |
RCV003231541 | SCV003930254 | uncertain significance | not provided | 2023-05-31 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |