Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001039839 | SCV000319470 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2015-03-04 | criteria provided, single submitter | clinical testing | The p.R11P variant (also known as c.32G>C), located in coding exon 1 of the TGFBR1 gene, results from a G to C substitution at nucleotide position 32. The arginine at codon 11 is replaced by proline, an amino acid with dissimilar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 779 samples (1558 alleles) with coverage at this position. This amino acid position is poorly conserved in available vertebrate species on limited alignment. 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 | RCV001039839 | SCV001203388 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2023-08-17 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 11 of the TGFBR1 protein (p.Arg11Pro). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with TGFBR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 263928). 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. 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. |