Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000038241 | SCV000061909 | uncertain significance | not specified | 2012-02-21 | criteria provided, single submitter | clinical testing | The Leu260Gln variant (TGFBR1) has not been reported in the literature nor previ ously identified by our laboratory. Computational analyses (biochemical amino ac id properties, conservation, PolyPhen2, and SIFT) suggest that the Leu260Gln var iant may impact the protein, though this information is not predictive enough to determine pathogenicity. In the absence of additional information, the clinical significance of the this variant cannot be assessed at this time. |
| Invitae | RCV002514151 | SCV003257314 | pathogenic | Familial thoracic aortic aneurysm and aortic dissection | 2022-01-20 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 TGFBR1 protein function. ClinVar contains an entry for this variant (Variation ID: 45099). This missense change has been observed in individual(s) with clinical features of Loeys-Dietz syndrome (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 260 of the TGFBR1 protein (p.Leu260Gln). |