Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000540821 | SCV000658861 | pathogenic | Familial thoracic aortic aneurysm and aortic dissection | 2023-07-10 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with TGFBR1-related conditions and thoracic aortic aneurysm and dissection (PMID: 25326635, 27879313; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 477563). 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. This variant disrupts the p.His283 amino acid residue in TGFBR1. Other variant(s) that disrupt this residue have been observed in individuals with TGFBR1-related conditions (PMID: 27125181), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 283 of the TGFBR1 protein (p.His283Arg). |
| Baylor Genetics | RCV000680124 | SCV000807567 | uncertain significance | Loeys-Dietz syndrome 1 | 2017-09-01 | criteria provided, single submitter | clinical testing | Likely pathogenicity based on finding it once in our laboratory in a 1-year-old female (deceased) with Loeys-Dietz syndrome/acute hepatic encephalopathy; father (deceased, not tested) and fraternal twin sister (has the variant) also had Loeys-Dietz syndrome. |