Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000196433 | SCV000250893 | uncertain significance | not provided | 2020-10-15 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect |
Invitae | RCV001857726 | SCV002259325 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2021-06-18 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with TGFBR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 213889). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with lysine at codon 382 of the TGFBR1 protein (p.Glu382Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. 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. 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. |