Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000492978 | SCV000581913 | likely pathogenic | not provided | 2019-09-19 | 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 | RCV001061635 | SCV001226384 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2019-11-18 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with TGFBR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 429361). This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with leucine at codon 436 of the TGFBR1 protein (p.Pro436Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. |