Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000804717 | SCV000944639 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2018-07-26 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with aspartic acid at codon 447 of the TGFBR2 protein (p.Val447Asp). The valine residue is highly conserved and there is a large physicochemical difference between valine and aspartic acid. 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 TGFBR2-related disease. This variant is not present in population databases (ExAC no frequency). |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV002307620 | SCV002600604 | uncertain significance | not specified | 2022-10-20 | criteria provided, single submitter | clinical testing | Variant summary: TGFBR2 c.1340T>A (p.Val447Asp) results in a non-conservative amino acid change located in the Protein kinase domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251472 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1340T>A in individuals affected with Aortopathy and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |