Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001071283 | SCV001236578 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2019-10-18 | 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 been observed in individuals with TGFBR2-related conditions (PMID: 27879313, Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with arginine at codon 381 of the TGFBR2 protein (p.Lys381Arg). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and arginine. |