Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000586639 | SCV000698191 | uncertain significance | not specified | 2022-12-20 | criteria provided, single submitter | clinical testing | Variant summary: TGFBR2 c.1163A>G (p.Lys388Arg) results in a conservative amino acid change located in the kinase domain (IPR000719) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 250540 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.1163A>G in individuals affected with Loeys-Dietz Syndrome 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 and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
Invitae | RCV000654810 | SCV000776710 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2021-05-10 | 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 do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). This variant has not been reported in the literature in individuals with TGFBR2-related disease. ClinVar contains an entry for this variant (Variation ID: 36863). This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with arginine at codon 388 of the TGFBR2 protein (p.Lys388Arg). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and arginine. |