Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002231710 | SCV000632746 | uncertain significance | Juvenile polyposis syndrome | 2017-01-26 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with arginine at codon 359 of the SMAD4 protein (p.Gly359Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a SMAD4-related disease. In summary, this variant is a novel missense change with uncertain impact on protein function. 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). |
Ambry Genetics | RCV002420398 | SCV002720209 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection; Hereditary cancer-predisposing syndrome | 2022-03-12 | criteria provided, single submitter | clinical testing | The p.G359R variant (also known as c.1075G>C), located in coding exon 8 of the SMAD4 gene, results from a G to C substitution at nucleotide position 1075. The glycine at codon 359 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |