Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001224907 | SCV001397134 | uncertain significance | Juvenile polyposis syndrome | 2019-04-06 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine with glutamic acid at codon 180 of the SMAD4 protein (p.Gln180Glu). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and glutamic 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 tolerated, 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 SMAD4-related conditions. This variant is not present in population databases (ExAC no frequency). |
| Ambry Genetics | RCV002348755 | SCV002642811 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection; Hereditary cancer-predisposing syndrome | 2020-07-22 | criteria provided, single submitter | clinical testing | The p.Q180E variant (also known as c.538C>G), located in coding exon 4 of the SMAD4 gene, results from a C to G substitution at nucleotide position 538. The glutamine at codon 180 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. 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. |