Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000635482 | SCV000756896 | uncertain significance | Juvenile polyposis syndrome | 2023-08-27 | criteria provided, single submitter | clinical testing | Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SMAD4 protein function. 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. ClinVar contains an entry for this variant (Variation ID: 529949). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 286 of the SMAD4 protein (p.Gly286Ser). This variant is present in population databases (rs750111831, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with SMAD4-related conditions. |
| Ambry Genetics | RCV002448964 | SCV002676324 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection; Hereditary cancer-predisposing syndrome | 2022-09-27 | criteria provided, single submitter | clinical testing | The p.G286S variant (also known as c.856G>A), located in coding exon 6 of the SMAD4 gene, results from a G to A substitution at nucleotide position 856. The glycine at codon 286 is replaced by serine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Baylor Genetics | RCV003471995 | SCV004202570 | uncertain significance | Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome | 2023-10-19 | criteria provided, single submitter | clinical testing |