Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000803964 | SCV000943852 | uncertain significance | Juvenile polyposis syndrome | 2023-10-24 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 153 of the SMAD4 protein (p.Pro153Ser). This variant is present in population databases (rs751763157, gnomAD 0.007%). This missense change has been observed in individual(s) with colorectal cancer (PMID: 28944238). ClinVar contains an entry for this variant (Variation ID: 649107). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. |
| Ambry Genetics | RCV002319109 | SCV001184501 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection; Hereditary cancer-predisposing syndrome | 2022-08-09 | criteria provided, single submitter | clinical testing | The p.P153S variant (also known as c.457C>T), located in coding exon 4 of the SMAD4 gene, results from a C to T substitution at nucleotide position 457. The proline at codon 153 is replaced by serine, an amino acid with similar properties. This variant was reported in a study of 1231 colorectal cancer cases and 93 unaffected controls who underwent multigene panel testing; it was seen in 1/548 colorectal cancer cases unselected by tumor immunohistochemistry or microsatellite stability testing (DeRycke MS et al. Mol Genet Genomic Med. 2017 Sep;5:553-569). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003323726 | SCV004028921 | uncertain significance | not specified | 2023-07-21 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV003472376 | SCV004202596 | uncertain significance | Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome | 2023-06-14 | criteria provided, single submitter | clinical testing |