Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003742751 | SCV000647620 | uncertain significance | Familial adenomatous polyposis 1 | 2021-06-26 | criteria provided, single submitter | clinical testing | 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. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. This variant is present in population databases (rs587782271, ExAC 0.002%) but has not been reported in the literature in individuals with an APC-related disease. This sequence change replaces serine with arginine at codon 2000 of the APC protein (p.Ser2000Arg). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and arginine. |
| Ambry Genetics | RCV002358547 | SCV002655737 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-10-10 | criteria provided, single submitter | clinical testing | The p.S2000R variant (also known as c.5998A>C), located in coding exon 15 of the APC gene, results from an A to C substitution at nucleotide position 5998. The serine at codon 2000 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is not well 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. |