Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003650694 | SCV001382644 | uncertain significance | Familial adenomatous polyposis 1 | 2019-07-04 | criteria provided, single submitter | clinical testing | 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 APC-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with asparagine at codon 843 of the APC protein (p.Ser843Asn). The serine residue is moderately conserved and there is a small physicochemical difference between serine and asparagine. |
Ambry Genetics | RCV002429895 | SCV002742081 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-05-20 | criteria provided, single submitter | clinical testing | The p.S843N variant (also known as c.2528G>A), located in coding exon 15 of the APC gene, results from a G to A substitution at nucleotide position 2528. The serine at codon 843 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is 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. |