Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001023403 | SCV001185272 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-11-09 | criteria provided, single submitter | clinical testing | The p.N1667S variant (also known as c.5000A>G), located in coding exon 15 of the APC gene, results from an A to G substitution at nucleotide position 5000. The asparagine at codon 1667 is replaced by serine, 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. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001800936 | SCV002047064 | uncertain significance | not provided | 2021-05-10 | criteria provided, single submitter | clinical testing | |
Invitae | RCV003649220 | SCV002292825 | uncertain significance | Familial adenomatous polyposis 1 | 2021-07-01 | 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. ClinVar contains an entry for this variant (Variation ID: 825363). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces asparagine with serine at codon 1667 of the APC protein (p.Asn1667Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. |