Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV000583866 | SCV000686931 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-05 | criteria provided, single submitter | clinical testing | This missense variant replaces asparagine with serine at codon 1122 of the APC protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with APC-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Laboratory for Molecular Medicine, |
RCV000611424 | SCV000731319 | uncertain significance | not specified | 2016-12-21 | criteria provided, single submitter | clinical testing | The p.Asn1122Ser variant in APC has not been previously reported in individuals with APC-associated polyposis, but has been identified in 1/8600 European chromo somes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs372855304). Computational prediction tools and conservation analysis sug gest that the p.Asn1122Ser variant may not impact the protein, though this infor mation is not predictive enough to rule out pathogenicity. In summary, the clini cal significance of the p.Asn1122Ser variant is uncertain. |
Invitae | RCV002529141 | SCV000768035 | uncertain significance | Familial adenomatous polyposis 1 | 2023-12-25 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 1122 of the APC protein (p.Asn1122Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 490261). 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) performed at Invitae indicates that this missense variant is not expected to disrupt APC protein function with a negative predictive value of 95%. 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 | RCV000583866 | SCV002612941 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-17 | criteria provided, single submitter | clinical testing | The p.N1122S variant (also known as c.3365A>G), located in coding exon 15 of the APC gene, results from an A to G substitution at nucleotide position 3365. The asparagine at codon 1122 is replaced by serine, an amino acid with highly similar properties. In one study, this alteration was identified in 1/1162 sarcoma patients; however, no features of familial adenomatous polyposis were mentioned by the study authors (Ballinger ML et al. Lancet Oncol, 2016 Sep;17:1261-71). In another study, this variant was detected in 0/165 colorectal cancer and/or polyposis patients and was identified in 1/2512 control individuals from a healthy population database (Rosenthal EA et al. Hum Genet, 2018 Oct;137:795-806). Additionally, this alteration was detected in a study of 1,165 individuals with a history of colorectal cancer or colon polyps as well as 590 controls (Gordon AS et al. Am J Hum Genet, 2019 09;105:526-533). 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. |
Fulgent Genetics, |
RCV002491154 | SCV002779301 | uncertain significance | Desmoid disease, hereditary; Familial adenomatous polyposis 1; Hepatocellular carcinoma; Gastric cancer; Colorectal cancer; Gastric adenocarcinoma and proximal polyposis of the stomach | 2022-04-07 | criteria provided, single submitter | clinical testing |