Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000167191 | SCV000218028 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-03 | criteria provided, single submitter | clinical testing | The p.N1829Y variant (also known as c.5485A>T), located in coding exon 15 of the APC gene, results from an A to T substitution at nucleotide position 5485. The asparagine at codon 1829 is replaced by tyrosine, an amino acid with dissimilar 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. |
| Gene |
RCV000481452 | SCV000567371 | uncertain significance | not provided | 2015-07-17 | criteria provided, single submitter | clinical testing | This variant is denoted APC c.5485A>T at the cDNA level, p.Asn1829Tyr (N1829Y) at the protein level, and results in the change of an Asparagine to a Tyrosine (AAT>TAT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC Asn1829Tyr was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Asparagine and Tyrosine differ in some properties, this is considered a semi-conservative amino acid substitution. APC Asn1829Tyr occurs at a position where amino acids with properties similar to Asparagine are tolerated across species and is located in the 20-aa repeat B-catenin down-regulating domain as well as the SAMP repeat/axin binding domain (Azzopardi 2008). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether APC Asn1829Tyr is pathogenic or benign. We consider it to be a variant of uncertain significance. |
| Invitae | RCV002515174 | SCV003312403 | uncertain significance | Familial adenomatous polyposis 1 | 2022-02-07 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 1829 of the APC protein (p.Asn1829Tyr). 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: 187460). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. |