Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003534694 | SCV000830310 | uncertain significance | Familial adenomatous polyposis 1 | 2018-02-28 | criteria provided, single submitter | clinical testing | This variant, c.4416_4427dupAAATGCTGCAGT, results in the insertion of 4 amino acids to the APC protein (p.Asn1473_Val1476dup), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with APC-related disease. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the duplicated  amino acids is currently unknown. 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 | RCV003165871 | SCV003866280 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-15 | criteria provided, single submitter | clinical testing | The c.4416_4427dup12 variant (also known as p.N1473_V1476dup), located in coding exon 15 of the APC gene, results from an in-frame duplication of 12 nucleotides at nucleotide positions 4416 to 4427. This results in the duplication of 4 extra residues (NAAV) between codons 1473 and 1476. These amino acid positions are well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |