Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001026192 | SCV001188526 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-03-05 | criteria provided, single submitter | clinical testing | The p.L2416F variant (also known as c.7246C>T), located in coding exon 15 of the APC gene, results from a C to T substitution at nucleotide position 7246. The leucine at codon 2416 is replaced by phenylalanine, 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. |
| Invitae | RCV002236290 | SCV001559943 | uncertain significance | Familial adenomatous polyposis 1 | 2020-01-29 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with phenylalanine at codon 2416 of the APC protein (p.Leu2416Phe). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and phenylalanine. 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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). |