Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000561789 | SCV000667748 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-05-22 | criteria provided, single submitter | clinical testing | The p.L841F variant (also known as c.2523A>C), located in coding exon 15 of the APC gene, results from an A to C substitution at nucleotide position 2523. The leucine at codon 841 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 | RCV003744557 | SCV003278954 | uncertain significance | Familial adenomatous polyposis 1 | 2021-12-30 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 841 of the APC protein (p.Leu841Phe). ClinVar contains an entry for this variant (Variation ID: 482479). 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. |