Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001023577 | SCV001185477 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-09-30 | criteria provided, single submitter | clinical testing | The p.S1707F variant (also known as c.5120C>T), located in coding exon 15 of the APC gene, results from a C to T substitution at nucleotide position 5120. The serine at codon 1707 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This amino acid position is not well conserved in available vertebrate species. Missense alterations in APC are not a common cause of disease (Spier I et al. Genet Med. 2024 Feb;26(2):100992). In addition, in silico predictors for this gene do not accurately predict pathogenicity. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV004563700 | SCV002235404 | uncertain significance | Familial adenomatous polyposis 1 | 2021-08-31 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with phenylalanine at codon 1707 of the APC protein (p.Ser1707Phe). The serine residue is moderately conserved and there is a large physicochemical difference between serine and phenylalanine. This variant is not present in population databases (ExAC 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: 825464). 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: "Benign"; 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. |
| All of Us Research Program, |
RCV004004637 | SCV004821568 | uncertain significance | Classic or attenuated familial adenomatous polyposis | 2023-02-15 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with phenylalanine at codon 1707 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 hereditary cancer 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. |