Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003743706 | SCV000647262 | uncertain significance | Familial adenomatous polyposis 1 | 2022-08-16 | criteria provided, single submitter | clinical testing | 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: "Benign"; Align-GVGD: "Class C15"). ClinVar contains an entry for this variant (Variation ID: 374938). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is present in population databases (rs746393911, gnomAD 0.0009%). This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 908 of the APC protein (p.Ser908Cys). |
Color Diagnostics, |
RCV001178072 | SCV001342404 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-07-03 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with cysteine at codon 908 of the APC protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/251040 chromosomes in the general population by the Genome Aggregation Database (gnomAD). 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. |
Ambry Genetics | RCV001178072 | SCV002741465 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-09-23 | criteria provided, single submitter | clinical testing | The p.S908C variant (also known as c.2723C>G), located in coding exon 15 of the APC gene, results from a C to G substitution at nucleotide position 2723. The serine at codon 908 is replaced by cysteine, 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. |
Knight Diagnostic Laboratories, |
RCV000415716 | SCV000493708 | uncertain significance | Familial adenomatous polyposis 1 | 2015-09-26 | no assertion criteria provided | clinical testing |