Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV000773630 | SCV000907324 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-04 | criteria provided, single submitter | clinical testing | This missense variant replaces valine with alanine at codon 2285 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 APC-related disorders 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. |
Ambry Genetics | RCV000773630 | SCV001187979 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-03 | criteria provided, single submitter | clinical testing | The p.V2285A variant (also known as c.6854T>C), located in coding exon 15 of the APC gene, results from a T to C substitution at nucleotide position 6854. The valine at codon 2285 is replaced by alanine, an amino acid with similar properties. This amino acid position is not 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 | RCV003653292 | SCV001395182 | uncertain significance | Familial adenomatous polyposis 1 | 2022-07-12 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 628963). 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 valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 2285 of the APC protein (p.Val2285Ala). |