Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV000775344 | SCV000909620 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-05 | criteria provided, single submitter | clinical testing | This missense variant replaces alanine with valine at codon 2257 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 been identified in 1/251010 chromosomes 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. |
Invitae | RCV003768386 | SCV002159348 | uncertain significance | Familial adenomatous polyposis 1 | 2021-07-30 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with valine at codon 2257 of the APC protein (p.Ala2257Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is present in population databases (rs762330941, ExAC 0.006%). ClinVar contains an entry for this variant (Variation ID: 630198). 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. 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. |
Ambry Genetics | RCV000775344 | SCV002661699 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-09-17 | criteria provided, single submitter | clinical testing | The p.A2257V variant (also known as c.6770C>T), located in coding exon 15 of the APC gene, results from a C to T substitution at nucleotide position 6770. The alanine at codon 2257 is replaced by valine, 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. |