Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003744541 | SCV000647782 | uncertain significance | Familial adenomatous polyposis 1 | 2020-05-25 | criteria provided, single submitter | clinical testing | In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. This sequence change replaces alanine with valine at codon 289 of the APC protein (p.Ala289Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a APC-related disease. |
Ambry Genetics | RCV002377121 | SCV002684441 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-05-17 | criteria provided, single submitter | clinical testing | The p.A289V variant (also known as c.866C>T), located in coding exon 8 of the APC gene, results from a C to T substitution at nucleotide position 866. The alanine at codon 289 is replaced by valine, an amino acid with 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. |