Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001010700 | SCV001170933 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-01-31 | criteria provided, single submitter | clinical testing | The p.A426T variant (also known as c.1276G>A), located in coding exon 9 of the APC gene, results from a G to A substitution at nucleotide position 1276. The alanine at codon 426 is replaced by threonine, an amino acid with similar properties. This variant has been detected in a Korean breast cancer patient (Park JS et al. BMC Cancer. 2018 Jan 16;18(1):83). 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. |
| Invitae | RCV003537390 | SCV003261083 | uncertain significance | Familial adenomatous polyposis 1 | 2022-09-03 | 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 C0"). ClinVar contains an entry for this variant (Variation ID: 818773). 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 alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 426 of the APC protein (p.Ala426Thr). |