Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000215154 | SCV000273564 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-01-12 | criteria provided, single submitter | clinical testing | The p.V569M variant (also known as c.1705G>A), located in coding exon 13 of the APC gene, results from a G to A substitution at nucleotide position 1705. The valine at codon 569 is replaced by methionine, an amino acid with highly similar properties. In a cohort of 300 deceased patients, who underwent whole genome sequencing for 60 autosomal dominant cancer predisposition genes, this variant was detected and classified as "unknown significance" by the authors. However, the specific phenotype of the patient(s) with this alteration was not reported (He KY et al. PLoS One, 2016 Dec;11:e0167847). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Color Diagnostics, |
RCV000215154 | SCV000914016 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-24 | criteria provided, single submitter | clinical testing | This missense variant replaces valine with methionine at codon 569 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 been reported in an individual undergoing testing for familial adenomatous polyps (PMID: 23159591). 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. |
| Invitae | RCV003650476 | SCV001202238 | uncertain significance | Familial adenomatous polyposis 1 | 2022-12-29 | criteria provided, single submitter | clinical testing | Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt APC protein function. 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. ClinVar contains an entry for this variant (Variation ID: 230127). This missense change has been observed in individual(s) with clinical features of familial adenomatous polyposis (PMID: 23159591). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 569 of the APC protein (p.Val569Met). |
| Baylor Genetics | RCV002518259 | SCV004202736 | uncertain significance | Familial adenomatous polyposis 1 | 2023-08-06 | criteria provided, single submitter | clinical testing |