Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000129401 | SCV000184169 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-24 | criteria provided, single submitter | clinical testing | The p.M271V variant (also known as c.811A>G), located in coding exon 7 of the APC gene, results from an A to G substitution at nucleotide position 811. The methionine at codon 271 is replaced by valine, an amino acid with highly 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 | RCV003764864 | SCV000260249 | uncertain significance | Familial adenomatous polyposis 1 | 2023-07-25 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 271 of the APC protein (p.Met271Val). This variant is present in population databases (rs587781464, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 141061). 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. |
| Color Diagnostics, |
RCV000129401 | SCV000911729 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-10 | criteria provided, single submitter | clinical testing | This missense variant replaces methionine with valine at codon 271 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 3/282450 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. |
| Gene |
RCV001808396 | SCV002056068 | uncertain significance | not provided | 2023-07-11 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function |
| 3DMed Clinical Laboratory Inc | RCV000677764 | SCV000803920 | uncertain significance | Rectum adenocarcinoma | 2017-09-16 | no assertion criteria provided | clinical testing |