Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV000580000 | SCV000681475 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-01 | criteria provided, single submitter | clinical testing | This missense variant replaces methionine with valine at codon 526 of the APC protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 3/282328 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 | RCV003537217 | SCV000954701 | uncertain significance | Familial adenomatous polyposis 1 | 2023-11-14 | 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 526 of the APC protein (p.Met526Val). This variant is present in population databases (rs777219286, 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: 489416). 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 with a negative predictive value of 95%. 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 | RCV000580000 | SCV001172668 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-07-29 | criteria provided, single submitter | clinical testing | The p.M526V variant (also known as c.1576A>G), located in coding exon 12 of the APC gene, results from an A to G substitution at nucleotide position 1576. The methionine at codon 526 is replaced by valine, an amino acid with highly similar properties. 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. |
Sema4, |
RCV000580000 | SCV002527667 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-08-19 | criteria provided, single submitter | curation | |
3DMed Clinical Laboratory Inc | RCV000677751 | SCV000803907 | uncertain significance | Neoplasm of the liver | 2017-06-28 | no assertion criteria provided | clinical testing |