Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002538043 | SCV000949143 | uncertain significance | Familial adenomatous polyposis 1 | 2024-01-15 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 795 of the APC protein (p.Leu795Val). This variant is present in population databases (no rsID available, gnomAD no frequency). 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: 653265). 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. |
| Laboratory for Molecular Medicine, |
RCV000825285 | SCV000966578 | uncertain significance | not specified | 2018-10-18 | criteria provided, single submitter | clinical testing | The p.Leu795Val variant in APC has not been reported in individuals with APC-ass ociated polyposis conditions, but was identified in 1/250802 total chromosomes b y gnomAD (http://gnomad.broadinstitute.org). Computational prediction tools and conservation analysis suggest that the variant may not impact the protein. In su mmary, the clinical significance of the p.Leu795Val variant is uncertain. ACMG/A MP Criteria applied: BP4, PM2. |
| Ambry Genetics | RCV001015351 | SCV001176175 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-23 | criteria provided, single submitter | clinical testing | The p.L795V variant (also known as c.2383C>G), located in coding exon 15 of the APC gene, results from a C to G substitution at nucleotide position 2383. The leucine at codon 795 is replaced by valine, an amino acid with highly 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. |
| Color Diagnostics, |
RCV001015351 | SCV001358973 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-12-22 | criteria provided, single submitter | clinical testing | This missense variant replaces leucine with valine at codon 795 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 1/250802 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. |