Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003651895 | SCV000552763 | uncertain significance | Familial adenomatous polyposis 1 | 2023-10-03 | 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 548 of the APC protein (p.Leu548Val). This variant is present in population databases (no rsID available, gnomAD 0.0009%). 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: 411557). 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. |
| Ambry Genetics | RCV000565417 | SCV000672509 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-03-18 | criteria provided, single submitter | clinical testing | The p.L548V variant (also known as c.1642T>G), located in coding exon 13 of the APC gene, results from a T to G substitution at nucleotide position 1642. The leucine at codon 548 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. |
| Color Diagnostics, |
RCV000565417 | SCV000681481 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-11-20 | criteria provided, single submitter | clinical testing | This missense variant replaces leucine with valine at codon 548 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 APC-related disorders in the literature. This variant has been identified in 1/251176 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 |
RCV002291636 | SCV002584497 | uncertain significance | not provided | 2023-11-10 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Identified in an individual with malignant mesothelioma and family history of colorectal cancer (PMID: 34008015); This variant is associated with the following publications: (PMID: 18199528, 34008015) |