Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000219275 | SCV000278543 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-13 | criteria provided, single submitter | clinical testing | The p.L2539F variant (also known as c.7615C>T), located in coding exon 15 of the APC gene, results from a C to T substitution at nucleotide position 7615. The leucine at codon 2539 is replaced by phenylalanine, 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. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000508556 | SCV000600156 | uncertain significance | not specified | 2016-09-29 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000219275 | SCV000904814 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-04 | criteria provided, single submitter | clinical testing | This missense variant replaces leucine with phenylalanine at codon 2539 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 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 | RCV003535594 | SCV001416953 | uncertain significance | Familial adenomatous polyposis 1 | 2023-02-01 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 234053). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 2539 of the APC protein (p.Leu2539Phe). |
Baylor Genetics | RCV002516177 | SCV004198137 | uncertain significance | Familial adenomatous polyposis 1 | 2023-10-17 | criteria provided, single submitter | clinical testing |