Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000236662 | SCV000293667 | uncertain significance | not provided | 2015-12-08 | criteria provided, single submitter | clinical testing | This variant is denoted APC c.8075C>T at the cDNA level, p.Pro2692Leu (P2692L) at the protein level, and results in the change of a Proline to a Leucine (CCA>CTA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC Pro2692Leu was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Proline and Leucine differ in some properties, this is considered a semi-conservative amino acid substitution. APC Pro2692Leu occurs at a position that is not conserved and is not located within the EBI binding domain (Azzopardi 2008). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether APC Pro2692Leu is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. |
Ambry Genetics | RCV001027141 | SCV001189648 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-23 | criteria provided, single submitter | clinical testing | The p.P2692L variant (also known as c.8075C>T), located in coding exon 15 of the APC gene, results from a C to T substitution at nucleotide position 8075. The proline at codon 2692 is replaced by leucine, an amino acid with 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 | RCV003650550 | SCV001375064 | uncertain significance | Familial adenomatous polyposis 1 | 2023-11-02 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 2692 of the APC protein (p.Pro2692Leu). This variant is not present in population databases (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: 246208). 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. |