Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000236724 | SCV000293598 | uncertain significance | not provided | 2015-11-23 | criteria provided, single submitter | clinical testing | This variant is denoted APC c.7264A>C at the cDNA level, p.Thr2422Pro (T2422P) at the protein level, and results in the change of a Threonine to a Proline (ACT>CCT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC Thr2422Pro 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 Threonine and Proline differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. APC Thr2422Pro occurs at a position that is conserved in mammals and is not located in a known functional domain (Azzopardi 2008). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether APC Thr2422Pro is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. |
Invitae | RCV003650549 | SCV000951952 | uncertain significance | Familial adenomatous polyposis 1 | 2022-10-13 | 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: 246162). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces threonine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 2422 of the APC protein (p.Thr2422Pro). |
Color Diagnostics, |
RCV001804972 | SCV002052847 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-05-17 | criteria provided, single submitter | clinical testing | This missense variant replaces threonine with proline at codon 2422 of the APC protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, 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 1/250322 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. |
Baylor Genetics | RCV002518444 | SCV004205504 | uncertain significance | Familial adenomatous polyposis 1 | 2023-06-02 | criteria provided, single submitter | clinical testing |