Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003535606 | SCV000282730 | uncertain significance | Familial adenomatous polyposis 1 | 2023-07-07 | 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: 236585). This missense change has been observed in individual(s) with clinical features of breast and/or ovarian cancer (PMID: 31159747). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 1035 of the APC protein (p.Gln1035His). |
| Gene |
RCV000486957 | SCV000570553 | uncertain significance | not provided | 2016-06-02 | criteria provided, single submitter | clinical testing | This variant is denoted APC c.3105G>T at the cDNA level, p.Gln1035His (Q1035H) at the protein level, and results in the change of a Glutamine to a Histidine (CAG>CAT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC Gln1035His 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 Glutamine and Histidine differ in some properties, this is considered a semi-conservative amino acid substitution. APC Gln1035His occurs at a position that is not conserved and is located in the 15-amino acid repeat B-catenin binding domain and a region responsible for down-regulation through a process mediated by direct ubiquitination (Azzopardi 2008, UniProt). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether APC Gln1035His is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. |
| Gene |
RCV000708638 | SCV000821813 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-08-01 | criteria provided, single submitter | clinical testing |