Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV000777458 | SCV000913320 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-02-09 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000777458 | SCV001177620 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-12-30 | criteria provided, single submitter | clinical testing | The p.T934A variant (also known as c.2800A>G), located in coding exon 15 of the APC gene, results from an A to G substitution at nucleotide position 2800. The threonine at codon 934 is replaced by alanine, an amino acid with similar properties. In a study of whole-exome sequencing in patients with features of Cowden syndrome (CS) or Bannayan-Riley-Ruvalcaba syndrome (BRRS) and negative PTEN testing, this alteration was identified in 0/87 patients with CS or BRRS and 1/3476 patients from The Cancer Genome Atlas (TCGA) (Yehia L et al. PLoS Genet, 2018 04;14:e1007352). 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 | RCV002535615 | SCV001420334 | uncertain significance | Familial adenomatous polyposis 1 | 2024-01-18 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 934 of the APC protein (p.Thr934Ala). 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: 631285). 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. |
Prevention |
RCV003411715 | SCV004109587 | uncertain significance | APC-related condition | 2023-06-26 | criteria provided, single submitter | clinical testing | The APC c.2800A>G variant is predicted to result in the amino acid substitution p.Thr934Ala. This variant has been reported in an invasive breast carcinoma specimen from The Cancer Genome Atlas (TCGA; Table S9, Yehia et al. 2018. PubMed ID: 29684080). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. It is interpreted as uncertain significance in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/631285/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |