Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000221872 | SCV000273875 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-06-10 | criteria provided, single submitter | clinical testing | The p.T1160I variant (also known as c.3479C>T), located in coding exon 15 of the APC gene, results from a C to T substitution at nucleotide position 3479. The threonine at codon 1160 is replaced by isoleucine, an amino acid with similar properties. This alteration has been identified in a cohort of 572 atherosclerosis patients with no clinical history of cancer (Pinard A et al. Hum Mutat, 2016 12;37:1299-1307). 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. |
| Color Diagnostics, |
RCV000221872 | SCV000686937 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-03-12 | criteria provided, single submitter | clinical testing | This missense variant replaces threonine with isoleucine at codon 1160 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 1/250788 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. |
| Invitae | RCV003534506 | SCV001201837 | uncertain significance | Familial adenomatous polyposis 1 | 2023-07-31 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 230352). 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. 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 0.003%). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 1160 of the APC protein (p.Thr1160Ile). |