Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003225727 | SCV000552725 | uncertain significance | Familial adenomatous polyposis 1 | 2023-08-14 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1140 of the APC protein (p.Pro1140Arg). This variant is present in population databases (no rsID available, gnomAD 0.006%). 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: 411525). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on APC protein function. 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. |
| Color Diagnostics, |
RCV000582714 | SCV000686933 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-01-16 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with arginine at codon 1140 of the APC protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 2/250948 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. |
| Ambry Genetics | RCV000582714 | SCV001181707 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-03 | criteria provided, single submitter | clinical testing | The p.P1140R variant (also known as c.3419C>G), located in coding exon 15 of the APC gene, results from a C to G substitution at nucleotide position 3419. The proline at codon 1140 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Laboratorio de Genetica e Diagnostico Molecular, |
RCV003225727 | SCV003807738 | uncertain significance | Familial adenomatous polyposis 1 | 2023-01-20 | criteria provided, single submitter | clinical testing | ACMG classification criteria: PM2 supporting, PP3 supporting |
| Baylor Genetics | RCV003225727 | SCV004201524 | uncertain significance | Familial adenomatous polyposis 1 | 2023-07-13 | criteria provided, single submitter | clinical testing |