Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001016167 | SCV001177087 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-07 | criteria provided, single submitter | clinical testing | The p.R88L variant (also known as c.263G>T), located in coding exon 3 of the APC gene, results from a G to T substitution at nucleotide position 263. The arginine at codon 88 is replaced by leucine, 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. |
| Invitae | RCV003649194 | SCV001221544 | uncertain significance | Familial adenomatous polyposis 1 | 2019-12-17 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with APC-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with leucine at codon 88 of the APC protein (p.Arg88Leu). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and leucine. |
| Color Diagnostics, |
RCV001016167 | SCV001354862 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-04-07 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with leucine at codon 88 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). 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 not been identified 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. |