Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000575612 | SCV000667779 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-11-01 | criteria provided, single submitter | clinical testing | The p.I1418R variant (also known as c.4253T>G), located in coding exon 15 of the APC gene, results from a T to G substitution at nucleotide position 4253. The isoleucine at codon 1418 is replaced by arginine, an amino acid with similar properties. This amino acid position is well 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. |
Color Diagnostics, |
RCV000575612 | SCV000912512 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-17 | criteria provided, single submitter | clinical testing | This missense variant replaces isoleucine with arginine at codon 1418 of the APC protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 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 APC-related disorders 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. |
Invitae | RCV003476338 | SCV001544613 | uncertain significance | Familial adenomatous polyposis 1 | 2022-08-23 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 482503). This variant has not been reported in the literature in individuals affected with APC-related conditions. This sequence change replaces isoleucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1418 of the APC protein (p.Ile1418Arg). |
Baylor Genetics | RCV003476338 | SCV004202825 | uncertain significance | Familial adenomatous polyposis 1 | 2023-08-04 | criteria provided, single submitter | clinical testing |