Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002232030 | SCV000647661 | uncertain significance | Familial adenomatous polyposis 1 | 2021-11-02 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 2226 of the APC protein (p.Arg2226Gln). 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: 470058). 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: "Probably Damaging"; Align-GVGD: "Class C0"). 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. |
Ambry Genetics | RCV001025521 | SCV001187723 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-03-23 | criteria provided, single submitter | clinical testing | The p.R2226Q variant (also known as c.6677G>A), located in coding exon 15 of the APC gene, results from a G to A substitution at nucleotide position 6677. The arginine at codon 2226 is replaced by glutamine, an amino acid with highly similar 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. |
Prevention |
RCV003900204 | SCV004712853 | uncertain significance | APC-related condition | 2023-11-08 | criteria provided, single submitter | clinical testing | The APC c.6677G>A variant is predicted to result in the amino acid substitution p.Arg2226Gln. To our knowledge, this variant has not been reported in the literature or 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/470058/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |