Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003651972 | SCV000647547 | uncertain significance | Familial adenomatous polyposis 1 | 2022-04-25 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs748715887, gnomAD 0.0009%). This sequence change replaces cysteine, which is neutral and slightly polar, with phenylalanine, which is neutral and non-polar, at codon 1643 of the APC protein (p.Cys1643Phe). 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: 469983). 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 | RCV002341385 | SCV002641158 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-06 | criteria provided, single submitter | clinical testing | The p.C1643F variant (also known as c.4928G>T), located in coding exon 15 of the APC gene, results from a G to T substitution at nucleotide position 4928. The cysteine at codon 1643 is replaced by phenylalanine, an amino acid with highly 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. |