Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003650737 | SCV001391551 | uncertain significance | Familial adenomatous polyposis 1 | 2019-04-08 | criteria provided, single submitter | clinical testing | 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 aspartic acid with glycine at codon 1083 of the APC protein (p.Asp1083Gly). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. |
| Ambry Genetics | RCV002322062 | SCV002610988 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-04-23 | criteria provided, single submitter | clinical testing | The p.D1083G variant (also known as c.3248A>G), located in coding exon 15 of the APC gene, results from an A to G substitution at nucleotide position 3248. The aspartic acid at codon 1083 is replaced by glycine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |