Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003742602 | SCV000647227 | uncertain significance | Familial adenomatous polyposis 1 | 2017-05-11 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a APC-related disease. This sequence change replaces leucine with proline at codon 75 of the APC protein (p.Leu75Pro). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and proline. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV001014931 | SCV001175704 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-11-16 | criteria provided, single submitter | clinical testing | The p.L75P variant (also known as c.224T>C), located in coding exon 3 of the APC gene, results from a T to C substitution at nucleotide position 224. The leucine at codon 75 is replaced by proline, an amino acid with 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. |