Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003742769 | SCV000647665 | uncertain significance | Familial adenomatous polyposis 1 | 2018-08-12 | criteria provided, single submitter | clinical testing | 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 470061). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with valine at codon 225 of the APC protein (p.Glu225Val). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and valine. |
Ambry Genetics | RCV001025610 | SCV001187835 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-10-28 | criteria provided, single submitter | clinical testing | The p.E225V variant (also known as c.674A>T), located in coding exon 6 of the APC gene, results from an A to T substitution at nucleotide position 674. The glutamic acid at codon 225 is replaced by valine, an amino acid with 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. |