Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003653236 | SCV000768043 | uncertain significance | Familial adenomatous polyposis 1 | 2020-06-09 | 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: "Possibly Damaging"; Align-GVGD: "Class C0"). This sequence change replaces glutamine with glutamic acid at codon 195 of the APC protein (p.Gln195Glu). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and glutamic acid. This variant is present in population databases (rs749479682, ExAC 0.01%). This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 537423). |
Ambry Genetics | RCV002358843 | SCV002650844 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-06-24 | criteria provided, single submitter | clinical testing | The p.Q195E variant (also known as c.583C>G), located in coding exon 5 of the APC gene, results from a C to G substitution at nucleotide position 583. The glutamine at codon 195 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is highly 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. |