Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000565584 | SCV000675939 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-05-26 | criteria provided, single submitter | clinical testing | Lines of evidence used in support of classification: Insufficient evidence |
| Color | RCV000565584 | SCV000686864 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-10-03 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000803070 | SCV000942928 | uncertain significance | Familial adenomatous polyposis 1 | 2018-12-03 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with glutamine at codon 623 of the APC protein (p.Arg623Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 486784). 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"). 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. 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. |