Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000461791 | SCV000551051 | uncertain significance | Hereditary nonpolyposis colon cancer | 2017-09-18 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with leucine at codon 1278 of the MSH6 protein (p.Pro1278Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MSH6-related disease. ClinVar contains an entry for this variant (Variation ID: 410394). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. |
| Ambry Genetics | RCV000491789 | SCV000580318 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-07-20 | criteria provided, single submitter | clinical testing | Lines of evidence used in support of classification: Insufficient evidence |