Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000563609 | SCV000669609 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-05-08 | criteria provided, single submitter | clinical testing | Insufficient evidence |
| Invitae | RCV001217551 | SCV001389397 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2019-06-14 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with glycine at codon 498 of the MLH1 protein (p.Arg498Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MLH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 483585). 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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). 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. |