Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000534549 | SCV000625146 | uncertain significance | Hereditary nonpolyposis colon cancer | 2017-06-09 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with glycine at codon 106 of the MLH1 protein (p.Ser106Gly). The serine residue is highly conserved and there is a small physicochemical difference between serine 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 an MLH1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, this variant has uncertain impact on MLH1 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV000564403 | SCV000669589 | uncertain significance | Hereditary cancer-predisposing syndrome | 2016-11-18 | criteria provided, single submitter | clinical testing | Lines of evidence used in support of classification: In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Insufficient evidence |