Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000221003 | SCV000273577 | uncertain significance | Hereditary cancer-predisposing syndrome | 2016-06-23 | criteria provided, single submitter | clinical testing | Lines of evidence used in support of classification: Insufficient or conflicting evidence |
Invitae | RCV000688104 | SCV000815704 | uncertain significance | Hereditary nonpolyposis colon cancer | 2018-04-06 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine with threonine at codon 359 of the MLH1 protein (p.Met359Thr). The methionine residue is weakly conserved and there is a moderate physicochemical difference between methionine and threonine. This variant is present in population databases (rs779917781, ExAC 0.002%). This variant has not been reported in the literature in individuals with MLH1-related disease. ClinVar contains an entry for this variant (Variation ID: 230138). 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |