Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000573561 | SCV000676058 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-02-08 | criteria provided, single submitter | clinical testing | Lines of evidence used in support of classification: Insufficient evidence |
Invitae | RCV000808793 | SCV000948914 | uncertain significance | Hereditary nonpolyposis colon cancer | 2018-12-05 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with methionine at codon 404 of the MLH1 protein (p.Leu404Met). The leucine residue is weakly conserved and there is a small physicochemical difference between leucine and methionine. 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: 486862). 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. |