Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000552597 | SCV000659595 | uncertain significance | Colorectal cancer, hereditary nonpolyposis, type 7 | 2017-07-20 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid with lysine at codon 1234 of the MLH3 protein (p.Glu1234Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MLH3-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, 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 | RCV004024423 | SCV002624132 | uncertain significance | not specified | 2024-05-08 | criteria provided, single submitter | clinical testing | The p.E1234K variant (also known as c.3700G>A), located in coding exon 6 of the MLH3 gene, results from a G to A substitution at nucleotide position 3700. The glutamic acid at codon 1234 is replaced by lysine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |