Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001234250 | SCV001406886 | uncertain significance | Colorectal cancer, hereditary nonpolyposis, type 7 | 2021-09-02 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with glycine at codon 1130 of the MLH3 protein (p.Asp1130Gly). The aspartic acid residue is weakly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with MLH3-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glycine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 | RCV004033232 | SCV002614569 | uncertain significance | not specified | 2024-09-20 | criteria provided, single submitter | clinical testing | The p.D1130G variant (also known as c.3389A>G), located in coding exon 3 of the MLH3 gene, results from an A to G substitution at nucleotide position 3389. The aspartic acid at codon 1130 is replaced by glycine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |