Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000477251 | SCV000551777 | uncertain significance | Colorectal cancer, hereditary nonpolyposis, type 7 | 2024-08-27 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 733 of the MLH3 protein (p.Leu733Val). This variant is present in population databases (rs566653064, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with MLH3-related conditions. ClinVar contains an entry for this variant (Variation ID: 410899). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The valine 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 | RCV004022849 | SCV002728595 | uncertain significance | not specified | 2023-07-09 | criteria provided, single submitter | clinical testing | The p.L733V variant (also known as c.2197T>G), located in coding exon 1 of the MLH3 gene, results from a T to G substitution at nucleotide position 2197. The leucine at codon 733 is replaced by valine, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species. 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. |