Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001339336 | SCV001533070 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2021-08-26 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine with arginine at codon 62 of the MLH1 protein (p.Gln62Arg). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with MLH1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Experimental studies have shown that this missense change does not substantially affect MLH1 function (PMID: 15475387). 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. |
| Fulgent Genetics, |
RCV002476566 | SCV002783548 | uncertain significance | Mismatch repair cancer syndrome 1; Muir-Torré syndrome; Colorectal cancer, hereditary nonpolyposis, type 2 | 2022-04-09 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004035890 | SCV005033332 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-10-24 | criteria provided, single submitter | clinical testing | The p.Q62R variant (also known as c.185A>G), located in coding exon 2 of the MLH1 gene, results from an A to G substitution at nucleotide position 185. The glutamine at codon 62 is replaced by arginine, an amino acid with highly similar properties. A hybrid yeast-human experiment found that this variant had minimal impact on mismatch repair function (Ellison AR et al. Nucleic Acids Res, 2004 Oct;32:5321-38). This amino acid position is highly conserved in available vertebrate species. 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. |