Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000806152 | SCV000946134 | uncertain significance | Colorectal cancer, hereditary nonpolyposis, type 7 | 2018-11-06 | criteria provided, single submitter | clinical testing | 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. 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: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with MLH3-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with threonine at codon 541 of the MLH3 protein (p.Ile541Thr). The isoleucine residue is moderately conserved and there is a moderate physicochemical difference between isoleucine and threonine. |
| Ambry Genetics | RCV004028237 | SCV002704263 | uncertain significance | not specified | 2021-02-19 | criteria provided, single submitter | clinical testing | The p.I541T variant (also known as c.1622T>C), located in coding exon 1 of the MLH3 gene, results from a T to C substitution at nucleotide position 1622. The isoleucine at codon 541 is replaced by threonine, an amino acid with similar properties. This amino acid position is not well 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. |