Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV001121869 | SCV001280524 | benign | Colorectal cancer, hereditary nonpolyposis, type 7 | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. |
Invitae | RCV001121869 | SCV002225095 | uncertain significance | Colorectal cancer, hereditary nonpolyposis, type 7 | 2023-04-07 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 741 of the MLH3 protein (p.Val741Ile). 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant  is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 888514). This variant has not been reported in the literature in individuals affected with MLH3-related conditions. This variant is present in population databases (rs28756990, gnomAD 0.04%), and has an allele count higher than expected for a pathogenic variant. |
Ambry Genetics | RCV002429768 | SCV002729688 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-06 | criteria provided, single submitter | clinical testing | The p.V741I variant (also known as c.2221G>A), located in coding exon 1 of the MLH3 gene, results from a G to A substitution at nucleotide position 2221. The valine at codon 741 is replaced by isoleucine, 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. |