Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV004048242 | SCV002624778 | uncertain significance | not specified | 2024-09-16 | criteria provided, single submitter | clinical testing | The p.E1288A variant (also known as c.3863A>C), located in coding exon 8 of the MLH3 gene, results from an A to C substitution at nucleotide position 3863. The glutamic acid at codon 1288 is replaced by alanine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Labcorp Genetics |
RCV003614113 | SCV004517127 | uncertain significance | Colorectal cancer, hereditary nonpolyposis, type 7 | 2023-04-01 | 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. 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 disruptive. ClinVar contains an entry for this variant (Variation ID: 1735625). This variant has not been reported in the literature in individuals affected with MLH3-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 1288 of the MLH3 protein (p.Glu1288Ala). |