Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001016178 | SCV001177098 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-03-18 | criteria provided, single submitter | clinical testing | The p.E878G variant (also known as c.2633A>G), located in coding exon 15 of the MSH2 gene, results from an A to G substitution at nucleotide position 2633. The glutamic acid at codon 878 is replaced by glycine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. 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. |
| Invitae | RCV001054059 | SCV001218352 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2023-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 878 of the MSH2 protein (p.Glu878Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Lynch syndrome (Invitae). ClinVar contains an entry for this variant (Variation ID: 821613). 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. This variant disrupts the p.Glu878 amino acid residue in MSH2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11208710, 18566915, 21778331, 21791569, 23523604, 25648859). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001284651 | SCV001470548 | uncertain significance | not provided | 2020-05-26 | criteria provided, single submitter | clinical testing |