Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001071073 | SCV001236357 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2023-06-14 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 827 of the MSH2 protein (p.Gly827Arg). This variant is not present in population databases (gnomAD no frequency). 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. This variant disrupts the p.Gly827 amino acid residue in MSH2. Other variant(s) that disrupt this residue have been observed in individuals with MSH2-related conditions (PMID: 32933947), which suggests that this may be a clinically significant amino acid residue. Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 33357406) indicates that this missense variant is not expected to disrupt MSH2 function. ClinVar contains an entry for this variant (Variation ID: 863985). This missense change has been observed in individual(s) with uterine cancer (Invitae). |
| Ambry Genetics | RCV002445368 | SCV002734640 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-05-27 | criteria provided, single submitter | clinical testing | The p.G827R variant (also known as c.2479G>A), located in coding exon 15 of the MSH2 gene, results from a G to A substitution at nucleotide position 2479. The glycine at codon 827 is replaced by arginine, an amino acid with dissimilar properties. Using a Bayesian analysis that incorporates tumor mutation data, this variant was classified as a variant of uncertain significance (Shirts BH et al. Am J Hum Genet, 2018 07;103:19-29). 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. |