Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001203440 | SCV001374606 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2021-10-28 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 40 of the MSH2 protein (p.Gly40Asp). 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. 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 934948). This variant has not been reported in the literature in individuals affected with MSH2-related conditions. |
| Ambry Genetics | RCV002348659 | SCV002645035 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-06-25 | criteria provided, single submitter | clinical testing | The p.G40D variant (also known as c.119G>A), located in coding exon 1 of the MSH2 gene, results from a G to A substitution at nucleotide position 119. The glycine at codon 40 is replaced by aspartic acid, an amino acid with similar properties. This amino acid position is not 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. |