Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001027003 | SCV001189489 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-09-01 | criteria provided, single submitter | clinical testing | The p.I265M variant (also known as c.795T>G), located in coding exon 5 of the MSH3 gene, results from a T to G substitution at nucleotide position 795. The isoleucine at codon 265 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is highly 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. |
| Labcorp Genetics |
RCV002551990 | SCV003522088 | uncertain significance | not provided | 2023-12-02 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 265 of the MSH3 protein (p.Ile265Met). This variant is present in population databases (rs765814546, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with MSH3-related conditions. ClinVar contains an entry for this variant (Variation ID: 827360). 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. 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. |