Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001322112 | SCV001512969 | uncertain significance | not provided | 2023-06-29 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. ClinVar contains an entry for this variant (Variation ID: 1022228). This variant has not been reported in the literature in individuals affected with MSH3-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 359 of the MSH3 protein (p.Ile359Leu). |
| Ambry Genetics | RCV004651583 | SCV005141971 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-03-23 | criteria provided, single submitter | clinical testing | The p.I359L variant (also known as c.1075A>C), located in coding exon 7 of the MSH3 gene, results from an A to C substitution at nucleotide position 1075. The isoleucine at codon 359 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear. |