Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000807784 | SCV000947856 | uncertain significance | not provided | 2023-08-04 | criteria provided, single submitter | clinical testing | 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 output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The lysine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 652262). This variant has not been reported in the literature in individuals affected with MSH3-related conditions. This variant is present in population databases (rs747248456, gnomAD 0.006%). This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 573 of the MSH3 protein (p.Arg573Lys). |
| Ambry Genetics | RCV003166267 | SCV003856382 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-15 | criteria provided, single submitter | clinical testing | The p.R573K variant (also known as c.1718G>A), located in coding exon 12 of the MSH3 gene, results from a G to A substitution at nucleotide position 1718. The arginine at codon 573 is replaced by lysine, an amino acid with highly similar properties. This alteration was identified as heterozygous in the germline of a patient who met the WHO 2019 criteria for the diagnosis of Serrated polyposis syndrome (Hidaka M et al. BMC Res Notes, 2022 Nov;15:350). This amino acid position is well conserved in available vertebrate species; however, lysine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Baylor Genetics | RCV003461172 | SCV004197039 | uncertain significance | Endometrial carcinoma | 2023-10-11 | criteria provided, single submitter | clinical testing |