Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001208473 | SCV001379864 | uncertain significance | not provided | 2023-11-30 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 655 of the MSH3 protein (p.Ile655Thr). This variant is present in population databases (no rsID available, gnomAD 0.002%). 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: 939131). 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 tolerated. 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. |
| Ambry Genetics | RCV002418701 | SCV002722236 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-27 | criteria provided, single submitter | clinical testing | The p.I655T variant (also known as c.1964T>C), located in coding exon 14 of the MSH3 gene, results from a T to C substitution at nucleotide position 1964. The isoleucine at codon 655 is replaced by threonine, an amino acid with similar properties. This amino acid position is poorly 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. |
| Baylor Genetics | RCV003462696 | SCV004197025 | uncertain significance | Endometrial carcinoma | 2023-12-01 | criteria provided, single submitter | clinical testing |