Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001233399 | SCV001405990 | uncertain significance | not provided | 2021-04-13 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine with leucine at codon 743 of the MSH3 protein (p.Gln743Leu). The glutamine residue is moderately conserved and there is a moderate physicochemical difference between glutamine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MSH3-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 | RCV004639516 | SCV005142079 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-05-27 | criteria provided, single submitter | clinical testing | The p.Q743L variant (also known as c.2228A>T), located in coding exon 15 of the MSH3 gene, results from an A to T substitution at nucleotide position 2228. The glutamine at codon 743 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |