Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000470591 | SCV000548189 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2019-03-21 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with MSH2-related conditions. ClinVar contains an entry for this variant (Variation ID: 408489). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamine with proline at codon 339 of the MSH2 protein (p.Gln339Pro). The glutamine residue is highly conserved and there is a moderate physicochemical difference between glutamine and proline. |
| Gene |
RCV004794390 | SCV005414687 | uncertain significance | not provided | 2024-05-24 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 18822302, 21120944) |
| Ambry Genetics | RCV004943895 | SCV005450595 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-08-14 | criteria provided, single submitter | clinical testing | The p.Q339P variant (also known as c.1016A>C), located in coding exon 6 of the MSH2 gene, results from an A to C substitution at nucleotide position 1016. The glutamine at codon 339 is replaced by proline, an amino acid with similar properties. This variant’s functional status was inconclusive in a massively parallel cell-based functional assay testing susceptibility to a DNA damaging agent, 6-thioguanine (6-TG) (Jia X et al. Am J Hum Genet, 2021 Jan;108:163-175). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |