Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001547084 | SCV001766707 | uncertain significance | not provided | 2019-05-24 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge |
Ambry Genetics | RCV002440785 | SCV002747174 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-06-25 | criteria provided, single submitter | clinical testing | The p.V923I variant (also known as c.2767G>A), located in coding exon 16 of the MSH2 gene, results from a G to A substitution at nucleotide position 2767. The valine at codon 923 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is well 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. |
All of Us Research Program, |
RCV004008925 | SCV004829420 | uncertain significance | Lynch syndrome | 2023-07-13 | criteria provided, single submitter | clinical testing | This missense variant replaces valine with isoleucine at codon 923 of the MSH2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). This variant does not impact MSH2 function in a 6-thioguanine sensitivity assay in haploid human cells (internally defined LOF score threshold <= -1.32, PMID: 33357406). To our knowledge, this variant has not been reported in individuals affected with MSH2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |