Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000702160 | SCV000831001 | likely benign | Hereditary nonpolyposis colorectal neoplasms | 2024-01-03 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV001175679 | SCV001339369 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-23 | criteria provided, single submitter | clinical testing | This missense variant replaces isoleucine with methionine at codon 192 of the MSH2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, 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 been identified in 1/251432 chromosomes 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. |
Ambry Genetics | RCV001175679 | SCV002650748 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-07-13 | criteria provided, single submitter | clinical testing | The p.I192M variant (also known as c.576C>G), located in coding exon 3 of the MSH2 gene, results from a C to G substitution at nucleotide position 576. The isoleucine at codon 192 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is not 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. |
Baylor Genetics | RCV003460973 | SCV004196930 | uncertain significance | Lynch syndrome 1 | 2021-10-21 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV003999726 | SCV004828444 | uncertain significance | Lynch syndrome | 2023-09-04 | criteria provided, single submitter | clinical testing | This missense variant replaces isoleucine with methionine at codon 192 of the MSH2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, 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 been identified in 1/251432 chromosomes 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. |