Total submissions: 10
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000203760 | SCV000260481 | likely benign | Hereditary nonpolyposis colorectal neoplasms | 2024-12-18 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000662969 | SCV000785948 | uncertain significance | Lynch syndrome 1 | 2018-01-18 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000771214 | SCV000903266 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-01-03 | criteria provided, single submitter | clinical testing | This missense variant replaces isoleucine with methionine at codon 169 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 1/251484 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. |
Mendelics | RCV000662969 | SCV001135704 | uncertain significance | Lynch syndrome 1 | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000771214 | SCV001185395 | likely benign | Hereditary cancer-predisposing syndrome | 2023-11-21 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Gene |
RCV001569238 | SCV001793277 | uncertain significance | not provided | 2019-08-29 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function |
Myriad Genetics, |
RCV000662969 | SCV004018277 | likely benign | Lynch syndrome 1 | 2023-03-17 | criteria provided, single submitter | clinical testing | This variant is considered likely benign. This variant is strongly associated with less severe personal and family histories of cancer, typical for individuals without pathogenic variants in this gene [PMID: 25085752]. |
Ce |
RCV001569238 | SCV004146068 | likely benign | not provided | 2023-12-01 | criteria provided, single submitter | clinical testing | MSH2: BP1, BP4 |
All of Us Research Program, |
RCV003997617 | SCV004830366 | uncertain significance | Lynch syndrome | 2024-03-05 | criteria provided, single submitter | clinical testing | This missense variant replaces isoleucine with methionine at codon 169 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 1/251484 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. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001569238 | SCV005623671 | uncertain significance | not provided | 2024-05-10 | criteria provided, single submitter | clinical testing | The MSH2 c.507A>G (p.Ile169Met) variant has been reported in the published literature in an individual with breast cancer (PMID: 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared/genes/MSH2). A published functional study reports that this variant is not damaging to protein function (PMID: 33357406 (2021)). The frequency of this variant in the general population, 0.000004 (1/251484 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |