Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000684814 | SCV000548275 | likely benign | Hereditary nonpolyposis colorectal neoplasms | 2023-12-29 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000480593 | SCV000568619 | uncertain significance | not provided | 2019-09-18 | criteria provided, single submitter | clinical testing | Observed in individuals with suspected Lynch syndrome (Auclair 2006); Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 18383312, 16395668, 26951660, 26333163) |
| Ambry Genetics | RCV000565059 | SCV000669761 | likely benign | Hereditary cancer-predisposing syndrome | 2023-09-11 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: 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. |
| Color Diagnostics, |
RCV000565059 | SCV000685146 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-01-03 | criteria provided, single submitter | clinical testing | This missense variant replaces threonine with alanine at codon 33 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). This variant has been detected in a suspected Lynch syndrome family with two MLH1 covariants (PMID: 16395668). This variant has been identified in 3/222782 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 | RCV000076773 | SCV000837813 | uncertain significance | Lynch syndrome | 2018-07-02 | criteria provided, single submitter | clinical testing | |
| Genetic Services Laboratory, |
RCV001818242 | SCV002066925 | uncertain significance | not specified | 2017-12-22 | criteria provided, single submitter | clinical testing |