Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000217983 | SCV000273702 | likely benign | Hereditary cancer-predisposing syndrome | 2022-03-22 | 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. |
| Labcorp Genetics |
RCV000537839 | SCV000625258 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2025-01-08 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 466 of the MSH2 protein (p.His466Tyr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MSH2-related conditions. ClinVar contains an entry for this variant (Variation ID: 230236). Invitae Evidence Modeling incorporating data from in vitro experimental studies (PMID: 33357406) indicates that this missense variant is not expected to disrupt MSH2 function with a negative predictive value of 95%. 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. |
| Color Diagnostics, |
RCV000217983 | SCV000903694 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-08-25 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001589141 | SCV001822654 | uncertain significance | not provided | 2020-12-07 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); 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 |