Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000532242 | SCV000625255 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2023-10-31 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 456 of the MSH2 protein (p.Thr456Ile). This variant is present in population databases (rs777963115, gnomAD 0.0009%). 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: 455485). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 33357406) indicates that this missense variant is not expected to disrupt MSH2 function with a negative predictive value of 80%. 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. |
Ambry Genetics | RCV000562767 | SCV000669852 | likely benign | Hereditary cancer-predisposing syndrome | 2023-01-13 | 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. |
Color Diagnostics, |
RCV000562767 | SCV000684932 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-06-12 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV004003732 | SCV004831062 | uncertain significance | Lynch syndrome | 2023-08-15 | criteria provided, single submitter | clinical testing |