Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001014531 | SCV001175249 | likely benign | Hereditary cancer-predisposing syndrome | 2019-05-22 | 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 |
RCV001220133 | SCV001392107 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2024-10-20 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 708 of the MLH1 protein (p.Ile708Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MLH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 820762). Invitae Evidence Modeling incorporating data from in vitro experimental studies (internal data) indicates that this missense variant is not expected to disrupt MLH1 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. |
| Baylor Genetics | RCV004569934 | SCV005057972 | uncertain significance | Colorectal cancer, hereditary nonpolyposis, type 2 | 2024-02-23 | criteria provided, single submitter | clinical testing |