Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001324571 | SCV001515528 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2023-10-28 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 451 of the MLH1 protein (p.Thr451Ala). 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: 219538). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MLH1 protein 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. |
Mayo Clinic Laboratories, |
RCV001507620 | SCV001713276 | uncertain significance | not provided | 2019-04-30 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002381702 | SCV002690048 | likely benign | Hereditary cancer-predisposing syndrome | 2020-02-06 | 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. |
All of Us Research Program, |
RCV003997567 | SCV004833272 | uncertain significance | Lynch syndrome | 2024-01-11 | criteria provided, single submitter | clinical testing |