Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002834434 | SCV003214370 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2022-09-04 | criteria provided, single submitter | clinical testing | 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 expected to disrupt MLH1 protein function. This variant has not been reported in the literature in individuals affected with MLH1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 548 of the MLH1 protein (p.Tyr548Cys). 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. |
All of Us Research Program, |
RCV004007634 | SCV004839328 | uncertain significance | Lynch syndrome | 2023-12-01 | criteria provided, single submitter | clinical testing |