Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001011631 | SCV001171975 | likely benign | Hereditary cancer-predisposing syndrome | 2024-12-02 | 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 |
RCV001210724 | SCV001382225 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2024-07-03 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 483 of the PMS2 protein (p.Asp483Asn). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 819241). 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 PMS2 protein 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. |
| Baylor Genetics | RCV003467596 | SCV004207797 | uncertain significance | Lynch syndrome 4 | 2023-07-05 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV005047204 | SCV005674325 | uncertain significance | Lynch syndrome 4; Mismatch repair cancer syndrome 4 | 2024-01-14 | criteria provided, single submitter | clinical testing |