Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001063167 | SCV001228002 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2023-11-10 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 329 of the MLH1 protein (p.His329Arg). 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: 857488). 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. |
| Gene |
RCV003229875 | SCV003927732 | uncertain significance | not provided | 2022-11-29 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 22753075) |
| Baylor Genetics | RCV003462595 | SCV004190631 | uncertain significance | Colorectal cancer, hereditary nonpolyposis, type 2 | 2023-08-30 | criteria provided, single submitter | clinical testing |