Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000798634 | SCV000938259 | uncertain significance | Colorectal cancer, hereditary nonpolyposis, type 7 | 2025-02-03 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ser466*) in the MLH3 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in MLH3 cause disease. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Lynch syndrome whom also carried a pathogenic variant in MLH1 (PMID: 30614234). ClinVar contains an entry for this variant (Variation ID: 644666). 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. |