Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001031922 | SCV001195229 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2019-04-10 | criteria provided, single submitter | clinical testing | This variant is an in-frame deletion of the genomic region encompassing exons 17-18 of the MLH1 gene. It preserves the integrity of the reading frame. Similar deletion of exons 17-18 has not been reported in the literature in individuals with MLH1-related conditions. This variant disrupts the C-terminal PMS2 interaction domain of the MLH1 protein, which is necessary for proper MLH1-PMS2 dimerization and normal protein functioning (PMID: 10037723, 11793442, 16083711). This suggests that disruption of this region of the protein is causative of disease. For these reasons, this variant has been classified as Pathogenic. |