Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000551811 | SCV000624576 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2017-03-09 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exons 14-16 of the MSH2 gene. The 5' boundary is likely confined to intron 13. The 3' end of this event is unknown as it extends through the termination codon beyond the assayed region for this gene and may encompass additional genes. While this deletion is not anticipated to result in nonsense mediated decay, it is expected to create a truncated protein product or disrupt mRNA translation. Loss-of-function variants in MSH2 are known to be pathogenic. A deletion of MSH2 exons 14-16 has been reported in the literature in an individual affected with Lynch sydrome (PMID: 25430799). While this variant is not anticipated to result in nonsense mediated decay, it is expected to delete the last 197 amino acids of the MSH2 protein (Ser738-Thr934). This will remove most of the ATPase domain and all of the helix-turn-helix domain, both of which are important for MSH2 protein function (PMID: 18822302). For these reasons, this variant has been classified as Pathogenic. |