Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000630434 | SCV000751390 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2018-01-08 | criteria provided, single submitter | clinical testing | This variant is an in-frame deletion of the genomic region encompassing exons 2-7 of the MSH2 gene. It preserves the integrity of the reading frame. Deletions of exons 2-7 have been reported in individuals and families affected with Lynch syndrome (PMID: 15942939, 21642682, 20587412, 16541406). ClinVar contains an entry for this deletion (Variation ID: 90896). Deletions of exons 2-7 eliminate the entire connector domain, which is encoded by exons 3-5 of the MSH2 mRNA. The connector domain is required for mismatch repair (MMR) complex formation, which is necessary for adequate MSH2 mismatch repair protein function (PMID: 18822302, 18383312, 20080788, 26163658, 21454657). For these reasons, this variant has been classified as Pathogenic. |