Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000534285 | SCV000624569 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2017-07-13 | criteria provided, single submitter | clinical testing | This variant is an in-frame deletion of the genomic region encompassing exons 3-4 of the MSH2 gene. It preserves the integrity of the reading frame. While the deletion of exon 3-4 has not been reported in the literature, deletions of exon 3 and of exon 4 which are also in-frame deletions have been reported in individuals and families with Lynch syndrome (PMID: 19459153, 21642682, 16541406, 22883484, 9843200, 10480359, 14512394, 18566915). Furthermore, Deletion of exons 3 and 4 (p.Ala123_Gln264del) removes the connector domain (or DNA binding domain) of the MSH2 protein. 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. |