Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000076892 | SCV000108385 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | In-frame large deletion interrupting ATPase domain [pmid:11574484 Guarne:2001] |
Invitae | RCV000076892 | SCV000299097 | pathogenic | Lynch syndrome | 2016-10-05 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exons 8-11 of the PMS2 gene. This leads to an in-frame deletion, preserving the integrity of the reading frame. Deletions of exons 8-11 have been reported in individuals affected with Lynch Syndrome (PMID: 8072530, 25980754). The tumor from one patient exhibited microsatellite instability and acquired a second mutation on the wild-type allele (PMID: 8072530). Experimental studies have shown that this deletion removes a coiled-coil domain in PMS2 that mediates the interaction with MLH1 (PMID: 11292842). For these reasons, this variant has been classified as Pathogenic. |