Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000075518 | SCV000106507 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | In frame large deletion interrupting functional domain |
Invitae | RCV000459146 | SCV000563810 | pathogenic | Lynch syndrome | 2016-09-30 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exon 3 of the MLH1 gene. This leads to an in-frame deletion, preserving the integrity of the reading frame. Similar in-frame deletions of exon 3 have been reported in two affected family members with Lynch syndrome, and in an individual affected with endometrial cancer (PMID: 8993976, 24323032). This in-frame deletion is expected to remove 33 amino acids (residues 70-102) from the ATPase domain of the MLH1 protein (PMID: 22753075). The deleted region contains conserved amino acids involved in ATP binding and hydrolysis, which are important for the mismatch repair activity of the MLH1 protein (PMID: 15475387, 11793442, 10199405, 9482749). For these reasons, this variant has been classified as Pathogenic. |