Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000468451 | SCV000563811 | likely pathogenic | Lynch syndrome | 2016-05-03 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exons 7-10 of the MLH1 gene. This leads to an in-frame deletion, preserving the integrity of the reading frame. Truncating variants in MLH1 are known to be pathogenic. This particular truncation has been reported in the literature in individuals affected with Lynch syndrome (PMID: 11260232, 12494471, 15849733). This variant is expected to lead to an in-frame deletion of 112 amino acid residues from the MLH1 protein. Experimental studies investigating the functional impact of this deletion on the MLH1 protein have not been reported. However, a missense variant within this region (p.Val185Gly) has been observed in several families affected with Lynch Syndrome (PMID: 8808596, 16083711), and has been reported to disrupt MLH1 mismatch repair activity (PMID: 11781295, 21120944, 17510385), indicating that this region may be critical for protein function. In summary, this variant has been reported in affected individuals, and deletes a region important for MLH1 function. However, without additional functional and/or genetic data for this variant, it has been classified as Likely Pathogenic. |