Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000816617 | SCV000957134 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2022-02-21 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exon(s) 16 of the MLH1 gene. This variant would be expected to be in-frame, preserving the integrity of the reading frame. A similar copy number variant has been observed in individual(s) with Lynch syndrome (PMID: 7584969, 8776590, 9833759, 10200055, 12919140, 14574010, 15942939). It has also been observed to segregate with disease in related individuals. Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that a similar copy number variant affects MLH1 function (PMID: 9697702, 11793442). This variant disrupts the p.Lys618 amino acid residue in MLH1. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |