Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002222863 | SCV002500073 | pathogenic | Hereditary nonpolyposis colon cancer | 2022-03-04 | criteria provided, single submitter | clinical testing | Variant summary: The variant identified by MLPA or other technology involves the duplication of exons 12-13 in the MLH1 gene. A presumed nomenclature of c.(1038+1_1039-1)_(1558+1_1559-1)dup has been designated for the purposes of this classification. It has been assumed that this is a tandem duplication in direct orientation (Richardson_GIM_2018, Newman_AJHG_2015). Although exact breakpoints of this duplication are not known, it is expected to result in a frameshift duplication change in the MLH1 gene, a known mechanism of disease. The variant was absent in 21694 control chromosomes (gnomAD, Structural Variants dataset). Duplication of exons 12-13 has been reported in the literature in multiple individuals/families affected with Lynch Syndrome (e.g. Alonso-Espinaco_2011, Ikenoue_2019). These data indicate that the variant is very likely to be associated with disease. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic. |