Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Department of Pathology and Laboratory Medicine, |
RCV001358326 | SCV001554027 | pathogenic | Carcinoma of colon | no assertion criteria provided | clinical testing | The MLH1 c.1559-?_1667+?del variant (chr:3 g.37081677_37081785del GRCh37) results in a deletion of exon 14, however the precise breakpoints of this deletion were not determined, nor were the effects of this variant on the resulting mRNA or protein product. The MLH1 c.1559-?_1667+?del variant was identified in 1 of 384 proband chromosomes (frequency: 0.003) from individuals or families with Lynch syndrome (Di Fiore_2004). In addition this variant was identified in a single case in a study comparing detection of single exon deletions by MLPA and quantitative PCR (Vaughn 2008) The variant was also identified in ClinVar (2x, as pathogenic by InSight and Invitae), Clinvitae (2x, as pathogenic by ClinVar and Invitae), UMD-LSDB (1x, causal, pathogenic), Insight Colon Cancer Gene Variant Database (2x, as class 5), Insight Hereditary Tumors Database (2x, as class 5), databases. The variant was not identified in dbSNP, GeneInsight-COGR, Cosmic, MutDB, Zhejiang Colon Cancer Database, Mismatch Repair Genes Variant databases. The variant was not identified in the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project or the Exome Aggregation Consortium (August 8th 2016) control databases. The c.1559-?_1667+?del alteration is predicted to result in a truncated or absent protein and loss of function. Loss of function variants of the MLH1 gene are an established mechanism of disease in Lynch syndrome and is the type of variant expected to cause the disorder. In summary, based on the above information this variant meets our laboratory’s criteria to be classified as pathogenic. |