Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Department of Pathology and Laboratory Medicine, |
RCV001354438 | SCV001549054 | likely pathogenic | Carcinoma of colon | no assertion criteria provided | clinical testing | The MLH1 p.Glu754LeufsX30 variant was not identified in the literature nor was it identified in the following databases: dbSNP, ClinVar, GeneInsight-COGR, Cosmic, MutDB, UMD-LSDB, Insight Colon Cancer, Zhejiang Colon Cancer, Mismatch Repair, or Insight Hereditary Tumors Database. 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.2258_2259dup variant is located in the last exon, three codons away from the termination codon (position 754) of the gene and extends the protein product 30 codons downstream. This alteration is then predicted to result in extension of the protein; although the consequence on protein function cannot be predicted, loss of function is possible. This variant was identified in one individual from our laboratory with colorectal cancer and with loss of the MLH1/PMS2 protein products in the tumour as determined by immunohistochemistry and with a strong family history of Lynch syndrome related cancers, increasing the likelihood this variant has clinical significance. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as likely pathogenic. |