Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000075035 | SCV000108256 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
Myriad Genetics, |
RCV003450992 | SCV004187349 | pathogenic | Lynch syndrome 5 | 2023-08-10 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation. |
Department of Pathology and Laboratory Medicine, |
RCV001354709 | SCV001549391 | pathogenic | Endometrial carcinoma | no assertion criteria provided | clinical testing | The MSH6 p.Ser252* variant was identified in 1 of 250 proband chromosomes (frequency: 0.004) from individuals or families with endometrial cancer (Devlin 2008). The variant was also identified in dbSNP (ID: rs267608048 as "With Pathogenic allele"), ClinVar (classified as pathogenic by InSiGHT), Mismatch Repair Genes Variant Database, and Insight Hereditary Tumors databases. The variant was not identified in Gene Insight-COGR, Cosmic, MutDB, UMD-LSDB, or Zhejiang University Database. The variant was not identified in the following control databases: the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project, the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The c.755C>G variant leads to a premature stop codon at position 252, which is predicted to lead to a truncated protein and loss of function. Loss of function variants of the MSH6 gene are an established mechanism of disease in MSH6-associated cancers 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. |