Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Myriad Genetics, |
RCV003449413 | SCV004185786 | pathogenic | Lynch syndrome 5 | 2023-08-28 | 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. |
| Labcorp Genetics |
RCV003758803 | SCV004453009 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2024-10-16 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln1314*) in the MSH6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MSH6 are known to be pathogenic (PMID: 18269114, 24362816). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MSH6-related conditions. ClinVar contains an entry for this variant (Variation ID: 433929). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Department of Pathology and Laboratory Medicine, |
RCV000499819 | SCV000592662 | pathogenic | Carcinoma of colon | no assertion criteria provided | clinical testing | MSH6, EXON09, c.3940C>T, p.Gln1314*, Heterozygous, PathogenicrnThe MSH6 p.Gln1314* variant was not identified in the literature, nor was it identified in the dbSNP, NHLBI Exome Sequencing Project (Exome Variant Server), Exome Aggregation Consortium (ExAC), HGMD, COSMIC, MutDB, “Mismatch Repair Genes Variant Database”, “MMR Gene Unclassified Variants Database”, InSiGHT Colon Cancer Gene Variant Database, “Zhejiang Colon Cancer Database”, ClinVar, GeneInsight VariantWire or UMD. The p.Gln1314* variant leads to a premature stop codon at position 1314, which is predicted to lead to a truncated or absent protein and loss of function. Loss of function variants of the MSH6 gene are an established mechanism of disease in Lynch syndrome and this 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. Assessment Date: 2014/12/18. |