Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001043713 | SCV001207472 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2020-08-26 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in MSH6 are known to be pathogenic (PMID: 18269114, 24362816). This variant has been observed in a family affected with Lynch syndrome-related cancers (PMID: 25479140), as well as in an individual undergoing Lynch syndrome testing (PMID: 28514183). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Phe569Leufs*2) in the MSH6 gene. It is expected to result in an absent or disrupted protein product. |
| Ambry Genetics | RCV003307835 | SCV004006232 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-04-18 | criteria provided, single submitter | clinical testing | The c.1707delC pathogenic mutation, located in coding exon 4 of the MSH6 gene, results from a deletion of one nucleotide at nucleotide position 1707, causing a translational frameshift with a predicted alternate stop codon (p.F569Lfs*2). This alteration was identified amongst a cohort of 290 pancreatic ductal adenocarcinoma patients undergoing germline genetic testing (Grant RC et al. Gastroenterology, 2015 Mar;148:556-64). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Color Diagnostics, |
RCV003307835 | SCV004357610 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-06-13 | criteria provided, single submitter | clinical testing | This variant deletes 1 nucleotide in exon 4 of the MSH6 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in an individual affected with pancreatic ductal adenocarcinoma (PMID: 25479140). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of MSH6 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. |
| Department of Pathology and Laboratory Medicine, |
RCV001356817 | SCV001552084 | uncertain significance | not provided | no assertion criteria provided | clinical testing |