Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001387815 | SCV001588534 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2020-01-23 | 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 not been reported in the literature in individuals with MSH6-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Cys1053Tyrfs*12) in the MSH6 gene. It is expected to result in an absent or disrupted protein product. |
| Ambry Genetics | RCV002322370 | SCV002610564 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-10-17 | criteria provided, single submitter | clinical testing | The c.3158_3159delGT pathogenic mutation, located in coding exon 4 of the MSH6 gene, results from a deletion of two nucleotides at nucleotide positions 3158 to 3159, causing a translational frameshift with a predicted alternate stop codon (p.C1053Yfs*12). This alteration has been observed in at least one individual with a personal and/or family history that is consistent with Lynch syndrome (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data available, 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. |
| Genetics and Molecular Pathology, |
RCV002466673 | SCV002761808 | pathogenic | Lynch syndrome 5 | 2022-05-26 | criteria provided, single submitter | clinical testing |