Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002421926 | SCV002725580 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-07-14 | criteria provided, single submitter | clinical testing | The c.2059dupT pathogenic mutation, located in coding exon 4 of the MSH6 gene, results from a duplication of T at nucleotide position 2059, causing a translational frameshift with a predicted alternate stop codon (p.C687Lfs*11). This variant has been identified in a proband whose Lynch syndrome-associated tumor demonstrated high microsatellite instability and loss of MSH6 expression by immunohistochemistry (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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. |
| Baylor Genetics | RCV003465750 | SCV004195657 | pathogenic | Endometrial carcinoma | 2023-07-14 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV003759708 | SCV004455594 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2024-12-16 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Cys687Leufs*11) 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: 1785177). For these reasons, this variant has been classified as Pathogenic. |