Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000491794 | SCV000580172 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-11-18 | criteria provided, single submitter | clinical testing | The c.3841_3847dupGAGACTA pathogenic mutation, located in coding exon 9 of the MSH6 gene, results from a duplication of GAGACTA at nucleotide position 3841, causing a translational frameshift with a predicted alternate stop codon (p.I1283Rfs*8). 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001844178 | SCV000695893 | likely pathogenic | Hereditary nonpolyposis colon cancer | 2022-02-15 | criteria provided, single submitter | clinical testing | Variant summary: MSH6 c.3841_3847dupGAGACTA (p.Ile1283ArgfsX8) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 250892 control chromosomes. To our knowledge, no occurrence of c.3841_3847dupGAGACTA in individuals affected with Hereditary Nonpolyposis Colorectal Cancer and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Myriad Genetics, |
RCV003449304 | SCV004185682 | pathogenic | Lynch syndrome 5 | 2023-08-25 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |
| Gene |
RCV004722829 | SCV005333383 | pathogenic | not provided | 2023-11-03 | criteria provided, single submitter | clinical testing | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Has not been previously published as pathogenic or benign to our knowledge |