Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000781598 | SCV000919769 | likely pathogenic | Lynch syndrome | 2018-04-30 | criteria provided, single submitter | clinical testing | Variant summary: MSH6 c.2124_2126dupATA (p.Tyr709X) 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 (eg. c.2230dupG/p.Glu744fsX12, c.2731C>T/p.Arg911X). The variant was absent in 121150 control chromosomes. To our knowledge, no occurrence of c.2124_2126dupATA in individuals affected with Lynch Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Ambry Genetics | RCV002422672 | SCV002729937 | pathogenic | Hereditary cancer-predisposing syndrome | 2018-03-09 | criteria provided, single submitter | clinical testing | The c.2124_2126dupATA variant (also known as p.Y709*), located in coding exon 4 of the MSH6 gene, results from an in-frame duplication of ATA at nucleotide positions 2124 to 2126. This changes the amino acid from a tyrosine to a stop codon within coding exon 4. 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. |