ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.4081T>C (p.Ter1361Gln) (rs765098678)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000486271 SCV000565243 uncertain significance not provided 2015-08-25 criteria provided, single submitter clinical testing This variant is denoted MSH6 c.4081T>C at the cDNA level and p.Ter1361GlnextX29 (X1361QextX29) at the protein level. This substitution is located in the stop codon of the MSH6 gene and results in the natural stop codon being changed to a Glutamine (TAG>CAG), resulting in the extension of the protein by 29 amino acids. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. Of note, this variant is in the C-terminal region of MSH6 which is a binding site for MSH2 (Kariola 2002). Based on currently available information, it is unclear whether MSH6 Ter1361GlnextX29 is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000562452 SCV000676113 uncertain significance Hereditary cancer-predisposing syndrome 2018-04-19 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,Co-occurence with a mutation in another gene that clearly explains a proband's phenotype
Invitae RCV000694136 SCV000822567 uncertain significance Hereditary nonpolyposis colon cancer 2018-09-03 criteria provided, single submitter clinical testing This sequence change disrupts the translational stop signal of the MSH6 mRNA. It is expected to extend the length of the MSH6 protein by 29 additional amino acid residues. This variant is present in population databases (rs765098678, ExAC 0.006%). This variant has not been reported in the literature in individuals with MSH6-related disease. ClinVar contains an entry for this variant (Variation ID: 418334). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Color RCV000562452 SCV000908446 uncertain significance Hereditary cancer-predisposing syndrome 2018-03-23 criteria provided, single submitter clinical testing

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