ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.3142C>T (p.Gln1048Ter) (rs200492211)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000202056 SCV000149310 pathogenic not provided 2018-06-20 criteria provided, single submitter clinical testing This pathogenic variant is denoted MSH6 c.3142C>T at the cDNA level and p.Gln1048Ter (Q1048X) at the protein level. The substitution creates a nonsense variant, changing a Glutamine to a premature stop codon (CAG>TAG). This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in at least one individual with colorectal cancer and one with endometrial cancer whose tumors showed loss of MSH6 via mismatch repair immunohistochemistry (Talseth-Palmer 2010, Buchanan 2014). Based on currently available evidence, we consider this variant to be pathogenic.
Ambry Genetics RCV000490956 SCV000580150 pathogenic Hereditary cancer-predisposing syndrome 2016-09-15 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000500240 SCV000592622 pathogenic Lynch syndrome 2015-09-01 criteria provided, single submitter clinical testing
Invitae RCV000544323 SCV000624821 pathogenic Hereditary nonpolyposis colon cancer 2018-12-13 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln1048*) in the MSH6 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with Lynch syndrome and colorectal and endometrial cancer (PMID: 20487569, 24323032, 27064304). ClinVar contains an entry for this variant (Variation ID: 127580). Loss-of-function variants in MSH6 are known to be pathogenic (PMID: 24362816, 18269114). For these reasons, this variant has been classified as Pathogenic.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000202056 SCV000257233 pathogenic not provided no assertion criteria provided research

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