ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.1933del (p.Glu645fs)

dbSNP: rs1558663559
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000781581 SCV000919743 likely pathogenic Lynch syndrome 2018-03-14 criteria provided, single submitter clinical testing Variant summary: MSH6 c.1933delG (p.Glu645LysfsX3) 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.2150_2153delTCAG (p.Val717fsX18), c.2230dupG (p.Glu744fsX12), and c.2731C>T (p.Arg911X)). The variant was absent in 245904 control chromosomes (gnomAD). To our knowledge, no occurrence of c.1933delG 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.
Myriad Genetics, Inc. RCV003453613 SCV004187162 pathogenic Lynch syndrome 5 2023-08-16 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Baylor Genetics RCV004569491 SCV005055982 likely pathogenic Endometrial carcinoma 2023-11-07 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV004997309 SCV005623422 likely pathogenic not provided 2023-11-09 criteria provided, single submitter clinical testing The MSH6 c.1933del (p.Glu645Lysfs*3) variant alters the translational reading frame of the MSH6 mRNA and is predicted to cause the premature termination of MSH6 protein synthesis. This variant has not been reported in individuals with MSH6-related conditions in the published literature. This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Based on the available information, this variant is classified as likely pathogenic.

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