ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.3463C>T (p.Gln1155Ter) (rs1553332166)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000568670 SCV000670065 pathogenic Hereditary cancer-predisposing syndrome 2017-03-30 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)
Integrated Genetics/Laboratory Corporation of America RCV000780477 SCV000917761 likely pathogenic Lynch syndrome 2018-05-14 criteria provided, single submitter clinical testing Variant summary: MSH6 c.3463C>T (p.Gln1155X) 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 (e.g. c.3476dupA (p.Tyr1159X), c.3513_3514delTA (p.Asp1171fsX5), c.3514dupA (p.Arg1172fsX5)). The variant was absent in 246166 control chromosomes. c.3463C>T has been reported in the literature in an individual with bladder cancer (Mandelker 2017). This report does not provide unequivocal conclusions about association of the variant with Lynch Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.

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