ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1786_1790delinsGG (p.Asn596_Asp597delinsGly) (rs1558517764)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000780436 SCV000917684 uncertain significance not specified 2018-03-28 criteria provided, single submitter clinical testing Variant summary: MSH2 c.1786_1790delinsGG (p.Asn596_Asp597delinsGly) results in an in-frame deletion/insertion that removes the Asn596 and Asp597 amino acids and replaces them with a Gly located in the DNA mismatch repair protein MutS, core domain (InterPro). The variant was absent in 246242 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1786_1790delinsGG in individuals affected with HNPCC and no experimental evidence demonstrating its impact on protein function have been reported. However, a different variant affecting this position and also leading to an in frame deletion (c.1786_1788delAAT, p.Asn596del) is classified as pathogenic in ClinVar by several laboratories, as it has been shown to segregate with Lynch syndrome and Asn596del has been demonstrated to result in a functionally impaired protein in several studies. These reports might indicate the importance of this region for protein function. 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 uncertain significance.

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