ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1429A>C (p.Asn477His) (rs587781346)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129124 SCV000183841 uncertain significance Hereditary cancer-predisposing syndrome 2017-04-21 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (benign)
University of Washington Department of Laboratory Medicine,University of Washington RCV000210186 SCV000266191 uncertain significance Lynch syndrome 2015-11-20 criteria provided, single submitter clinical testing
Invitae RCV000688403 SCV000816013 uncertain significance Hereditary nonpolyposis colon cancer 2018-09-13 criteria provided, single submitter clinical testing This sequence change replaces asparagine with histidine at codon 477 of the MSH2 protein (p.Asn477His). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual with a family history of colon cancer (PMID: 26845104). ClinVar contains an entry for this variant (Variation ID: 140888). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 RCV000129124 SCV000911927 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-12 criteria provided, single submitter clinical testing

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