ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.2420C>G (p.Thr807Ser) (rs41295294)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000627714 SCV000284151 uncertain significance Hereditary nonpolyposis colon cancer 2017-09-13 criteria provided, single submitter clinical testing This sequence change replaces threonine with serine at codon 807 of the MSH2 protein (p.Thr807Ser). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with colorectal cancer (PMID: 18033691) and in a study of Swedish families affected Lynch syndrome (PMID: 27601186). ClinVar contains an entry for this variant (Variation ID: 90968). General algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD), as well as an algorithm developed specifically for mismatch repair genes (PMID: 22290698), all suggest that this variant is likely to be tolerated. The serine 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.
Ambry Genetics RCV000573758 SCV000669834 uncertain significance Hereditary cancer-predisposing syndrome 2017-01-12 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence,In silico models in agreement (benign)

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