ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.806C>G (p.Thr269Ser) (rs587779322)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000684794 SCV000551228 uncertain significance Hereditary nonpolyposis colon cancer 2018-06-15 criteria provided, single submitter clinical testing This sequence change replaces threonine with serine at codon 269 of the MSH6 protein (p.Thr269Ser). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and serine. This variant is present in population databases (rs587779322, ExAC 0.006%). This variant has been observed in individuals with suspected Lynch syndrome (PMID: 22495361). ClinVar contains an entry for this variant (Variation ID: 89568). An algorithm developed specifically for the MSH6 gene suggests that this missense change is likely to be tolerated (PMID: 23621914). However, this prediction has not been confirmed by published functional studies and its clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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 RCV000568144 SCV000673934 uncertain significance Hereditary cancer-predisposing syndrome 2018-03-22 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759873 SCV000889507 uncertain significance not provided 2017-09-15 criteria provided, single submitter clinical testing

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