ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.3598A>G (p.Ile1200Val) (rs781627838)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000791410 SCV000261536 uncertain significance Hereditary nonpolyposis colon cancer 2018-12-26 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 1200 of the MSH6 protein (p.Ile1200Val). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs781627838, ExAC 0.006%). This variant has not been reported in the literature in individuals with MSH6-related disease. ClinVar contains an entry for this variant (Variation ID: 220745). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but 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 RCV000566750 SCV000662446 uncertain significance Hereditary cancer-predisposing syndrome 2017-06-07 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Mendelics RCV000204738 SCV000837918 uncertain significance Lynch syndrome 2018-07-02 criteria provided, single submitter clinical testing

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