ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.2189A>G (p.Tyr730Cys) (rs587782900)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000132542 SCV000187639 uncertain significance Hereditary cancer-predisposing syndrome 2014-04-04 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Invitae RCV000475472 SCV000551173 uncertain significance Lynch syndrome 2016-09-15 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 730 of the MSH6 protein (p.Tyr730Cys). The tyrosine residue is weakly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is present in population databases (rs587782900, ExAC <0.01%). This variant has been reported in an individual affected with ovarian cancer (PMID: 23047549). ClinVar contains an entry for this variant (Variation ID: 143023). 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 tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. It has been reported in both the population and an affected individual, but the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Color RCV000132542 SCV000908255 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-18 criteria provided, single submitter clinical testing

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