ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.899G>A (p.Arg300Gln) (rs55760494)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000199066 SCV000254336 uncertain significance Hereditary nonpolyposis colon cancer 2018-12-28 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 300 of the MSH6 protein (p.Arg300Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MSH6-related disease. ClinVar contains an entry for this variant (Variation ID: 216323). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C35"). 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 RCV000214218 SCV000274179 uncertain significance Hereditary cancer-predisposing syndrome 2017-11-28 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
GeneDx RCV000586061 SCV000279809 uncertain significance not provided 2018-02-15 criteria provided, single submitter clinical testing This variant is denoted MSH6 c.899G>A at the cDNA level, p.Arg300Gln (R300Q) at the protein level, and results in the change of an Arginine to a Glutamine (CGG>CAG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. MSH6 Arg300Gln was not observed at a significant allele frequency in large population cohorts (Lek 2016). MSH6 Arg300Gln is located in the nuclear localization signal (Gassman 2011). In-silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether MSH6 Arg300Gln is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Integrated Genetics/Laboratory Corporation of America RCV000586061 SCV000695932 uncertain significance not provided 2016-02-10 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000586061 SCV000889509 uncertain significance not provided 2018-03-08 criteria provided, single submitter clinical testing
Color RCV000214218 SCV000911931 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-12 criteria provided, single submitter clinical testing

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