ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.2718A>G (p.Ile906Met) (rs876659835)

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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 RCV000216683 SCV000276710 uncertain significance Hereditary cancer-predisposing syndrome 2015-06-24 criteria provided, single submitter clinical testing Rarity in general population databases (dbsnp, esp, 1000 genomes);Insufficient or conflicting evidence;In silico models in agreement (benign)
Invitae RCV000459524 SCV000548285 uncertain significance Lynch syndrome 2016-10-21 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with methionine at codon 906 of the MSH2 protein (p.Ile906Met). The isoleucine residue is weakly conserved and there is a small physicochemical difference between isoleucine and methionine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a MSH2-related disease. ClinVar contains an entry for this variant (Variation ID: 232549). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). The methionine 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. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Color RCV000216683 SCV001345630 uncertain significance Hereditary cancer-predisposing syndrome 2019-12-16 criteria provided, single submitter clinical testing

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