ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.2975A>G (p.Glu992Gly) (rs876660688)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000219717 SCV000278320 uncertain significance Hereditary cancer-predisposing syndrome 2015-09-14 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Insufficient or conflicting evidence
GeneKor MSA RCV000219717 SCV000822065 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing
Color RCV000219717 SCV000904826 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-02 criteria provided, single submitter clinical testing
Invitae RCV000792117 SCV000931395 uncertain significance Hereditary nonpolyposis colon cancer 2018-12-25 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with glycine at codon 992 of the MSH6 protein (p.Glu992Gly). The glutamic acid residue is moderately conserved and there is a moderate physicochemical difference between glutamic acid and glycine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a MSH6-related disease. 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 C15"). The glycine amino acid residue is also 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 novel 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.

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