ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.2158A>G (p.Lys720Glu) (rs747265823)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000214268 SCV000276867 uncertain significance Hereditary cancer-predisposing syndrome 2017-04-18 criteria provided, single submitter clinical testing In silico models in agreement (deleterious) and/or completely conserved position in appropriate species;Insufficient or conflicting evidence
Invitae RCV000524727 SCV000625356 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-09-01 criteria provided, single submitter clinical testing This sequence change replaces lysine with glutamic acid at codon 720 of the MSH2 protein (p.Lys720Glu). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamic acid. This variant is present in population databases (rs747265823, ExAC 0.02%). This variant has not been reported in the literature in individuals with a MSH2-related disease. ClinVar contains an entry for this variant (Variation ID: 232677). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant has uncertain impact on MSH2 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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