ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.759G>A (p.Met253Ile) (rs1060502021)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000467943 SCV000548266 uncertain significance Hereditary nonpolyposis colon cancer 2018-12-02 criteria provided, single submitter clinical testing This sequence change replaces methionine with isoleucine at codon 253 of the MSH2 protein (p.Met253Ile). The methionine residue is weakly conserved and there is a small physicochemical difference between methionine and isoleucine. This variant is not present in population databases (ExAC no frequency). 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: 408527). 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 isoleucine 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 and their clinical significance is uncertain. 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.
Ambry Genetics RCV000568397 SCV000662257 uncertain significance Hereditary cancer-predisposing syndrome 2016-10-18 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000568397 SCV000904248 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-15 criteria provided, single submitter clinical testing

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