ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1967A>G (p.Tyr656Cys) (rs185356145)

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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 RCV000213193 SCV000276157 uncertain significance Hereditary cancer-predisposing syndrome 2018-02-12 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or Conflicting Evidence
Invitae RCV000791407 SCV000548273 uncertain significance Hereditary nonpolyposis colon cancer 2018-12-19 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 656 of the MSH2 protein (p.Tyr656Cys). The tyrosine residue is weakly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is present in population databases (rs185356145, ExAC 0.003%) but has not been reported in the literature in individuals with a MSH2-related disease. ClinVar contains an entry for this variant (Variation ID: 232107). 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 cysteine 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.
Mendelics RCV000477485 SCV000837842 uncertain significance Lynch syndrome 2018-07-02 criteria provided, single submitter clinical testing
Color RCV000213193 SCV000906777 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-13 criteria provided, single submitter clinical testing

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