ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.1169A>G (p.Tyr390Cys) (rs200928781)

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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 RCV000566309 SCV000665261 likely pathogenic Hereditary cancer-predisposing syndrome 2018-07-26 criteria provided, single submitter clinical testing
Invitae RCV000475251 SCV000550449 uncertain significance Familial cancer of breast 2018-06-24 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 390 of the CHEK2 protein (p.Tyr390Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with breast cancer as well as unaffected control individuals (PMID: 25619829). ClinVar contains an entry for this variant (Variation ID: 410015). Experimental studies have shown that when expressed in CHEK2-deficient mouse cells, CHEK2 protein containing this missense change did not rescue cell cycle check point activation and apoptotic response to DNA damage (PMID: 25619829). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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