ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.1011C>A (p.Tyr337Ter) (rs760502479)

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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 RCV000164779 SCV000215455 pathogenic Hereditary cancer-predisposing syndrome 2017-07-11 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
GeneDx RCV000424411 SCV000516126 pathogenic not provided 2017-10-23 criteria provided, single submitter clinical testing This pathogenic variant is denoted CHEK2 c.1011C>A at the cDNA level and p.Tyr337Ter (Y337X) at the protein level. The substitution creates a nonsense variant, which changes a Tyrosine to a premature stop codon (TAC>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in at least one individual undergoing multi-gene panel testing (LaDuca 2017). This variant is considered pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000424411 SCV000601139 pathogenic not provided 2017-07-20 criteria provided, single submitter clinical testing
Invitae RCV000532130 SCV000633081 pathogenic Familial cancer of breast 2018-12-28 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr337*) in the CHEK2 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs760502479, ExAC 0.002%). This variant has not been reported in the literature in individuals with CHEK2-related disease. ClinVar contains an entry for this variant (Variation ID: 185370). Loss-of-function variants in CHEK2 are known to be pathogenic (PMID: 21876083, 24713400). For these reasons, this variant has been classified as Pathogenic.

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